Bladder Cancer

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Care of the Urothelial Cancer Patient and Prospective Collection of Biospecimens From Healthy Volunteers and Urothelial Cancer Patients


Condition: Bladder Cancer, Urinary Tract Cancer, Urothelial Cancer, Healthy Volunteers

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT02379429

Sponsor: National Cancer Institute (NCI)

Phase:

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • FOR UROTHELIAL CANCER PARTICIPANTS:
  • Adults (>= 18 years of age) with biopsy-proven or suspected urothelial cancer who require and are willing to undergo diagnostic or therapeutic intervention as part of their diagnosis, standard of care treatment, or follow-up/surveillance for their neoplasm.
  • ECOG performance status of 0-3.
  • Must be willing and able to provide informed consent. EXCLUSION CRITERIA:
  • Subjects who are pregnant.
  • Subjects co-morbidities preclude diagnostic or therapeutic intervention. Co-morbidities include: --Ongoing treatment for another non-skin malignancy.
  • History of hepatitis B/C or HIV. Patients who are HIV positive are excluded from this study because treatment with immunomodulatory agents for immunosuppressed patients would affect sample analysis and skew the data. ELIGIBILITY CRITERIA FOR HEALTHY VOLUNTEERS INCLUSION CRITERIA: -Adults (greater than or equal to 18 years of age) and able to give informed consent.

Exclusion Criteria:

  • Subjects who are pregnant.
  • Subjects co-morbidities preclude diagnostic or therapeutic intervention. Co-morbidities include: --Ongoing treatment for another non-skin malignancy.
  • History of hepatitis B/C or HIV. Patients who are HIV positive are excluded from this study because treatment with immunomodulatory agents for immunosuppressed patients would affect sample analysis and skew the data.

Eligibility Criteria:

  • FOR HEALTHY VOLUNTEERS INCLUSION CRITERIA: -Adults (greater than or equal to 18 years of age) and able to give informed consent. EXCLUSION CRITERIA:
  • Subjects who are pregnant.
  • Diagnosis of cancer requiring treatment other than minor resection of basal cell or squamous cell skin cancers.
  • Heart, lung, kidney disease, or other medical conditions as per Principal Investigator discretion.
  • History of acute or chronic hepatitis B/C or HIV infection. Patients who are HIV positive are excluded from this study because treatment with immunomodulatory agents for immunosuppressed patients would affect sample analysis and skew the data.
  • Healthy volunteers who are family members with germline mutations.

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Adding Mitomycin to Bacillus of Calmette-Guerin (BCG) as Adjuvant Intravesical Therapy for High-risk, Non-Muscle-invasive Bladder Cancer: a Randomised Phase 3 Trial


Condition: Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02948543

Sponsor: University of Sydney

Phase: Phase 3

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  1. Males or females with confirmed high grade pTa or stage pT1 (any grade) non-muscle invasive bladder cancer on initial or re-resection histology (concurrent carcinoma in situ is allowed).
  2. Age >= 18 yrs
  3. No macroscopically visible disease at cystoscopy within 8 weeks prior to randomisation. This may be either the initial Transurethral Resection of the Bladder Tumour (TURBT) at which the primary tumour was completely resected, or a planned second cystoscopy and/or re-resection done within 8 weeks of the initial TURBT.
  4. ECOG Performance Status of 0-2
  5. Adequate bone marrow, renal and liver function confirmed by pre-randomisation blood tests.
  6. Study treatment both planned and able to start within 4 weeks of randomisation
  7. Has completed the HRQL questionnaires or is unable to complete them because of literacy, insufficient English or limited vision
  8. Willing and able to comply with all study requirements, including treatment, timing and/or nature of all required assessments
  9. Signed, written informed consent

Exclusion Criteria:

  1. Contraindications or hypersensitivity to investigational products, BCG and Mitomycin
  2. Prior treatment with any other intravesical agent including BCG or Mitomycin (excludes single doses given post TURBT)
  3. Current or past transitional cell carcinoma (TCC) of the upper urinary tract
  4. Prior muscle-invasive (stage T2 or higher) transitional-cell carcinoma of the bladder
  5. Bladder dysfunction precluding intravesical therapy eg. Severe urinary incontinence or overactive or spastic bladder
  6. Life expectancy < 3 months
  7. Congenital or acquired immune deficiencies, whether due to a concurrent disease (e.g. acquired immune deficiency syndrome (AIDS), leukaemia, lymphoma) or immunosuppressive therapy (e.g. corticosteroids), or cancer therapy (cytotoxic drugs, radiation)
  8. Prior radiotherapy of the pelvis
  9. Prior or current treatment with radiotherapy-response or biological-response modifiers
  10. Clinical evidence of existing active tuberculosis
  11. History of another malignancy within 5 years prior to registration. Patients with non-melanomatous carcinoma of the skin are eligible for this study.
  12. Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol.
  13. Pregnancy, lactation, or inadequate contraception. Women must be post menopausal, infertile, or use a reliable means of contraception. Women of childbearing potential must have a negative pregnancy test done within 7 days prior to registration. Men must have been surgically sterilised or use a (double if required) barrier method of contraception.

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Optimized Perioperative Antibiotic Prophylaxis in Radical Cystectomy


Condition: Radical Cystectomy, Surgical Site Infection, Urologic Cancer, Perioperative/Postoperative Complications, Antibiotic Resistant Infection, Antibiotic Side Effect, Antibiotic-associated Diarrhea

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03305627

Sponsor: University Hospital Inselspital, Berne

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Written informed consent
  • Age >18 years
  • Planned radical cystectomy at the Department of Urology, Bern University Hospital

Exclusion Criteria:

  • Contraindications to the classes of drugs under study, e.g. known hypersensitivity or allergy to class of drugs including alternatives described in the protocol or the investigational product,
  • Women who are pregnant or breast feeding (exclusion for surgery),
  • Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant,
  • Previous enrolment into the current study,
  • Enrolment of the investigator, his/her family members, employees and other dependent persons,

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Intravesical Mistletoe Extract in Superficial Bladder Cancer: A Phase III Efficacy Study


Condition: Superficial Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02106572

Sponsor: Abnoba Gmbh

Phase: Phase 3

Eligibility:

  • Age: minimum 18 Years maximum 85 Years
  • Gender: All

Inclusion Criteria:

  • Signed and dated written informed consent for data protection and willingness to participate and comply with the study protocol prior to any study-related procedures
  • Completely resected (detrusor muscle in the TUR specimen according to need) superficial bladder carcinoma (Stage Ta) with classification as intermediate-risk according to the EAU (update 2013) and one immediately post operative intravesical MMC instillation of 40 mg, completed re-resection if indicated
  • Karnofsky Performance Status of 50% to 100% (corresponding to Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2)
  • Life expectancy of ≥ 2 years at the time point of study inclusion
  • Normal renal and liver function, normal cardiac and hematology profiles (patients with laboratory values slightly outside the reference range may be included, unless the investigator considers the abnormality as clinically significant)
  • Female patients of childbearing potential must have a negative pregnancy test (β-human chorionic gonadotropin test) at Screening. Pregnancy during the treatment period including 12 weeks after the last instillation has to be excluded

Exclusion Criteria:

  • Locally infiltrative or metastatic bladder tumor (Stage T2 or greater), low-risk Ta tumor (primary, solitary, LG/G1, <3 cm, no CIS) or high-risk tumors according to EAU classification, update 2013 (T1; HG/G3; CIS; multiple and recurrent and large [>3 cm] Ta G1/G2 tumors [all conditions must be present at this point], presence of upper urinary tract tumors or lesions which were not completely removed by TURB
  • Urinary tract infection, benign prostatic obstruction grade II or III, neurogenic bladder, stress incontinence, bladder or urethral diverticula, fistulas or urethral stenosis
  • Patients with acute systemic illness, such as inflammatory infections with fever > 38°C
  • Patients with previous recurrence of a superficial bladder cancer or radiotherapy of the bladder or other intravesical treatment within the last 6 months, or patients with previous mistletoe therapy
  • Patients with other previous or co-existing malignancies or CIS
  • Patients having any previous or concurrent therapy with a systemic chemo- / immunotherapeutical treatment regimen, in particular vinca alkaloids, bleomycine and doxorubicine, or patients who are treated with pyroxidine hydrochloride (vitamin B6)
  • Untreated coagulation disorders or inadequate anticoagulation therapy
  • Leukocyte count < 4,000/mm3 or platelet count < 100,000/mm3
  • Serum creatinine > 1.7 mg/dL
  • Patients with known hypersensitivity to the excipients of the study medication (monosodium phosphate, disodium phosphate, ascorbic acid)
  • Patients with a known hypersensitivity to mistletoe products and MMC
  • Patients who were administered within a 4-week period before Visit 1 any other experimental drug under investigation
  • Male patients planning to father a child or sperm donation from the first administration of study medication until 3 months after the last administration of the study medication
  • Male patients unwilling to use barrier contraception ie, condoms and spermicide, from the day of first administration of the study medication until 12 weeks after administration of the study medication. In case the sexual relation is restricted to women fulfilling one of the criteria listed under inclusion criteria for female patients the barrier contraception is not necessary.
  • Patients with a history of alcohol and / or drug abuse
  • Patients who are unable to be regularly observed, not permitting adequate follow-up and compliance to the protocol

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DART: Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors


Condition: Acinar Cell Carcinoma, Adenoid Cystic Carcinoma, Adrenal Cortical Carcinoma, Adrenal Gland Pheochromocytoma, Anal Canal Neuroendocrine Carcinoma, Anal Canal Undifferentiated Carcinoma, Angiosarcoma, Apocrine Neoplasm, Appendix Mucinous Adenocarcinoma, Bartholin Gland Transitional Cell Carcinoma, Basal Cell Carcinoma, Bladder Adenocarcinoma, Breast Metaplastic Carcinoma, Cervical Adenocarcinoma, Cholangiocarcinoma, Chordoma, Colorectal Squamous Cell Carcinoma, Desmoid Fibromatosis, Endometrial Transitional Cell Carcinoma, Endometrioid Adenocarcinoma, Esophageal Neuroendocrine Carcinoma, Esophageal Undifferentiated Carcinoma, Extrahepatic Bile Duct Carcinoma, Extramammary Paget Disease, Fallopian Tube Adenocarcinoma, Fallopian Tube Transitional Cell Carcinoma, Fibromyxoid Tumor, Gallbladder Carcinoma, Gastric Neuroendocrine Carcinoma, Gastric Squamous Cell Carcinoma, Gastric Undifferentiated Carcinoma, Gastrointestinal Stromal Tumor, Gestational Trophoblastic Tumor, Giant Cell Carcinoma, Human Papillomavirus-Independent Cervical Adenocarcinoma, Clear Cell-Type, Intestinal Neuroendocrine Carcinoma, Intrahepatic Cholangiocarcinoma, Lung Carcinoid Tumor, Lung Sarcomatoid Carcinoma, Major Salivary Gland Carcinoma, Malignant Odontogenic Neoplasm, Malignant Peripheral Nerve Sheath Tumor, Malignant Solid Neoplasm, Malignant Testicular Sex Cord-Stromal Tumor, Metastatic Malignant Neoplasm of Unknown Primary, Metastatic Pituitary Neuroendocrine Tumor, Minimally Invasive Lung Adenocarcinoma, Mixed Mesodermal (Mullerian) Tumor, Mucinous Adenocarcinoma, Mucinous Cystadenocarcinoma, Nasal Cavity Adenocarcinoma, Nasal Cavity Carcinoma, Nasopharyngeal Carcinoma, Nasopharyngeal Papillary Adenocarcinoma, Nasopharyngeal Undifferentiated Carcinoma, Oral Cavity Carcinoma, Oropharyngeal Undifferentiated Carcinoma, Ovarian Adenocarcinoma, Ovarian Germ Cell Tumor, Ovarian Mucinous Adenocarcinoma, Ovarian Squamous Cell Carcinoma, Ovarian Transitional Cell Carcinoma, Pancreatic Acinar Cell Carcinoma, Pancreatic Neuroendocrine Carcinoma, Paraganglioma, Paranasal Sinus Adenocarcinoma, Paranasal Sinus Carcinoma, Parathyroid Gland Carcinoma, PEComa, Peritoneal Mesothelioma, Placental Choriocarcinoma, Primary Peritoneal High Grade Serous Adenocarcinoma, Pseudomyxoma Peritonei, Rare Disorder, Scrotal Squamous Cell Carcinoma, Seminal Vesicle Adenocarcinoma, Seminoma, Serous Cystadenocarcinoma, Small Intestinal Adenocarcinoma, Small Intestinal Squamous Cell Carcinoma, Spindle Cell Neoplasm, Squamous Cell Carcinoma of the Penis, Teratoma With Somatic-Type Malignancy, Testicular Non-Seminomatous Germ Cell Tumor, Thyroid Gland Carcinoma, Tracheal Carcinoma, Transitional Cell Carcinoma, Ureter Adenocarcinoma, Ureter Squamous Cell Carcinoma, Urethral Adenocarcinoma, Urethral Squamous Cell Carcinoma, Vaginal Adenocarcinoma, Vaginal Squamous Cell Carcinoma, Not Otherwise Specified, Vulvar Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02834013

Sponsor: National Cancer Institute (NCI)

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Patients are eligible under ONE of the following criteria:
  • For all cohorts except the gestational trophoblastic disease (GTD) (Cohort #47), patients must have histologically and/or biochemically confirmed rare cancer and must be able to submit specimens; to be eligible for the GTD cohort: patients must have disease confirmed by quantitative serum beta-human chorionic gonadotropin (hCG) within 28 days prior to registration and must be able to submit blood specimens (tissue submission is not required for patients who will be registered to the GTD cohort [Cohort #47]); NOTE: Subsequent to site's Institutional Review Board (IRB) approval of revision 3, patients are NOT required to participate in EAY131 "National Cancer Institute (NCI)-Molecular Analysis for Therapy Choice (MATCH)" to register to S1609 OR
  • FOR PATIENTS WITH PD-L1 AMPLIFICATION (COHORT #50) ONLY: All solid tumors (excluding lymphoma) are allowed for the PD-L1 amplified cohort if they have PD-L1 amplification; patients may be considered for registration to the PD-L1 amplified cohort (Cohort #50) with the confirmation of at least one of the study chairs; PD-L1 amplification is defined as having deoxyribonucleic acid (DNA) copy number of equal to or greater than six by any of the following Clinical Laboratory Improvement Act (CLIA)-approved lab; (Immunohisochemistry [IHC] and fluorescence in situ hybridization [FISH] are not allowed); the assay must be done at or after the diagnosis of advanced disease, but PRIOR TO REGISTRATION; NOTE: patients with PD-L1 overexpression by IHC or PD-L1 amplification by FISH do not quality for this cohort; OR
  • FOR PATIENTS ENROLLED IN EAY131 "NCI-MATCH" PRIOR TO EAY131 ADDENDUM 10 ONLY: Patients must have histologically confirmed rare cancer that did not have a match to a molecularly-guided therapy on EAY131 "NCI-MATCH" protocol or who are off protocol treatment on EAY131, "NCI-MATCH" and have no further molecularly-matched treatment recommendations per EAY131, "NCI-MATCH" or who are otherwise unable to receive EAY131, "NCI-MATCH" therapy
  • Patients who do not qualify for one of the histologic cohorts and are not on the ineligible histology list may be considered for registration in the "Not Otherwise Categorized" Rare Tumors cohort with confirmation of at least one of the study chairs via email
  • NOTE: The "Not Otherwise Categorized" Rare Tumors cohort was permanently closed to accrual on 3/15/2019
  • Patients who are determined to have a rare cancer with unknown primary site are eligible under cohort #32 (tumor of unknown primary [cancer of unknown primary; CuP]), provided that there is histologic documentation of metastatic malignancy with no discernible primary site identified from histopathologic review, physical exam and associated cross-sectional imaging of the chest, abdomen, and pelvis
  • NOTE: The "Tumor of unknown primary (Cancer of Unknown Primary; CuP" cohort was permanently closed to accrual on 12/22/2017
  • Patients must also meet one of the following:
  • Patients must have progressed following at least one line of standard systemic therapy and there must not be other approved/standard therapy available that has been shown to prolong overall survival (i.e. in a randomized trial against another standard treatment or by comparison to historical controls); patients who cannot receive other standard therapy that has been shown to prolonged survival due to medical issues will be eligible, if other

Eligibility Criteria:

  • are met; OR
  • Patients for whose disease no standard treatment exists that has been shown to prolong overall survival
  • For all cohorts except the GTD cohort (Cohort #47): Patients must have a diagnostic quality computed tomography (CT) scan or magnetic resonance imaging (MRI), performed within 28 days prior to registration, which demonstrates measurable disease, as defined in RECIST v. 1.1; scans must include imaging of the chest, abdomen and pelvis, with the exception of patients with head/neck cancer, who must have imaging of the chest, abdomen, pelvis and neck; if there is clinical suspicion for bone metastases at the time of enrollment (in the judgement of the treating investigator) bone scan should be performed; bone scans done within 42 days prior to registration may be used to establish baseline condition at registration
  • No other prior malignancy is allowed except for the following:
  • Adequately managed stage I or II cancer from which the patient is currently in complete remission
  • Any other cancer from which the patient has been disease free for one year
  • Adequately managed stage I or II follicular thyroid or prostate cancer is also eligible, wherein patient is not required to be in complete remission
  • Note: Second primary tumors are not allowed concurrent with any of the eligible rare cancers
  • For all cohorts except the PD-L1 amplified tumors cohort (Cohort # 50): Patients may have received either prior anti-CTLA4 or other prior anti-PD-1/anti-PD-L1 therapy, but not both, provided that it is completed >= 4 weeks prior to registration. To be eligible for the PD-L1 amplified tumors cohort (Cohort #50): Patients must not have received anti-PD-1/anti-PD-L1 therapy; prior anti-CTLA-4 is allowed provided that it is completed >= 4 weeks prior to registration
  • Patients with clinically controlled thyroiditis or pituitary disorders on stable replacement therapy are eligible
  • Patients with autoimmune disease who are otherwise eligible must not have received steroid and immunosuppressive therapy within 28 days prior to registration
  • Patients with brain metastases or primary brain tumors must have completed treatment, surgery or radiation therapy >= 28 days prior to registration and have stable disease at time of registration; these patients must also have a CT or MRI of the brain to evaluate for CNS disease within 42 days prior to registration to S1609; metastatic brain parenchymal disease must have been treated and patient must be off steroids for 7 days prior to registration
  • Hormonal or endocrine blockade is permitted as long as patient has demonstrated progression on prior therapy (e.g. gonadotrophin releasing hormone [GnRH], somatostatin); long-acting somatostatin analogs (including octreotide) and androgen deprivation treatment (including long-acting leuprolide) are permitted while on protocol therapy
  • Patients must have a Zubrod performance status of 0-2
  • Absolute neutrophil count (ANC) >= 1,000/mcL (within 28 days prior to registration)
  • Platelets >= 75,000/mcL (within 28 days prior to registration)
  • Hemoglobin >= 8 g/dL (within 28 days prior to registration)
  • Total bilirubin =< 2.0 x institutional upper limit of normal (IULN) or for documented/suspected Gilbert's disease, total bilirubin =< 3.0 x IULN (within 28 days prior to registration)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) both =< 3 x IULN (within 28 days prior to registration)
  • Serum creatinine =< 2.0 x IULN (within 28 days prior to registration)
  • Creatinine clearance (CrCl) >= 50 mL/min., as estimated by the Cockcroft and Gault formula; estimated creatinine clearance is based on actual body weight (within 28 days prior to registration)
  • Patients must have adequate thyroid function, as evidenced by either thyroid-stimulating hormone (TSH) or, free thyroxine (T4) serum tests demonstrating values within the normal range, within 28 days prior to registration; at pre-registration, if TSH is not within normal limits, then free T4 must be performed and must be within normal range for patient to be eligible; Note: TSH, with reflex T4 (if TSH is abnormal) is allowable if per institutional standard, provided that free T4 is within normal range; patients who have undergone thyroidectomy or who are on thyroid suppression for their cancer are not required to have normal TSH and free T4
  • Patients must have adequate adrenal axis function, as evidenced by cortisol levels within institutional normal ranges (ante meridiem [AM] cortisol preferred), OR adrenocorticotropic hormone (ACTH) values within the institutional normal ranges within 28 days prior to registration; if cortisol levels are not within normal limits prior to registration, then ACTH must be performed and must be within normal ranges for patient to be eligible; Note: Neither cortisol nor ACTH levels are required for patients with primary adrenal tumors (e.g. adrenocortical carcinoma)
  • For women of childbearing potential, the local investigator must rule out pregnancy; Except for Cohorts 13 and 47, where tumor types may express beta-hCG, women of childbearing potential must have a serum or urine pregnancy test within 7 days prior to registration; for Cohorts 13 and 47, where tumor types may produce hCG (e.g. germ cell tumors or trophoblastic disease), other pregnancy exclusion methods should be used to rule out pregnancy, such as ultrasound examination, documented history of effective contraception, or documented infertility; all females of childbearing potential must have been demonstrated not to be pregnant within 7 days prior to registration and agree to use birth control throughout study and for 23 weeks after completion of protocol therapy; patients must not be pregnant or nursing due to risk of fetal or nursing infant harm; women of childbearing potential must have agreed to use an effective contraceptive method; a woman is considered to be of "childbearing potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, she is responsible for beginning contraceptive measures
  • Men of reproductive potential must have agreed to use birth control throughout the study and for 31 weeks after completion of protocol therapy; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (vasectomy); however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he is responsible for beginning contraceptive measures
  • Patients who are known to be human immunodeficiency virus (HIV)-positive at registration are eligible at the time of registration:
  • CD4+ cell count greater or equal to 250 cells/mm^3
  • No history of non-malignancy acquired immunodeficiency syndrome (AIDS)-defining conditions other than historical low CD4+ cell counts
  • Patients must have amylase or lipase within =< 1.5 x IULN without symptoms of pancreatitis at registration, within 28 days prior to registration
  • Patients must have fully recovered from any adverse effects of major surgery (to =< grade 1) at least 14 days prior to registration

Exclusion Criteria:

  • Patients who had prior grade 3 or higher immune-related adverse event (e.g. pneumonitis, hepatitis, colitis, endocrinopathy) with prior immunotherapy (e.g. cancer vaccine, cytokine, etc.) are not eligible
  • Patients are not eligible if they have had or are planned for solid organ transplant
  • Patients must not currently be receiving any other investigational agents or any other systemic anti-cancer therapy (including radiation, excluding RANKL inhibitors and bisphosphonates); in event patient recently received any other systemic anti-cancer therapy, patient must be off therapy at least 7 days prior to registration and any therapy-induced toxicity must have recovered to =< grade 1, except alopecia and =< grade 2 neuropathy which are allowed; any planned radiation therapy must be completed before registration to S1609
  • Patients must not have prior history of allergy or known hypersensitivity to nivolumab or ipilimumab
  • Patients must not have known active hepatitis B virus (HBV) or hepatitis virus (HCV) infection at time of registration; patients with HBV or HCV that have an undetectable viral load and no residual hepatic impairment are eligible
  • Patients must not have active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, immunosuppressive drugs, or corticosteroids with prednisone dose >= 10 mg); replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment; autoimmune diseases include but are not limited to autoimmune hepatitis, inflammatory bowel disease (including ulcerative colitis and Crohn's disease), as well as symptomatic disease (e.g.: rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener's granulomatosis]); central nervous system (CNS) or motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre syndrome and Myasthenia gravis, multiple sclerosis or glomerulonephritis); vitiligo, alopecia, hypothyroidism on stable doses of thyroid replacement therapy, psoriasis not requiring systemic therapy within the past 2 years is permitted; short-term steroid premedication for contrast allergy is permitted
  • Patients must not have any uncontrolled intercurrent illness including (not limited to): symptomatic congestive heart failure (CHF) (New York Heart Association [NYHA] III/IV), unstable angina pectoris or coronary angioplasty, or stenting within 24 weeks prior to registration, unstable cardiac arrhythmia (ongoing cardiac dysrhythmias of NCI Common Terminology Criteria for Adverse Events [CTCAE] version [v] 4 grade >= 2), known psychiatric illness that would limit study compliance, intra-cardiac defibrillators, known cardiac metastases, or abnormal cardiac valve morphology (>= grade 3)
  • Note: Patients with history of CHF or patients who are deemed at risk because of underlying cardiovascular disease or exposure to cardiotoxic drugs should have an electrocardiogram (EKG) and echocardiogram (ECHO), as clinically indicated, at baseline and at the start of each cycle; patients who have evidence at baseline (or subsequently) of CHF, myocardial infarction (MI), cardiomyopathy, or myositis cardiac evaluation (NYHA I/II) should have additional consult by a cardiologist, including review of EKG, creatine phosphokinase (CPK), troponin, echocardiogram, as clinically indicated
  • Patients must not have symptomatic interstitial lung disease or pneumonitis

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A Phase II Study of Olaparib (AZD2281) in Patients With Metastatic/Advanced Urothelial Carcinoma and Other Genitourinary Tumors With DNA-Repair Defects


Condition: Advanced Bladder Carcinoma, Advanced Genitourinary System Carcinoma, Metastatic Bladder Carcinoma, Metastatic Genitourinary System Carcinoma, Stage III Bladder Cancer AJCC v8, Stage IV Bladder Cancer AJCC v8

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03375307

Sponsor: National Cancer Institute (NCI)

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Patients must have a histologically confirmed diagnosis non-prostate GU cancer
  • Patients must have Clinical Laboratory Improvement Act (CLIA) testing and fit one of the following groups:
  • Confirmed presence of a cancer-associated alteration considered pathogenic/likely pathogenic by FM and/or the Genetics Review Panel in one or more of the following genes: BRCA1, BRCA2, ATM, BAP1, MSH2, PALB2, and BRIP1 or in one or more of the DNA-repair genes tested in the FoundationOne FoundationOneCDx (F1CDx) panel including the following genes (Foundation One mutation analysis results performed prior to enrollment on this study may be accepted for eligibility review and in the event that a patient cannot undergo a biopsy and tumor is not available, Foundation Medicine liquid biopsy may be performed): ABL1, ATR, ATRX, BARD1, BRD4, CCND1, CHEK1, CHEK2, DOT1L, FANCC, FANCE, FANCG, FANCL, IKBKE, MEN1, MLH1, MSH2, MSH6, MUTYH, NPM1, PMS2, POLD1, POLE, RAD51, SMARCB1, STK11, TP53
  • Note: FoundationOneCDx (F1CDx) is a next generation sequencing based in vitro diagnostic device for detection of substitutions, insertion and deletion alterations (indels), and copy number alterations (CNAs) in 324 genes and select gene rearrangements, as well as genomic signatures including microsatellite instability (MSI) and tumor mutational burden (TMB) using DNA isolated from formalin-fixed paraffin embedded (FFPE) tumor tissue specimens
  • Patients with benign or variants of unknown significance as determined by FoundationOne FoundationOneCDx (F1CDx) panel and Genetics Review Panel review will be included to be followed for survival
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm (>= 2 cm) by chest x-ray or as >= 10 mm (>= 1 cm) with computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
  • Evidence of disease progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1) during treatment or after the most recent dose of therapy with at least one platinum-based regimen of chemotherapy and/or an immune-checkpoint inhibitor (atezolizumab, pembrolizumab, nivolumab, avelumab or durvalumab) (2-week washout from chemotherapy and 4-weeks washout from monoclonal antibodies is required)
  • Age >= 18 years. Because no dosing or adverse event data are currently available on the use of olaparib in patients < 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (or Karnofsky >= 70%)
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) (for subjects with documented Gilbert's disease total bilirubin =< 3.0 mg/dL)
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal (for subjects with liver metastasis AST/ALT =< 5 x ULN)
  • Creatinine clearance >= 50 mL/min/1.73 m^2
  • Hemoglobin >= 10 g/dL; transfusions are allowed
  • Prothrombin time (PT)/international normalized ratio (INR) and activated partial thromboplastin time (aPTT) within 1.25 x ULN institutional limits, except where a lupus anti-coagulant has been confirmed or the patient is on direct oral anticoagulant (DOA)
  • Patients must be able to tolerate oral medications and not have gastrointestinal illnesses that would preclude absorption of olaparib
  • Pre-clinical data indicate that olaparib adversely affects embryofetal survival and development. Therefore, women of child-bearing potential and their partners should agree to use two (2) highly effective forms of contraception throughout study participation and for at least one (1) month after the last dose of olaparib. Male study participants should avoid fathering a child or donating sperm during the study and for three (3) months after the last dose of olaparib.
  • Note: Olaparib is a PARP inhibitor with the potential for teratogenic or abortifacient effects. Because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with olaparib, breastfeeding should be discontinued if the mother is treated with olaparib
  • Ability to understand and the willingness to sign a written informed consent document or patients with impaired decision making capacity (IDMC) if they are represented by a legally authorized representative (LAR)
  • Patients must provide archival tumor sample for mutation analysis or be willing to undergo mandatory screening biopsy. In the event that the patient cannot undergo biopsy and tumor is not available, Foundation Medicine liquid biopsy will be performed
  • Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1. Postmenopausal is defined as:
  • Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments
  • Luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the post menopausal range for women under 50
  • Radiation-induced oophorectomy with last menses > 1 year ago
  • Chemotherapy-induced menopause with > 1 year interval since last menses
  • Surgical sterilization (bilateral oophorectomy or hysterectomy)
  • Patients is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations

Exclusion Criteria:

  • Patients who have had prior treatment with olaparib or any other PARP inhibitor (PARPi)
  • Patients with myelodysplastic syndrome/acute myeloid leukemia; or baseline features suggestive of myelodysplastic syndrome or acute myelogenous leukemia on peripheral blood smear or bone marrow biopsy, if clinically indicated
  • Persistent toxicities (>= Common Terminology Criteria for Adverse Events [CTCAE] grade 2) with the exception of alopecia, caused by previous cancer therapy
  • Patients who are receiving any other investigational agents. Patients may be on other clinical trials or treatment during screening to determine eligibility
  • Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. A scan to confirm the absence of brain metastases is not required. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition of olaparib
  • Patients receiving any medications or substances that are inhibitors or inducers of CYP3A are ineligible. A washout period prior to starting olaparib for patients on CYP3A inhibitors is 2 weeks; and the required washout period for CYP3A inducers is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents
  • Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference texts such as the Physicians' Desk Reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
  • Pregnant women are excluded from this study because olaparib is a PARP inhibitor agent with the potential for teratogenic or abortifacient effects
  • Any chronic or concurrent acute liver disease
  • History of stroke, transient ischemic attack (TIA), or myocardial infarction, within 6 months prior to enrollment
  • Uncontrolled concurrent disease or illness including but not limited to:
  • Ongoing or active infection
  • Symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmia
  • Unstable or untreated cardiac conditions or ejection fraction of < 50% as determined by echocardiogram (ECHO) or multiple gated acquisition scan (MUGA)
  • Uncontrolled diabetes mellitus
  • Psychiatric illness/social situations that would limit compliance with study requirements
  • Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or that may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for the study
  • Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV)
  • Patients with known active hepatitis (i.e., hepatitis B or C) due to risk of transmitting the infection through blood or other body fluids
  • Other malignancy within the last 5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS), stage 1, grade 1 endometrial carcinoma, or other solid tumors including lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for >= 5 years. Patients with a history of localized triple negative breast cancer or localized resected prostate cancer may be eligible, provided they completed their adjuvant chemotherapy more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease
  • Resting electrocardiogram (ECG) with corrected QT (QTc) > 470 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome
  • Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 2 weeks prior to study treatment
  • Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery
  • Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT)

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A Randomized Phase II Study of Atezolizumab (MPDL3280A) Plus Recombinant Human IL7 (CYT107) in Patients With Locally Advanced or Metastatic Urothelial Carcinoma


Condition: Advanced Bladder Urothelial Carcinoma, Advanced Ureter Urothelial Carcinoma, Metastatic Bladder Urothelial Carcinoma, Metastatic Renal Pelvis Urothelial Carcinoma, Metastatic Ureter Urothelial Carcinoma, Metastatic Urethral Urothelial Carcinoma, Metastatic Urothelial Carcinoma, Recurrent Bladder Urothelial Carcinoma, Recurrent Renal Pelvis Urothelial Carcinoma, Recurrent Ureter Urothelial Carcinoma, Recurrent Urethral Urothelial Carcinoma, Stage III Bladder Cancer AJCC v8, Stage III Renal Pelvis Cancer AJCC v8, Stage III Ureter Cancer AJCC v8, Stage III Urethral Cancer AJCC v8, Stage IV Bladder Cancer AJCC v8, Stage IV Renal Pelvis Cancer AJCC v8, Stage IV Ureter Cancer AJCC v8, Stage IV Urethral Cancer AJCC v8, Stage IVA Bladder Cancer AJCC v8, Stage IVB Bladder Cancer AJCC v8, Unresectable Bladder Urothelial Carcinoma, Unresectable Renal Pelvis Urothelial Carcinoma, Unresectable Ureter Urothelial Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03513952

Sponsor: National Cancer Institute (NCI)

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Patients must have histologically or cytologically documented locally advanced/inoperable or metastatic urothelial bladder carcinoma (UBC), including renal pelvis, ureters, urinary bladder, and urethra
  • Note: Mixed histology tumors allowed if predominant histology is urothelial carcinoma
  • Note: Small cell or neuroendocrine carcinoma is not allowed if predominant
  • Patients must have recurrent disease after any prior platinum-based chemotherapy regimen
  • Patients must have measurable disease per RECIST 1.1 assessed by computed tomography (CT) scan or magnetic resonance imaging (MRI)
  • ECOG performance status =< 2 (Karnofsky >= 60%)
  • Patients must have a life expectancy of greater or equal to 12 weeks
  • Leukocytes >= 2,500/mcL
  • Absolute neutrophil count >= 1,000/mcL
  • Platelets >= 100,000/mcL
  • Hemoglobin >= 8 g/dL
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (however, patients with known Gilbert's disease who have serum bilirubin level =< 3 x ULN may be enrolled)
  • Aspartate aminotransferase (ALT) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x ULN (AST and/or ALT=< 5 x ULN for patients with liver involvement)
  • Alkaline phosphatase =< 2.5 x ULN (=< 5 +/- ULN for patients with documented liver involvement or bone metastases)
  • Creatinine clearance >= 30 mL/min/1.73 m^2 by Cockcroft-Gault
  • At the discretion of the treating physician, a 24-hour urine creatinine clearance could be obtained and utilized as the gold standard if creatinine clearance by Cockcroft-Gault is < 30, and prevents patient enrollment on the trial
  • International normalized ratio (INR) and activated partial thromboplastin time (aPTT) =< 1.5 x ULN (this applies only to patients who do not receive therapeutic anticoagulation; patients receiving therapeutic anticoagulation, such as low-molecular-weight heparin or warfarin, should be on a stable dose)
  • Patients must provide tissue from an archival tumor sample (obtained within 2 years from screening visit) or newly obtained core, punch, or excisional biopsy of a tumor lesion if deemed relatively safe and technically feasible
  • Female patients of childbearing potential must have a negative urine or serum pregnancy test within 72 hours before receiving the first dose of study agent(s); if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required;
  • Administration of atezolizumab may have an adverse effect on pregnancy and poses a risk to the human fetus, including embryo-lethality; CYT107 has not been tested for reproductive toxicity yet and may expose to the same risk; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) before study entry, for the duration of study participation, and for 5 months (150 days) after the last dose of study agent; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
  • Patients must have the ability to understand and the willingness to sign a written informed consent document
  • Patients positive for human immunodeficiency virus (HIV) are allowed on study, but HIV-positive patients must have:
  • A stable regimen of highly active antiretroviral therapy (HAART)
  • No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections
  • A CD4 count above 250 cells/mcL and an undetectable HIV viral load on standard polymerase chain reaction (PCR)-based tests

Exclusion Criteria:

  • Patients with prior allogeneic bone marrow transplantation or prior solid organ transplantation
  • Patients who have had chemotherapy or radiotherapy within 2 weeks (4 weeks for nitrosoureas or systemic mitomycin C) before the initiation of study treatment
  • Patients who have received more than 2 systemic cytotoxic chemotherapy regimens for metastatic urothelial carcinoma
  • Note: Prior perioperative chemotherapy is allowed and is not counted as a line of therapy if patient relapsed >= 12 months later and received additional platinum-based chemotherapy for metastatic disease
  • Patients who have not recovered from adverse events (other than alopecia) due to agents administered more than 4 weeks earlier (i.e., have residual toxicities > grade 1); however, the following therapies are allowed:
  • Hormone-replacement therapy or oral contraceptives
  • Herbal therapy >= 1 week before initiation of study treatment (herbal therapy intended as anticancer therapy must be discontinued at least 1 week before initiation of study treatment)
  • Palliative radiotherapy for bone metastases > 2 weeks before initiation of study treatment
  • Patients who have received prior treatment with anti-PD-1, or anti-PD-L1 therapeutic antibody, or pathway -targeting agents
  • Patients who have received prior treatment with anti-CTLA-4 may be enrolled, provided the following requirements are met:
  • Minimum of 12 weeks from the first dose of anti-CTLA-4 and > 6 weeks from the last dose
  • No history of severe immune-related adverse effects from anti-CTLA-4 (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] grade 3 and 4)
  • Patients who have received treatment with any other investigational agent within 4 weeks before initiation of study treatment
  • Patients who have received treatment with systemic immunostimulatory agents (including, but not limited to, interferon [IFN]-alpha or interleukin [IL]-2) within 6 weeks before initiation of study treatment
  • Patients who have received treatment with systemic immunosuppressive medications (including, but not limited to, prednisone ( > 10 mg/day or equivalent), cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti TNF] agents) within 2 weeks before initiation of study treatment
  • Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled
  • The use of inhaled corticosteroids, and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed
  • Patients taking bisphosphonate therapy for symptomatic hypercalcemia
  • Note: Use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed
  • Patients with known primary central nervous system (CNS) malignancy or symptomatic CNS metastases are excluded, with the following exceptions:
  • Patients with asymptomatic untreated CNS disease may be enrolled, provided all of the following criteria are met:
  • Evaluable or measurable disease outside the CNS
  • No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm)
  • No history of intracranial hemorrhage or spinal cord hemorrhage
  • No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted
  • No neurosurgical resection or brain biopsy within 28 days before initiation of study treatment
  • Patients with asymptomatic treated CNS metastases may be enrolled, provided all the criteria listed above are met as well as the following:
  • Radiographic demonstration of improvement upon the completion of CNS directed therapy and no evidence of interim progression between the completion of CNS directed therapy and the screening radiographic study
  • No stereotactic radiation or whole-brain radiation within 28 days before initiation of study treatment
  • Screening CNS radiographic study >= 4 weeks from completion of radiotherapy and >= 2 weeks from discontinuation of corticosteroids
  • Note: Patients with CNS metastases enrolled on trial must also have a brain MRI imaging at all standard radiologic evaluation timepoints
  • Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
  • Patients who have a history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  • Patients with known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver/nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH); and inherited liver disease
  • Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBc [antibody to hepatitis B core antigen] antibody test) are eligible
  • Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA)
  • Patients with active underlying autoimmune disease requiring systemic immunosuppressive medication (oral prednisone > 10 mg/day or equivalent). Topical, inhaled, or intra-articular steroids or physiologic endocrine replacement (insulin, levothyroxine, etc.) are permitted. Patients with a history of autoimmune disease that is not currently active require consultation with the protocol principal investigator (PI) and/or Cancer Immunotherapy Trials Network (CITN) Coordinating Center
  • Patients who have a history of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest CT scan; history of radiation pneumonitis in the radiation field (fibrosis) is permitted
  • Patients who have known additional malignancies other than UBC within 2 years before initiation of study treatment; exceptions include malignancies with a negligible risk of metastasis or death and treated with expected curative outcome (e.g., non-melanomatous skin cancers), or localized prostate cancer treated with curative intent and absence of prostate-specific antigen (PSA) relapse or incidental prostate cancer
  • Patients with active tuberculosis (TB)
  • Patients who have leptomeningeal disease
  • Patients who have severe infections within 4 weeks before initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia;
  • Exception: Uncomplicated urinary tract infection will not be considered as a severe infection in these patients
  • Patients who have signs or symptoms of infection within 2 weeks before initiation of study treatment
  • Patients who have received oral or IV antibiotics within 2 weeks before initiation of study treatment; patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible
  • Patients who have major surgical procedure, other than for diagnosis, within 28 days before initiation of study treatment or anticipation of need for a major surgical procedure during the course of the study
  • Patients who have had a live, attenuated vaccine within 4 weeks before initiation of study treatment or anticipation that such a live, attenuated vaccine will be required during the study and up to 5 months after the last dose of atezolizumab.
  • Influenza vaccination should be given during influenza season only (approximately October to March); patients must not receive live, attenuated influenza vaccine within 4 weeks before initiation of study treatment or at any time during the study
  • Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure (New York Heart Association class III or IV), unstable angina pectoris, cardiac arrhythmia, recent myocardial infarction (within the last 6 months), or psychiatric illness/social situations that would limit compliance with study requirements
  • Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or medical (e.g., infectious) illness

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An Open Label, Randomized, Phase III Trial, Evaluating Efficacy of Atezolizumab in Addition to One Year BCG (Bacillus CaLmette-Guerin) Bladder Instillation in BCG-naive Patients With High-risk Non-muscle Invasive Bladder cANcer


Condition: Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03799835

Sponsor: UNICANCER

Phase: Phase 3

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • 1. Signed informed consent form after the last endoscopic surgery (TURBT) 2. Adult man and women ( age ≥18 years) 3. Any high risk non muscle invasive urothelial carcinoma histologically confirmed (mixed histology tumors allowed if urothelial carcinoma histology is predominant) defined on the TURBT as any of the following :
  • T1 tumor and/or
  • High grade (WHO 2004) and/or
  • Grade 3 (WHO1973) and/or
  • Carcinoma in situ (CIS) 4. Tumor tissue available from the surgery for central confirmation of the diagnosis and analysis the expression of PD-L1 5. At least one additional (second) resection of the primary tumor has been performed in any of the following cases [without upstaging towards Muscle Invasive Bladder Cancer (EAU guidelines, 2017)] :
  • T1 tumors at physician's discretion,
  • incomplete initial TURB,
  • no muscle in the specimen (can be omitted if TaLG/G1 tumors or primary CIS only was found) 6. Absence of metastasis in pelvis, abdomen, or chest, as confirmed by a negative baseline computed tomography (CT) or magnetic resonance imaging (MRI) scan no more than 90 days prior to the first study treatment 7. Eastern Cooperative Oncology Group (ECOG) performance status of ≤2 8. Life expectancy ≥12 weeks 9. Systolic blood pressure (BP) <160 mmHg and diastolic BP <95 mmHg, as documented within 7 days prior to the first study treatment (hypertension allowed provided it is controlled) 10. Adequate hematologic and end-organ function, as defined by the following laboratory results obtained within 7 days prior to the first study treatment:
  • absolute neutrophil count (ANC) ≥1500 cells/μL
  • white blood cell (WBC) counts >2500/μL
  • Lymphocyte count ≥300/μL
  • Platelet count ≥100,000/μL
  • Hemoglobin ≥9.0 g/dL
  • aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), and alkaline phosphatase ≤2.5 × the upper limit of normal (ULN)
  • Serum bilirubin ≤1.0 × ULN Patients with known Gilbert disease who have serum bilirubin level ≤3 × ULN may be enrolled.
  • Partial thromboplastin time (PTT)/Prothrombin Time (PT) ≤1.5 × ULN or international normalized ratio (INR) <1.7 × ULN
  • Calculated creatinine clearance ≥20 mL/min (Cockcroft-Gault formula) 11. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of <1% per year during the treatment period and for at least 5 months after the last dose of atezolizumab 12. Patients affiliated to the social security system 13. Patient is willing and able to comply with the protocol for the duration of the trial including undergoing treatment and scheduled visits, and examinations including follow-up.

Exclusion Criteria:

  • 1. Patient having received previous BCG therapy for bladder cancer 2. Any approved anti-cancer therapy, including systemic chemotherapy, or hormonal therapy within 3 weeks prior to initiation of study treatment. Hormone-replacement therapy or oral contraceptives are allowed 3. Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days or five half-lives of the drug, whichever is longer, prior to day 1 of study treatment 4. Malignancies other than urothelial cancer within 5 years prior to Day 1 of cycle 1 of treatment except the following:
  • Patients with localized low risk prostate cancer (defined as Stage ≤T2b, Gleason score ≤7, and PSA at prostate cancer diagnosis ≤20 ng/mL [if measured]) treated with curative intent (radiotherapy and/or prostatectomy) and without prostate-specific antigen (PSA) recurrence are eligible.
  • Patients with low risk prostate cancer (defined as Stage T1/T2a, Gleason score ≤7 and PSA ≤10 ng/mL) who are treatment-naive and undergoing active surveillance are eligible.
  • Patients with malignancies of a negligible risk of metastasis or death (e.g., risk of metastasis or death <5% at 5 years) are eligible provided they meet all of the following criteria: malignancy treated with expected curative intent (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ treated surgically with curative intent) and no evidence of recurrence or metastasis by follow-up imaging and any disease-specific tumor markers. 5. Pregnancy or breastfeeding 6. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins 7. Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation 8. History of autoimmune disease or history of immunosuppression, or conditions associated with congenital or acquired immune deficiency , including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis (see Appendix 6 for a more comprehensive list of autoimmune diseases)
  • Patients with a history of autoimmune-related hypothyroidism/hyperthyroidism on a stable dose of thyroid replacement hormone may be eligible for this study.
  • Patients with controlled Type I diabetes mellitus on a stable dose of insulin regimen may be eligible for this study.
  • History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan may be eligible.
  • History of radiation pneumonitis in the radiation field (fibrosis) is permitted. 9. Serum albumin <2.5 g/dL 10. Known HIV infection 11. Patients with active hepatitis B virus (HBV; chronic or acute; defined as having a positive hepatitis B surface antigen (HBsAg) test prior the randomisation) or hepatitis C.
  • Patients with past HBV infection or resolved HBV infection (defined as the presence of hepatitis B core antibody (HBc Ab) and absence of HBsAg) are eligible. HBV DNA must be obtained in these patients prior to randomisation.
  • Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. 12. Known active tuberculosis 13. Severe infections within 4 weeks prior to Cycle 1, Day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia 14. Signs or symptoms of urinary infection and/or other signs and symptoms > grade 1 (NCI CTCAE v5.0) within 2 weeks prior to Cycle 1, Day 1
  • Patients receiving therapeutic oral or IV antibiotics within 2 weeks prior to Cycle 1, Day 1 are not eligible
  • Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or to prevent chronic obstructive pulmonary disease exacerbation) are eligible. 15. Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within the previous 3 months before Cycle1, Day 1, unstable arrhythmias, or unstable angina.
  • Patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or left ventricular ejection fraction <50% must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate. 16. Major surgical procedure other than for diagnosis within 4 weeks prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure during the course of the study 17. Prior allogeneic stem cell or solid organ transplant 18. Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1 or anticipation if such a live, attenuated vaccine will be required during the study
  • Influenza vaccination should be given during influenza season only (approximately October through May in the Northern Hemisphere and approximately April through September in the Southern Hemisphere). Patients must agree not to receive live, attenuated influenza vaccine (e.g., FluMist®) within 4 weeks prior to Cycle 1, Day 1, at randomization, during treatment or within 5 months following the last dose of atezolizumab (for patients randomized to atezolizumab). 19. Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications 20. Prior treatment with CD137 agonists or immune checkpoint-blockade therapies, including anti-CD40, anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies 21. Treatment with systemic immunostimulatory agents (including but not limited to interferons, interleukin 2 (IL-2)) within 6 weeks or five half-lives of the drug, whichever is shorter, prior to Cycle 1, Day 1 22. Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor (anti-TNF) agents) within 2 weeks prior to Cycle 1, Day 1, or anticipated requirement for systemic immunosuppressive medications during the trial
  • Patients who have received acute, low-dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea, multiple doses for contrast allergy) may be enrolled in the study.
  • The use of inhaled or low-dose (e.g., ≤10 mg/day prednisone) corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, mineralocorticoids (e.g., fludrocortisone for adrenal insufficiency) and low-dose corticosteroids for patients with orthostatic hypotension or adrenocortical insufficiency is allowed. 23. Person deprived of their liberty or under protective custody or guardianship

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Afatinib Dimaleate in Treating Patients With Advanced Refractory Urothelial Cancer


Condition: Distal Urethral Cancer, Proximal Urethral Cancer, Recurrent Bladder Cancer, Recurrent Urethral Cancer, Stage III Bladder Cancer, Stage III Urethral Cancer, Stage IV Bladder Cancer, Stage IV Urethral Cancer, Ureter Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02122172

Sponsor: University of Chicago

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Patients must have locally advanced or metastatic urothelial cancer that is not amenable to surgical treatment
  • Patients must have histologically or cytologically confirmed urothelial tract carcinoma; patients with urothelial carcinoma of the bladder, upper tract, or urethra are eligible
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan for the evaluation of measurable disease (Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST v1.1])
  • Patients must have evidence of disease progression prior to enrollment
  • All patients must have received a prior platinum-based chemotherapy regimen for treatment of urothelial cancer and must now be considered refractory to platinum-based chemotherapy; patients may have received the platinum-containing regimen either in the peri-operative or metastatic setting
  • Patients may have received up to one line of prior systemic chemotherapy for recurrent/metastatic disease; if a platinum-based regimen was received both in the peri-operative setting and again in the metastatic setting, this will be considered 1 line of chemotherapy
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Absolute neutrophil count >= 1,000/mcL
  • Platelets >= 100,000/mcL
  • Hemoglobin >= 8.5g/dL
  • Total bilirubin =< 1.5 institutional upper limit of normal (IULN)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X IULN
  • Calculated creatinine clearance >= 30 mL/min by the modified Cockcroft and Gault Formula OR glomerular filtration rate >= 30 mL/min/body surface area (BSA) by Modification of Diet in Renal Disease or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula
  • Women and men of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Patients must have the ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Patients may not be receiving any other investigational agents
  • Patients with untreated known brain metastases, or treated brain metastases that are clinically unstable
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements
  • Women known to be pregnant
  • Women who are breastfeeding and who are unwilling to stop breastfeeding prior to study entry
  • Patients with known prior human immunodeficiency virus (HIV)-positive status on combination antiretroviral therapy are ineligible; known prior HIV-positive patients with CD4+ =< 500/mm^3 are ineligible (HIV testing is not required as part of this study)
  • Pre-existing interstitial lung disease
  • Inability to take oral medications
  • Prior therapy with afatinib

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A Phase II Study of Nivolumab Combined With Ipilimumab for Patients With Advanced Rare Genitourinary Tumors


Condition: Genitourinary Cancer, Adrenocortical Carcinoma, Non-urothelial Bladder, Non-urothelial Upper Tract, Penile Cancer, Non-adenocarcinoma Prostate Cancer, Refractory Germ-cell, High Grade Neuroendocrine Carcinoma/Small Cell Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03333616

Sponsor: Dana-Farber Cancer Institute

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Age ≥ 18 years at the time of consent.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2 within 28 days prior to registration (Appendix A).
  • Unresectable advanced or metastatic ACC, non-urothelial bladder/upper tract cancer, non-adenocarcinoma prostate cancer, penile cancer, treatment refractory germ-cell tumor or a high grade neuroendocrine carcinoma/small cell carcinoma of any genitourinary site. Pure is defined as >90% and those with a portion of urothelial carcinoma or prostate adenocarcinoma may be included at discretion of the principal investigator. With variant histology in the primary, if metastatic biopsy shows pure variant histology, patient is eligible.
  • at this time only the bladder and neuroendocrine cohorts are open
  • Availability of Formalin-fixed, Paraffin-embedded (FFPE) archival tumor specimens, when available, and willingness of the subject to undergo mandatory fresh tumor biopsy prior to treatment initiation unless determined medically unsafe or not feasible.
  • The archival specimen, when available, must contain adequate viable tumor tissue.
  • The specimen may consist of a tissue block (preferred and should contain the highest grade of tumor) or at least 20 unstained serial sections. Fine-needle aspiration, brushings, cell pellet from pleural effusion, bone marrow aspirate/biopsy are not acceptable.
  • A mandatory biopsy at the time of radiographic progression will be requested from patients who have an initial response to treatment and then subsequently progress as determined by RECIST version 1.1.
  • Measurable disease as defined by RECIST 1.1 within 28 days prior to registration.
  • Demonstrate adequate organ function. All screening labs to be obtained within 28 days prior to first study treatment.
  • Hematological
  • White blood cell (WBC) ≥ 2000 cells/µL
  • Absolute Neutrophil Count (ANC) ≥ 1000 cells/µL
  • Platelet count (plt) ≥ 75,000/ µL
  • Hemoglobin (Hgb) ≥ 9 g/dL
  • Absolute lymphocyte count ≥ 500 cells/µL
  • Renal
  • Serum creatinine OR
  • Calculated creatinine clearance1 ≤ 1.5 x ULN ≥ 40 mL/min
  • Hepatic and Other
  • Bilirubin ≤ 1.5 × upper limit of normal (ULN)
  • AST2 ≤ 2.5 × ULN
  • ALT2 ≤ 2.5 × ULN
  • Alkaline Phosphatase2 ≤ 2.5 × ULN
  • Albumin > 2.5 g/dL
  • Coagulation
  • International Normalized Ratio (INR) or Prothrombin Time (PT)
  • Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 × ULN (unless on prophylactic or therapeutic dosing with low molecular weight heparin or warfarin)
  • Females of childbearing potential must have a negative urine or serum pregnancy test within 28 days prior to registration. NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months
  • Females of childbearing potential and males must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 120 days after treatment discontinuation. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method.
  • As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study

Exclusion Criteria:

  • Prior use of systemic checkpoint inhibitors (including PD-1, PD-L1, and CTLA-4 targeting agents) for the management of ACC, non-urothelial bladder cancer/upper tract, non-adenocarcinoma prostate cancer, penile cancer or treatment refractory germ-cell tumor is excluded
  • Treatment with systemic immunosuppressive medications including but not limited to: prednisone, dexamethasone, cyclosporine, azathioprine, methotrexate, thalidomide, anti-tumor necrosis factor (TNF) agents within 2 weeks of first study dose.
  • Subjects who have received acute, low-dose systemic immunosuppressant medications may be enrolled (such as steroids for acute nausea or cancer-related pain ≤ 10 mg prednisone) maybe enrolled sooner than 2 weeks of first study dose.
  • Subjects with adrenal insufficiency on physiologic replacement doses of steroids may be enrolled (≤ 10 mg prednisone).
  • The use of inhaled, topical, ocular or intra-articular corticosteroids and mineralocorticoids are allowed.
  • Treatment with chemotherapy, hormone therapy, or other investigational therapy within 3 weeks of first study doses. Patients with non-adenocarcinoma of the prostate who may be on luteinizing hormone-releasing hormone agonist/antagonist therapy may continue use. For ACC patients, hormonal agents (e.g mitotane) are allowed for the purpose to control endocrine-related symptoms when needed.
  • Radiotherapy within 14 days of first study treatment with the exception of a single fraction of radiation administered for palliation of symptoms.
  • Known active metastases to the brain, spinal cord or leptomeninges. Patients who are treated with radiotherapy, radiosurgery, or surgery and clinically stable for at least 2 weeks of first study treatment are eligible. Repeat imaging is not required to document treatment response.
  • Malignancies other than ACC, non-urothelial bladder/upper tract cancer, non-adenocarcinoma prostate cancer, penile cancer, treatment refractory germ-cell tumor or genitourinary high grade neuroendocrine carcinoma/small cell carcinoma within 5 years of first study treatment with the exception of those with negligible risk of metastases or death and/or treated with expected curative outcome (included but not limited to carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer for patients with malignancies other than non-adenocarcinoma of the prostate, ductal carcinoma in situ of the breast, non-muscle invasive urothelial carcinoma of the bladder for patients with malignancies other than non-urothelial bladder cancer).
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion protein.
  • Known hypersensitivity to any component of the nivolumab or ipilimumab product.
  • Any active or recent history (within 6 months of first study dose) of autoimmune disease or syndrome that requires systemic corticosteroids (>10 mg daily prednisone equivalent) or immunosuppressive medications including but not limited to: myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with anti-phospholipid syndrome, Wegner's granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. Subjects with vitiligo, controlled type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement therapy are permitted to enroll.
  • Any condition requiring treatment with corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medication within 14 days of the first dose of study drug. Inhaled, topical, ocular or intra-articular corticosteroids and adrenal replacement steroid doses ≤ 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
  • Uncontrolled adrenal insufficiency.
  • History of idiopathic pulmonary fibrosis, organized pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening imaging CT of the chest. History of radiation pneumonitis in the radiation field is permitted.
  • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome.
  • Active or chronic hepatitis B infection (defined as having a positive hepatitis B surface antigen (HBsAg) test at screening). Subject with past or resolved hepatitis B infection (defined as having a negative HBsAg test and positive antibody to hepatitis B core antigen test) are eligible. Hepatitis B viral DNA must be obtained in Subjects with positive hepatitis B core antibody prior to first treatment start.
  • Active hepatitis C infection. Subjects positive hepatitis C antibody test are eligible if PCR is negative for hepatitis C viral DNA.
  • Receipt of therapeutic oral or IV antibiotics within 2 weeks of first study treatment. Subjects receiving routine antibiotic prophylaxis (for dental extractions/procedures) are eligible.
  • Active infection requiring systemic treatment.
  • Significant cardiovascular disease such New York Heart Association (NYHA) class III or greater, myocardial infarction within the previous 3 months, unstable arrhythmias, unstable angina, need for cardiac angioplasty or stenting, coronary artery by-pass graft surgery, symptomatic peripheral vascular disease. Subjects with known coronary artery disease treated with stenting or coronary artery by-pass graft, congestive heart failure not meeting the above criteria, or left ventricular ejection fraction < 50% must be on a stable regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist when appropriate.
  • Prolongation of the QTcF interval defined as > 450 msec for males and > 470 msec for females.
  • Inadequately controlled hypertension (defined as systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 100 mmHg). Anti-hypertensive therapy to achieve these parameters is allowed.
  • History of cerebrovascular accident or transient ischemic attack within 3 months of first study dose.
  • Significant vascular disease (such as aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 3 months of first study dose.
  • Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation) within 4 weeks of first study dose.
  • History of symptomatic deep vein thrombosis or pulmonary embolism within 4 weeks of first study dose.
  • History of abdominal or tracheoesophageal fistula or GI perforation within 6 months of first study treatment.
  • Clinical signs or symptoms of GI obstruction or requirement of routine parenteral nutrition or tube feedings.
  • Evidence of abdominal free air not explained by paracentesis or recent surgical procedure.
  • Serious, non-healing or dehiscing wound or active ulcer.
  • Major surgical procedure within 4 weeks of first study treatment.
  • Presence of any toxicities attributed to prior anti-cancer therapy that are not resolved to grade 2 (CTCAE version 4.0) or baseline that could impose risk for serious complications before administration of study drug,
  • Prior allogenic stem cell or solid organ transplant.

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A Phase 3, Randomized, Study of Neoadjuvant Chemotherapy Alone Versus Neoadjuvant Chemotherapy Plus Nivolumab or Nivolumab and BMS-986205, Followed by Continued Post- Surgery Therapy With Nivolumab or Nivolumab and BMS-986205 in Participants With Muscle- Invasive Bladder Cancer


Condition: Urinary Bladder Neoplasms, Muscle-Invasive Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03661320

Sponsor: Bristol-Myers Squibb

Phase: Phase 3

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Participant must be deemed eligible for Radial Cystectomy (RC) by his/her oncologist and/or urologist, and must agree to undergo Radial Cystectomy (RC) after completion of neoadjuvant therapy.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1

Exclusion Criteria:

  • Clinical evidence of positive lymph node(s) (LN) (≥ 10 mm in short axis) or metastatic bladder cancer
  • Prior systemic therapy, radiation therapy, or surgery for bladder cancer other than trans urethral resection of bladder tumor (TURBT) or biopsies is also not permitted

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Pilot Study of Celecoxib Combined With Gemcitabine and Cisplatin for Neoadjuvant Treatment of Localized, Muscle-Invasive Bladder Cancer


Condition: Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02885974

Sponsor: Baylor College of Medicine

Phase: Phase 1

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Subjects or their legally authorized representative must be informed of the investigational nature of this study, and must sign and give written informed consent in accordance with institutional and federal guidelines.
  • Patients must have histologically proven urothelial carcinoma of the bladder. Those with mixed histology, including a component of urothelial carcinoma, are eligible. Pure small cell carcinoma, pure adenocarcinoma, and pure squamous cell carcinoma are excluded.
  • Patients must have Stage cT2-T4a N0 M0 disease. Clinical T stage is based on the TURBT sample, exam under anesthesia and cross-sectional imaging studies. Patients must undergo cystoscopy and TURBT as part of the staging procedure within 120 days prior to registration. To exclude non-bulky/low-risk tumors, subjects must have documented muscle invasion with at least one of the following: i. Disease measuring at least 10 mm on cross-sectional imaging. Bladder thickening on imaging, by itself, is not adequate. ii. The presence of tumor-associated hydronephrosis.
  • Patients must have staging scans with abdominal/pelvic CT or MRI scan, and CT scan or x-ray of the chest within 56 days prior to registration. If the alkaline phosphatase is > 1.5 x upper limit of normal (ULN), there is a presence of suspicious bone pain, or if there is other clinical suspicion of bone metastases, a whole body bone scan is required within 56 days prior to registration.
  • Patients must have a Zubrod performance status of 0, 1 or 2.
  • Patients must be 18 years of age or older.
  • Patients must have adequate renal function as evidenced by calculated creatinine clearance ≥ 50 mL/min. The serum creatinine value used in the calculation must have been obtained within 28 days prior to registration.
  • Patients must have adequate hepatic function (within 28 days prior to registration), defined as: i. Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (or ≤ 2.5 x ULN with Gilbert's disease); and ii. SGOT (AST) ≤ 2 x institutional ULN; and iii. SGPT (ALT) ≤ 2 x institutional ULN.
  • Patients must have adequate hematologic function (within 28 days prior to registration), defined as: i. Absolute neutrophil count (ANC) ≥ 1,500/μL; and ii. Hemoglobin ≥ 9 g/dL; and iii. Platelets ≥ 100,000/μL.
  • Patients must have tumor tissues from transurethral resection of the bladder tumor (TURBT) that is within 120 days of registration and available for submission. Tissue sample must be sufficient for IHC testing; that is,it must be sufficient tumor tissues for correlative science after pathologic diagnosis [i.e., enough tumor tissue to pass the staging criteria in 4c].
  • Patients must consent to the submission of FFPE blocks and/or unstained slides.

Exclusion Criteria:

  • Patients must not have received previous systemic cytotoxic chemotherapy for urothelial carcinoma.
  • Patients must not have peripheral neuropathy ≥ Grade 2.
  • Patients must not have presence of Class III or IV heart failure, according to New York Heart Association Classifications, or a known left ventricular ejection fraction of less than 50%. Note: LVEF evaluation by echocardiogram or multi-gated acquisition scan (MUGA) is not required prior to registration.
  • Patients must not have a significant history of bleeding events. Patients with a history of a significant bleeding episode (e.g. hemoptysis, upper or lower GI bleeding, grade 3 or 4 gross hematuria unable to be controlled by trans-urethral resection of the bladder tumor) within 6 months of registration are not eligible.
  • No arterial thrombotic events within 6 months of registration, including transient ischemic attack (TIA), cerebrovascular accident (CVA), peripheral arterial thrombus, unstable angina or angina requiring surgical or medical intervention in the past 6 months, or myocardial infarction (MI). Patients with clinically significant peripheral artery disease (i.e., claudication on less than one block) are ineligible. Patients who have experienced a deep venous thrombosis or pulmonary embolus within the past 6 months must be on stable therapeutic anticoagulation to be enrolled to this study.
  • In the opinion of the treating investigator, the patient must be a candidate to receive gemcitabine/cisplatin treatment.
  • Patients must not have aspirin sensitive asthma.
  • Patients must not be known to have hypersensitivity to cisplatin, gemcitabine, or celecoxib.
  • Patients must not have any incidence of or uncontrolled medical illness (e.g. active cardiac symptoms, active systemic infection, etc.) that would limit the patient's ability to participate in the protocol.
  • Patients must not be pregnant or nursing due to the potential teratogenic side effects of the protocol treatment. Women/men of reproductive potential must agree to use an effective contraceptive method during and for 6 months after completing protocol treatment. A negative pregnancy test is required within 7 days prior to registration for women of child-bearing potential.
  • Patients are ineligible if they plan on regular use of NSAIDs at any dose more than 2 times per week (on average) or aspirin at more than 325 mg at least three times per week, on average. Low-dose aspirin not exceeding 100 mg/day is permitted. Patients who agree to stop regular NSAIDs or higher dose aspirin are eligible and no wash out period is required.

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Imaging of Bladder Cancer Using Clinical 3 Tesla MRI and EX-VIVO Ultra-High-Field MRI.


Condition: Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT00938145

Sponsor: Ohio State University Comprehensive Cancer Center

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Known bladder cancer
  • Scheduled for radical cystectomy and lymph node dissection.
  • Able and willing to give valid written informed consent.
  • No contraindications to the MRI(magnetic resonance imaging).

Exclusion Criteria:

  • Not pregnant, planning to become pregnant during the study, or nursing.
  • No allergy to contrast agents.
  • Patient with significant renal insufficiency, i.e. an estimated glomerular filtration rate(eGRF) less than 30 mL/min/1.73m2.
  • Any condition conflict based on the investigation's clinical judgment that would prevent the patient from completion all trial assessments and visits.
  • Inability or unwillingness to cooperate with requirements of this trial.
  • Patients who exhibit noticeable anxiety and/or claustrophobia or who exhibit severe vertigo when they are moved into the MR.
  • Patients with sickle cell anemia and other hemolytic anemia.

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Quantitative Evaluation of a Novel mRNA-based Urine Test for Bladder Cancer in Spinal Cord Individuals With Symptoms or Clinical Findings Suspicious for Bladder Cancer


Condition: Bladder Cancer, Spinal Cord Injury

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT02538809

Sponsor: Swiss Paraplegic Centre Nottwil

Phase:

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Symptoms suspicious of bladder cancer (haematuria, ultrasonic and cystoscopy findings)
  • Chronic spinal cord injury for a minimum of 3 years
  • Informed Consent as documented by signature

Exclusion Criteria:

  • Age < 18 years
  • History of bleeding disorder
  • Bladder augmentation
  • Acute, symptomatic urinary tract infection
  • Pregnancy
  • Urolithiasis
  • Previous intravesical treatment (e.g. bladder irrigation, botulinum toxin injection) < 2 weeks)

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Phase III Randomized Trial of Concurrent Chemoradiotherapy With or Without Atezolizumab in Localized Muscle Invasive Bladder Cancer


Condition: Bladder Urothelial Carcinoma, Muscle Invasive Bladder Carcinoma, Stage II Bladder Cancer AJCC v8, Stage IIIA Bladder Cancer AJCC v8

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03775265

Sponsor: National Cancer Institute (NCI)

Phase: Phase 3

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • STEP 1 REGISTRATION: If this will be the first patient from a registering site to receive a given RT modality (3DCRT vs. IMRT), the site must first submit pre-RT planning documents within 3 days of Step 1 registration and receive approval from Imaging and Radiation Oncology Core (IROC) before randomizing the patient to Step 2. If this will not be the first patient to receive a specific RT modality, the patient should be immediately randomized to Step 2 on the same day.
  • STEP 2 RANDOMIZATION: If patient required review of pre-RT planning, randomization must occur within 14 days of initial registration.
  • Patients must have histologically proven, T2-T4a N0M0 urothelial carcinoma of the bladder within 120 days prior to randomization and no intervening treatment between the histologic proof and randomization. Patients with mixed urothelial carcinoma will be eligible for the trial, but the presence of small cell carcinoma will make a patient ineligible. Patients with lymph nodes >= 1.0 cm in shortest cross-sectional diameter on imaging (computed tomography [CT]/magnetic resonance imaging [MRI] of abdomen and pelvis) must have a biopsy of the enlarged lymph node showing no tumor involvement within 70 days prior to randomization. These patients may be suitable for neoadjuvant chemotherapy and radical cystectomy and are eligible for this trial if they seek out a bladder sparing treatment strategy, however patients who have received prior systemic chemotherapy for bladder cancer are not eligible for the trial.
  • Patients must undergo a transurethral resection of bladder tumor (TURBT) within 70 days prior to randomization. In a situation where a patient is referred from outside to the enrolling institution, patient must have a repeat office cystoscopy by the urologist who will be following the patient on the clinical trial to assess the adequacy of the prior TURBT. This cystoscopy can be performed in urologist office without general anesthesia. Patient may then undergo repeat TURBT if deemed necessary as standard of care by the treating urologist. Patients may have either completely or partially resected tumors as long as the treating urologist attempted maximal resection. Patient must not have T4b disease
  • Patients must undergo radiological staging within 70 days prior to randomization. Imaging of chest, abdomen, and pelvis must be performed using CT or MRI. Patients must not have evidence of T4bN1-3 disease. Eligibility is based on the local radiology report.
  • Patients with hydronephrosis are eligible if they have unilateral hydronephrosis and kidney function meets criteria specified.
  • Patient must be planning to receive one of the protocol specified chemotherapy regimens.
  • All adverse events associated with any prior surgery and intravesical therapy must have resolved to Common Terminology Criteria for Adverse Events (CTCAE) grade =< 2 prior to randomization.
  • Patients must be >= 18 years of age
  • Patient may or may not be radical cystectomy candidates.
  • Absolute neutrophil count (ANC) >=1,500/microliter (mcL) (within 28 days prior to randomization).
  • Platelets >= 100,000/mcL (within 28 days prior to randomization).
  • Hemoglobin >= 9 g/dL (within 28 days prior to randomization).
  • Total bilirubin =< 1.5 x institutional upper limit of normal (IULN) (except patients with Gilbert's syndrome, who must have a total bilirubin < 3.0 mg/dL) (within 28 days prior to randomization).
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5 x IULN (within 28 days prior to randomization).
  • Patients must have adequate renal function as evidenced by calculated creatinine clearance >= 25 mL/min. The creatinine used to calculate the clearance result must have been obtained within 28 days prior to randomization.
  • Patients must have Zubrod performance status =< 2.
  • Patients must have a baseline electrocardiography (ECG) performed within 30 days prior to randomization.
  • If patient has a known history of hepatitis B virus (HBV) or hepatitis C virus (HCV), they must meet the following criteria within 28 days prior to randomization.
  • Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBc [antibody to hepatitis B core antigen] antibody test) are eligible.
  • Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA).
  • Patients who are known to be positive for human immunodeficiency virus (HIV) are eligible only if they have all of the following:
  • A stable regimen of highly active anti-retroviral therapy (HAART)
  • No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections
  • A CD4 count above 250 cells/mcL and an undetectable HIV viral load on standard PCR-based tests within 28 days prior to randomization.
  • Female patients of childbearing potential must have a serum pregnancy test prior to randomization. Patients must not be pregnant or nursing due to the potential teratogenic side effects of the protocol treatment. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of protocol treatment, and for 5 months (150 days) after the last dose of all study drugs. A woman is considered to be of "reproductive potential" if she has had a menses at any time in the preceding 12 consecutive months.
  • Patients must be offered the opportunity to participate in specimen banking for future studies.
  • Patients who can complete Patient-Reported Outcome instruments in English or Spanish must agree to complete the EORTC QLQ-C30, the EORTC QLQ-BLM30, the EPIC Bowel Assessment, and the EQ-5D-5L per protocol schedule of assessment.
  • As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system.

Exclusion Criteria:

  • Patients must not have had urothelial carcinoma or histological variant at any site outside of the urinary bladder within the previous 24 months except Ta/T1/carcinoma in situ (CIS) of the upper urinary tract including renal pelvis and ureter if the patient had undergone complete nephroureterectomy.
  • Patients must not have diffuse CIS based on cystoscopy and biopsy.
  • Patient must not have received any systemic chemotherapy for their bladder cancer.
  • Patient must not have had prior pelvic radiation.
  • Patients must not have received prior treatment for muscle invasive bladder cancer including neoadjuvant chemotherapy for the current tumor.
  • Patients must not have received any systemic therapy (including, but not limited to, interferon alfa-2b, high dose IL-2, pegylated interferon [PEG-IFN], anti-PD-1, anti-PD-L1), for non-muscle invasive bladder cancer. Prior intravesical bacillus Calmette-Guerin (BCG), interferon, and intravesical chemotherapy are allowed.
  • Patients must not have received any of the following prohibited therapies within 28 days prior to randomization or be planning to receive any of the following prohibited therapies during protocol treatment:
  • Anti-cancer systemic chemotherapy or biological therapy not specified in the protocol.
  • Immunotherapy not specified in this protocol.
  • Systemic or intravesical use of any non-study anti-cancer agent (investigational or non-investigational).
  • Investigational agents other than atezolizumab.
  • Live vaccines: Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, shingles, yellow fever, rabies, BCG, and typhoid (oral) vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g. Flu-Mist) are live attenuated vaccines, and are not allowed. Prior administration of intravesical BCG is allowed.
  • Glucocorticoids for any purpose other than to modulate symptoms from an event of suspected immunologic etiology. The use of physiologic doses of corticosteroids (defined as 10 mg prednisone) are acceptable, however site investigators should consult with the study chair for any dose higher than 10 mg prednisone. Dexamethasone 4 mg IV with chemotherapy to prevent nausea is allowed.
  • RANKL infusion: Concurrent denosumab (which binds the cytokine RANKL) for any known indication is prohibited due to interaction with study medication.
  • Patients must not have a major surgical procedure within 28 days prior to randomization. If patient had any surgical procedure then they should have recovered to full presurgical performance status and surgical adverse events should have resolved to grade =< 2. TURBT is not considered a major surgical procedure.
  • Patients must not have received treatment with systemic immunosuppressive medications (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 14 days prior to randomization. Exceptions:
  • Patients may have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea).
  • The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed. Physiological doses equivalent of 10 mg prednisone daily are allowed. Short term steroids given as antiemetic therapy, e.g. 4 mg dexamethasone or equivalent once a week, is allowed.
  • Patients must not have received a live, attenuated vaccine within 4 weeks prior to randomization or anticipate that such a live, attenuated vaccine will be required while on protocol treatment and up to 5 months after the last dose of protocol treatment.
  • Inactivated influenza vaccination should be given during influenza season only (approximately October to March). Patients must not receive live, attenuated influenza vaccine within 4 weeks prior to randomization or while on protocol treatment and up to 5 months after the last dose of protocol treatment.
  • Patients must not have undergone prior allogeneic bone marrow transplantation or prior solid organ transplantation.
  • Patients must not have clinically significant liver disease that precludes patient from treatment regimens prescribed on the study (including, but not limited to, active viral, alcoholic or other autoimmune hepatitis, cirrhosis or inherited liver disease).
  • Patient must not have history of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis.
  • Patients must not have an active infection requiring oral or IV antibiotics within 14 days prior to randomization. Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are not eligible. If patient develops urinary tract infection after TURBT they must have recovered from the infection prior to registration.
  • Patients must not have active autoimmune disease that has required systemic treatment in past two years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Autoimmune diseases include, but are not limited to, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, Graves' disease treated with methimazole or glomerulonephritis.
  • Patient must not have a history of active tuberculosis.
  • No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for two years. Patients with localized prostate cancer who are being followed by an active surveillance program are also eligible.
  • Patients must not be known to be allergic to Chinese hamster egg or ovary cell products and must not have any known major allergic reactions to any study drug.

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Genetic Susceptibility to Bladder Cancer: A Molecular Epidemiology Approach


Condition: Bladder Cancer

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT00848289

Sponsor: M.D. Anderson Cancer Center

Phase:

Eligibility:

  • Age: minimum N/A maximum N/A
  • Gender: All

Inclusion Criteria:

  • Subject has a histologically confirmed diagnosis of superficial or muscle-invasive bladder cancer
  • Subject is a Texas resident.
  • Subject can understand English or a qualified translator is available for the interview.
  • Subjects of any age, gender, or ethnicity are eligible to participate in the study.
  • Subject consents to participate in the study.

Exclusion Criteria:

  • Subject has had prior treatment with systemic chemotherapy or radiotherapy in the past 6 months.
  • Subject has been diagnosed with superficial or muscle-invasive bladder cancer more than twelve months ago.

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QUILT-3.032: A Multicenter Clinical Trial of Intravesical Bacillus Calmette-Guerin (BCG) in Combination With ALT-803 (N-803) in Patients With BCG Unresponsive High Grade Non-Muscle Invasive Bladder Cancer


Condition: Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03022825

Sponsor: ImmunityBio, Inc.

Phase: Phase 2/Phase 3

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Male or female patients 18 years of age or older
  • Histologic confirmation of non-muscle invasive bladder cancer of the transitional cell carcinoma high-grade subtype (mixed histology tumors allowed if transitional cell histology is predominant histology).
  • Histologically confirmed presence of BCG-unresponsive CIS (with or without Ta or T1 disease) or histologically confirmed presence of BCG-unresponsive high-grade Ta or T1 disease.
  • Absence of resectable disease after transurethral resection (TURBT) procedures (residual carcinoma in situ (CIS) acceptable; patients with T1 tumors must undergo repeat resection and biopsy [inclusive of muscularis propria] if initial biopsy did not include muscularis propria). Patients with high-grade Ta and/or T1 disease should have complete resection before study treatment.
  • BCG-unresponsive disease as defined as: (a) Persistent or recurrent CIS (+/- recurrent Ta/T1 disease) within 12 months of receiving adequate BCG (at least five of six doses doses of an initial induction course plus either at least two of three doses of maintenance therapy or at least two of six doses of a second induction course); or (b) Recurrent high-grade Ta/T1 disease within 6 months of completion of adequate BCG (at least five of six doses of an initial induction course plus either at least two of three doses of maintenance therapy or at least two of six doses of a second induction course); or (c) T1 high-grade disease at the first evaluation following an induction BCG course alone (at least five of six doses of an initial induction course).
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
  • Voluntary written informed consent and HIPAA authorization and agree to comply with all protocol-specified procedures and follow-up evaluations

Exclusion Criteria:

  • Recurrence of BCG unresponsive Ta/T1 disease (without presence of CIS) > 6 months after last BCG instillation or BCG unresponsive CIS > 12 months after last BCG instillation.
  • Life expectancy <2 years
  • Any of the following clinical laboratory values at the time of enrollment: (1) Absolute neutrophil count (ANC) <800/µL or (2) Platelets < 50,000/µL
  • Liver function abnormalities as indicated by ongoing hepatic enzyme elevation (AST or ALT) >2 times upper limit of normal (ULN)
  • Renal insufficiency as indicated by a creatinine level >3 times ULN
  • History of or evidence of muscle-invasive, locally advanced, metastatic and/or extravesical bladder cancer (inclusive of the prostatic urethra); or any other cancer within the past 5 years that is progressing or requires active treatment. Exceptions are adequately treated basal cell or squamous cell skin cancer that has undergone potentially curative therapy or in situ cervical cancer; and adequately treated stage I or II cancer or stable prostate cancer from which the patient is currently in complete remission, and is under active surveillance or hormone control.
  • Symptomatic congestive heart failure (CHF), New York Heart Association (NYHA) Class III or IV heart failure or other clinical signs of severe cardiac dysfunction
  • Severe/unstable angina pectoris, or myocardial infarction within 6 months prior to study entry
  • History or evidence of uncontrollable central nervous system (CNS) disease
  • Active systemic infection requiring parenteral antibiotic therapy. All prior infections must have resolved following optimal therapy
  • Concurrent febrile illness, active urinary tract infection, active tuberculosis, a history of hypotension or anaphylactic reactions
  • Ongoing chronic systemic steroid therapy required (>10 mg oral prednisone daily or equivalent)
  • Women who are pregnant or nursing. Female patients of childbearing potential must have a negative pregnancy test and must adhere to using a medically acceptable method of birth control prior to screening and agree to continue its use during the study and for 30 days after the last dose of study drug, or be surgically sterilized (e.g., hysterectomy or tubal ligation). Women of childbearing potential are defined as any female who has experienced menarche and who is NOT permanently sterile or postmenopausal. Postmenopausal is defined as 12 consecutive months with no menses without an alternative medical cause. Males must agree to use barrier methods of birth control while on study and for 90 days post last dose of study drug.
  • Patients currently receiving investigational or commercial anti-cancer agents or anti-cancer therapies other than BCG, ALT-803 and supportive care therapies for active disease.
  • Concurrent use of other investigational agents (not including FDA authorized drugs for the prevention and treatment of COVID-19).
  • Other illness or condition, including laboratory abnormalities, which in the opinion of the Investigator would exclude the patient from participating in this study. This includes, but is not limited to, serious medical conditions or psychiatric illness likely to interfere with participation in the study.

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A Pilot Study of Tazemetostat and Pembrolizumab (MK-3475) in Advanced Urothelial Carcinoma


Condition: Locally Advanced Urothelial Carcinoma, Metastatic Urothelial Carcinoma, Stage III Bladder Cancer AJCC v8, Stage IV Bladder Cancer AJCC v8

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03854474

Sponsor: National Cancer Institute (NCI)

Phase: Phase 1/Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Patients must have pathologically confirmed urothelial carcinoma
  • Note: Patients with mixed histology (with predominant urothelial carcinoma) are eligible
  • Patients must have locally advanced or metastatic disease with either:
  • Arm A: Disease progression during or following (within 12 months) platinum-based chemotherapy (cisplatin or carboplatin).
  • Note: No minimum number of cycles on platinum-based chemotherapy are required. Patients who have had multiple rounds of platinum-based chemotherapy with events of intermittent progressive disease (PD) are eligible as long as progression has been confirmed while on or within 12 months from platinum based therapy OR
  • Arm B: Platinum ineligible status (i.e., patients unable to receive platinum-containing chemotherapy, in the opinion of the treating investigator, regardless of PD-L1 status) or chemotherapy ineligible status (i.e., patients unable to receive treatment with any chemotherapy, in the opinion of the treating investigator, regardless of PD-L1 status)
  • Note: The eligible patient population for Arm B was revised in protocol amendment 10 from 'cisplatin ineligible patients with PD-L1 positive disease' to 'platinum ineligible patients (i.e., unable to receive platinum-containing chemotherapy, in the opinion of the treating investigator, regardless of PD-L1 status) or chemotherapy ineligible patients (i.e., unable to receive treatment with any chemotherapy, in the opinion of the treating investigator, regardless of PD-L1 status).' This revision was made to align with the updated United States (U.S.) Food and Drug Administration (FDA) indications for pembrolizumab (MK-3475) that were released in August of 2021 for patients with locally advanced or metastatic urothelial carcinoma
  • All patients must have measurable disease in accordance with RECIST criteria version (v) 1.1
  • Note: radiological evaluation should occur within 28 days prior to study registration
  • Patients must be naive to prior PD-L1 or EZH2 inhibitors
  • Note: patients in Arm A should have received platinum-based chemotherapy only
  • Age >= 18 years
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Leukocytes >= 3000/mcL (performed within 14 days prior to registration)
  • Absolute neutrophil count (ANC) >= 1500/mcL (performed within 14 days prior to registration)
  • Platelets >= 100 000/mcL (performed within 14 days prior to registration)
  • Hemoglobin >= 9 g/dL or >= 4.9 mmol/L (performed within 14 days prior to registration)
  • Creatinine =< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance (CrCl) >= 30 mL/min for patient with creatinine levels > 1.5 x institutional ULN (performed within 14 days prior to registration)
  • Creatinine clearance (CrCl) should be calculated per institutional standard
  • Glomerular filtration rate (GFR) can also be used in place of creatinine or CrCl
  • Total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for patients with total bilirubin levels > 1.5 x ULN (performed within 14 days prior to registration)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN OR =< 5 x ULN for patients with liver metastases (performed within 14 days prior to registration)
  • International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (performed within 14 days prior to registration)
  • Activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants (performed within 14 days prior to registration)
  • The effects of pembrolizumab (MK-3475) and tazemetostat on the developing human fetus are unknown. For this reason and because PD-1 inhibitors as well as EZH2 inhibitors are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.
  • Female patients of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Female patients of childbearing/reproductive potential must be willing to use an adequate method of contraception, for the course of the study through 6 months after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the patient
  • Male patients of reproductive potential must agree to use an adequate method of contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the patient.
  • Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
  • Participants who have the ability to understand and the willingness to sign an Institutional Review Board (IRB) approved written informed consent document are eligible OR Participants with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver are eligible
  • Human immunodeficiency virus (HIV)-infected patients who do not have a history of Kaposi sarcoma and/or Multicentric Castleman Disease, who are on effective anti-retroviral therapy, and who have undetectable viral load within 6 months are eligible for this trial

Exclusion Criteria:

  • Patients with disease that is suitable for local therapy administered with curative intent are not eligible
  • Patients who have had chemotherapy, targeted small molecule therapy, or radiotherapy within 4 weeks prior to entering the study are not eligible
  • Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1 per Common Terminology Criteria for Adverse Events [CTCAE] v.5 ) are not eligible
  • Note: patients with =< grade 2 neuropathy or =< grade 2 alopecia or =< grade 3 audiometric hearing loss are an exception to this criterion and may qualify for the study
  • Note: if patients received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
  • Patients are not eligible who are currently participating and receiving study therapy or have participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
  • Patients who have received transfusion of blood products (including platelets or red blood cells) or administration of colony stimulating factors (including granulocyte colony-stimulating factor [G-CSF], granulocyte macrophage colony-stimulating factor [GM-CSF], or recombinant erythropoietin) within 4 weeks prior to the first dose of treatment are not eligible
  • Patients with a diagnosis of immunodeficiency or are receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment are not eligible
  • Note: the use of physiologic doses of corticosteroids may be approved after consultation with the study principal investigator (PI)
  • Patients with thrombocytopenia, neutropenia, or anemia of grade 3 (per CTCAE 5.0 criteria) are not eligible
  • Patients with abnormalities known to be associated with MDS (e.g. del 5q, chr 7 abn) and myeloproliferative neoplasms (MPN, e.g. JAK2 V617F) observed in cytogenetic testing and deoxyribonucleic acid (DNA) sequencing are not eligible
  • Patients with an ongoing or untreated hematologic malignancy or myeloproliferative disorder, or a prior history of a hematologic malignancy or myeloproliferative disorder are not eligible. (Examples of excluded malignancies/disorders include but are not limited to myelodysplastic syndrome [MDS], T cell lymphoblastic lymphoma (T-LBL), T cell acute lymphoblastic leukemia (T-ALL), and any other myeloid or lymphoid malignancy)
  • Patients who have received prior PD-L1/PD-1/PD-L2 or EZH2 inhibitor therapy are not eligible
  • Patients who have had a prior monoclonal antibody within 4 weeks prior to study day 1 are not eligible
  • Patients must be disease-free of prior invasive malignancies for > 5 years, with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix. If there is a history of prior malignancy, patients must not be receiving other specific treatment for that cancer
  • Patients with known brain metastases or carcinomatous meningitis are excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
  • Note: patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging using the identical imaging modality for each assessment, either magnetic resonance imaging [MRI] or computed tomography [CT] scan, for at least 4 weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment
  • Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to pembrolizumab (MK-3475) or tazemetostat are not eligible
  • Patients with an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs) are not eligible
  • Note: replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
  • Patients with a history of (non-infectious) pneumonitis that required steroids or current pneumonitis are not eligible
  • Patients with a prolongation of corrected QT interval (Fridericia's correction formula [QTcF]) of > 450 msec are not eligible
  • Patients with major surgery within 3 weeks before the first dose of study drugs
  • Note: minor surgery (e.g. minor biopsy of an extracranial site, central venous catheter placement, shunt revision) has no restriction
  • Patients must not have a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator
  • Patients receiving any medications or substances that are strong or moderate inhibitors or inducers of CYP3A =< 14 days prior to study treatment are not eligible
  • Note: The study team should check a frequently-updated medical reference for a list of drugs to avoid or minimize use of. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
  • Patients who are unable to take oral medication OR have malabsorption syndrome or any other uncontrolled gastrointestinal condition (e.g., nausea, diarrhea, vomiting) that might impair the bioavailability of tazemetostat are not eligible
  • Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, interstitial lung disease or active, non-infectious pneumonitis, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled arterial hypertension, stroke within 6 months prior to starting study treatment, or psychiatric illness/social situations that would limit compliance with study requirements are not eligible
  • Pregnant women are excluded from this study because pembrolizumab (MK-3475) and tazemetostat are agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with pembrolizumab (MK-3475) and tazemetostat, breastfeeding should be discontinued if the mother is treated with pembrolizumab (MK-3475) or tazemetostat
  • Pembrolizumab (MK-3475) may have adverse effects on a fetus in utero. Furthermore, it is not known if pembrolizumab (MK-3475) has transient adverse effects on the composition of sperm.
  • Patients are excluded from this study if pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 6 months after the last dose of trial treatment
  • Patients with a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known hepatitis C virus (defined as HCV ribonucleic acid [RNA] [qualitative] is detected) infection are not eligible
  • Note: no testing for hepatitis B and hepatitis C is required unless mandated by local health authority
  • Patients who have received a live vaccine within 30 days of planned treatment start are not eligible
  • Note: seasonal flu vaccines that do not contain live virus are permitted

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A Phase II Open-Label Study of Sacituzumab Govitecan in Unresectable Locally Advanced/Metastatic Urothelial Cancer


Condition: Metastatic Urothelial Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03547973

Sponsor: Gilead Sciences

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Key Inclusion Criteria:

  • Female or male individuals, ≥ 18 years of age (19 Years old for South Korea).
  • Individuals with histologically confirmed urothelial cancer (UC).
  • Eastern Cooperative Oncology Group (ECOG) Performance status score of 0 or 1.
  • Cohort 1: Have had progression or recurrence of urothelial cancer following receipt of platinum-containing regimen (cisplatin or carboplatin):
  • Received a first-line platinum-containing regimen in the metastatic setting or for inoperable locally advanced disease;
  • Or received neo/adjuvant platinum-containing therapy for localized muscle-invasive urothelial cancer, with recurrence/progression ≤12 months following completion of therapy.
  • Cohort 1: In addition to above criterion, have had progression or recurrence of urothelial cancer following receipt of an Anti-programmed Cell Death Protein 1 (anti-PD-1)/ Anti-programmed Death Ligand 1 (PD-L1) therapy.
  • Cohort 2: Were ineligible for platinum-based therapy for first line metastatic disease and have had progression or recurrence of urothelial cancer after a first-line therapy for metastatic disease with anti-PD-1/PD-L1 therapy. Individual may not have received any platinum for treatment of recurrent, metastatic or advanced disease.
  • Cohort 3: Progression or recurrence of UC following a platinum containing regimen in the metastatic setting, or progression or recurrence of UC within 12 months of completion of platinum-based therapy as neoadjuvant or adjuvant therapy.
  • Cohort 4: Individual has not received any platinum-based chemotherapy in the metastatic or unresectable locally advanced setting. Creatinine clearance of at least 50 mL/min calculated by Cockcroft-Gault formula or another validated tool. For individuals receiving cisplatin at 70 mg/m^2 on Day 1 of every 21-day cycle, a creatinine clearance of least 60 mL/min calculated by Cockcroft -Gault formula or another validated tool is required. Individuals with creatinine clearance between 50 to 59 mL/min are to receive a split dose of cisplatin (35 mg/m^2 Day 1 and Day 8 of every 21-day cycle).
  • Cohorts 4, 5, 6: Archival tumor tissue comprising muscle-invasive or metastatic urothelial carcinoma, or a biopsy of metastatic urothelial carcinoma.
  • Cohort 5: Individuals received at least 4 cycles and no more than 6 cycles of GEM + cisplatin.
  • No evidence of progressive disease following completion of first-line chemotherapy (ie, CR, PR, or SD per RECIST v1.1 guidelines as per investigator).
  • Treatment-free interval of 4 to 10 weeks since the last dose of chemotherapy.
  • Cohort 6: Cis-ineligible and no prior therapy for metastatic disease or for unresectable locally advanced disease. Checkpoint inhibitor therapy naïve or >12 months from completion of adjuvant therapy are permitted.
  • Cohorts 4 and 6: Have measurable disease by CT or MRI as per RECIST 1.1 criteria. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
  • Cohorts 5 and 6: Creatinine clearance ≥ 30 mL/min as calculated by the Cockcroft-Gault formula unless otherwise specified
  • Adequate renal and hepatic function.
  • Adequate hematologic parameters without transfusional support.
  • Individuals must have a 3-month life expectancy.

Key Exclusion Criteria:

  • Females who are pregnant or lactating.
  • Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
  • Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (ie, ≤Grade 1 from AEs due to a previously administered agent).
  • For Cohort 5: Alopecia, sensory neuropathy Grade ≤2 is acceptable, or other Grade < 2 adverse events not constituting a safety risk based on the investigator's judgment are acceptable.
  • Requires concomitant medication interfering with ABCA1 transporter or UGT1A1
  • Has an active second malignancy.
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
  • Has known active Hepatitis B or Hepatitis C.
  • Has other concurrent medical or psychiatric conditions.
  • Cohort 3: Has received anti-PD-1/PD-L1 therapy previously.
  • Cohorts 3 to 5: Has an active autoimmune disease that required systemic treatment in past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
  • Cohorts 3 to 6: Has received a live vaccine within 30 days prior to the first dose of study drug(s), has history or evidence of interstitial lung disease (ILD) or non-infectious pneumonitis.
  • Cohort 4: Refractory to platinum (i.e., relapsed ≤ 12 months after completion of chemotherapy) in the neoadjuvant/adjuvant setting.
  • Cohorts 4, 5, and 6: For individuals who received prior CPI, a treatment-free interval >12 months between the last treatment administration and the date of recurrence is required. Note: Other protocol defined Inclusion/

Exclusion Criteria:

  1. may apply.

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A Phase 3, Randomized, Comparator-controlled Clinical Trial to Study the Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Bacillus Calmette-Guerin (BCG) in Participants With High-risk Non-muscle Invasive Bladder Cancer (HR NMIBC) That is Either Persistent or Recurrent Following BCG Induction or That is Naïve to BCG Treatment (KEYNOTE-676)


Condition: High-risk Non-muscle Invasive Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03711032

Sponsor: Merck Sharp & Dohme LLC

Phase: Phase 3

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Have locally and blinded independent central review (BICR)-confirmed histological diagnosis of high-risk non-muscle invasive (T1, high grade Ta and/or CIS) UC of the bladder
  • Has undergone cystoscopy/ transurethral resection of bladder tumor (TURBT) to remove all resectable disease
  • Has provided tissue for biomarker analysis
  • Has Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
  • Has adequate organ function
  • During the treatment period and for ≥7 days after the last dose of BCG, male participants are EITHER abstinent from heterosexual intercourse as their preferred and usual lifestyle and agree to remain abstinent, OR, must agree to use contraception unless confirmed to be azoospermic
  • Female participants who are not pregnant, not breastfeeding, and either not a woman of child bearing potential (WOCBP); or are a WOCBP who agrees to use a contraception method that is highly effective or remains abstinent from heterosexual intercourse during the treatment period and for ≥7 days after the last dose of BCG or 120 days after the last dose of pembrolizumab, whichever comes last BCG Post-induction Cohort (Cohort A) Only
  • Has been treated with one adequate course of BCG induction therapy for the treatment of HR NMIBC
  • Following adequate BCG induction therapy, must have persistent or recurrent HR NMIBC

Exclusion Criteria:

  • Has a history of or concurrent locally advanced (i.e., T2, T3, T4) or metastatic UC
  • Has concurrent extra-vesical (i.e, urethra, ureter, renal pelvis) non-muscle invasive urothelial carcinoma or a history of extra-vesical non-muscle invasive UC
  • Has received prior therapy with anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor
  • Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks of start of study treatment
  • Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks of start of study treatment
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days of start of study treatment
  • Has a known additional malignancy that is progressing or requires active treatment within the past 3 years
  • Has an active autoimmune disease that has required systemic treatment in past 2 years
  • Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
  • Has one or more of the following contraindications to BCG: prior BCG sepsis or systemic infection, total bladder incontinence, or an adverse experience to a previous BCG instillation that resulted in treatment discontinuation and precludes retreating with BCG
  • Has an active infection or diagnosis requiring systemic antimicrobial therapy
  • Has a known history of human immunodeficiency virus (HIV) infection
  • Has a known history of Hepatitis B or known active Hepatitis C virus infection
  • Has current active tuberculosis
  • Has had an allogenic-tissue/solid organ transplant
  • Has any contraindication(s) to IV contrast or is otherwise unable to have screening imaging with IV contrast performed BCG Post-induction Cohort (Cohort A) Only
  • Has persistent T1 disease following an induction course of BCG BCG Naïve Cohort (Cohort B) Only
  • Has received any prior treatment with BCG for their NMIBC within the past 2 years prior to study entry

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