Bladder Cancer

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An Open-label Multi-cohort Phase 1b/2 Study of Derazantinib and Atezolizumab in Patients With Urothelial Cancer Expressing Activating Molecular FGFR Aberrations


Condition: Urothelial Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04045613

Sponsor: Basilea Pharmaceutica

Phase: Phase 1/Phase 2

Eligibility:

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

Inclusion Criteria:

  • Histologically-confirmed transitional cell carcinoma of the urothelium of the upper or lower urinary tract
  • Recurrent or progressing stage IV disease, or surgically unresectable, recurrent or progressing disease
  • Documented central FGFR genetic alteration (FGFR1, FGFR2, or FGFR3 mutations and rearrangements/ fusions )
  • Measurable disease per RECIST 1.1
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2
  • Adequate bone marrow, liver and renal function

Exclusion Criteria:

  • Receipt of chemotherapy, targeted therapies, immunotherapy, or treatment with an investigational anticancer agent within 2 weeks or at least 5 half-lives of the drug whichever is longer before the first dose of study drug.
  • Concurrent evidence of any clinically significant corneal or retinal disorder
  • Phosphatemia greater than institutional upper limit of normal (ULN) at screening
  • Uncontrolled tumor-related hypercalcemia

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A Pilot Study of Neoadjuvant sEphB4-HSA in Patients With Genitourinary Cancers


Condition: Infiltrating Bladder Urothelial Carcinoma, Recurrent Bladder Carcinoma, Stage I Prostate Cancer, Stage I Renal Cell Cancer, Stage II Bladder Urothelial Carcinoma, Stage II Renal Cell Cancer, Stage IIA Prostate Cancer, Stage IIB Prostate Cancer, Stage III Prostate Cancer, Stage III Renal Cell Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02767921

Sponsor: University of Southern California

Phase: Phase 1

Eligibility:

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

Inclusion Criteria:

  • Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information
  • NOTE: HIPAA authorization may be included in the informed consent or obtained separately
  • Eastern Cooperative Oncology Group (ECOG) performance status of =< 1 within 14 days prior to being registered for protocol therapy
  • Females of childbearing potential and males must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time consent is signed until 4 weeks after treatment discontinuation
  • Females of childbearing potential must have a negative pregnancy test within 7 days prior to being registered for protocol therapy
  • NOTE: Subjects are considered not of child bearing potential if they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal
  • Females must not be breastfeeding
  • Cohort A
  • T2, Transitional cell carcinoma (TCC) muscle invasive bladder cancer, (patients who are cisplatin ineligible, decline neoadjuvant and/or ineligible for neoadjuvant chemotherapy); must have histological proof of T2, muscle-invasive transitional cell carcinoma of the bladder with no evidence of metastatic; patient with any degree of fixation of the pelvic sidewall are not eligible
  • Cohort B
  • Prostate cancer (Gleason 7 or less); must have histological proof of Gleason =< 7 with no evidence of metastatic disease (patient with any degree of extra-prostatic capsule extension are not eligible
  • Cohort C
  • Renal cell carcinoma (> pT1b); must have radiologic suspicion or histological proof of clear cell renal cell carcinoma >= 4 cm with no evidence of metastatic disease; patient with any degree of tumor extension into the renal vein are not eligible; patients must be candidates for contrast-enhanced ultrasound (CEUS) imaging and agree to undergo this additional imaging technique
  • Patients must be willing to undergo a biopsy of the cancerous tissue if one was not taken within the previous year, prior to drug initiation if tumor block is not available; biopsy must be done within 14 days of first planned drug dose
  • Patients must be willing to undergo a radiologic scan (computed tomography [CT] or magnetic resonance imaging [MRI], depending on organ involved) after last drug dose and prior to minimally-invasive surgery
  • Eligible for:
  • Cohort A: Robot-assisted radical cystectomy (RARC) as per the attending urologist
  • Cohort B: Robot-assisted radical Nephrectomy (RARN)/robot-assisted partial nephrectomy (RAPN) as per the attending urologist
  • Cohort C: RAPN as per the attending urologist
  • No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancers for which the patient has been disease-free for at least 5 years
  • No treatment with any investigational agent within 30 days prior to being registered for protocol therapy
  • No prior systemic chemotherapy for transitional cell carcinoma of the bladder (prior intravesical therapy is allowed); any other prior chemotherapy must have been completed > 5 years prior to initiation of therapy
  • Prior radiation therapy is allowed provided that no radiation therapy was administered to the urinary bladder
  • NOTE: No radiation therapy within 28 days prior to being registered for protocol therapy; laboratory values must be obtained within 14 days prior to being registered for protocol therapy
  • Total bilirubin < 2.0 X upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) =< 2.5 X ULN
  • Alanine aminotransferase (ALT) =< 2.5 X ULN
  • Serum Creatinine < 2.5 X ULN
  • Absolute neutrophil count (ANC) > 1.5 X K/mm^3
  • Platelets > 100 K/mm^3
  • International normalized ratio (INR) =< 1.2
  • There are currently no known concomitant medications that must be discontinued prior to administration of registration on study and for the duration of sEphB4-HSA
  • No clinically significant infections as judged by the treating investigator
  • No pleural or pericardial effusion of any grade
  • No uncontrolled angina, congestive heart failure or myocardial infraction (MI) within 6 months prior to registration on study
  • No diagnosed arrhythmias
  • No abnormalities on pre-entry electrocardiogram, obtained within 28 days prior to being registered on study
  • No history of diagnosed congenital bleeding disorders (e.g., von Willebrand's disease)
  • No abnormalities no history of diagnosed acquired bleeding disorders within one year (e.g., acquired anti-factor VIII antibodies) of registration on protocol therapy
  • No abnormalities no history of ongoing or recent (less than or equal to 3 months of registration on protocol therapy) significant gastrointestinal bleeding
  • No ongoing anti-coagulation and/or anti-platelet therapies allowed
  • Patients with diagnosed uncontrolled hypertension (> 150/90 mmHg) are to be excluded
  • Patients with hypertension controlled with medications are allowed
  • No evidence of gross hematuria
  • No evidence of hydronephrosis
  • No evidence of a history of a stroke or myocardial infarction within the last 6 months prior to study enrollment
  • No evidence of a history of wound healing complications prior to study enrollment

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Prospective Study of Adjuvant Radiotherapy in High Risk Bladder Cancer.


Condition: Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03718741

Sponsor: Istituto Clinico Humanitas

Eligibility:

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

Inclusion Criteria:

  • Age >18 years
  • Karnofsky index > 60 % (ECOG < 2)
  • Histologically confirmed muscle-invasive bladder cancer (MIBC) submitted to radical cystectomy.
  • Pathological T-stage > pT3, and/or pathological N-stage > pN1, and/or residual tumor present after surgery (R>1)
  • No distant metastases
  • Written informed consent

Exclusion Criteria:

  • Prior RT in the pelvic region
  • Presence of distant metastases
  • Pregnancy
  • Inability to consent

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Patient-reported Outcomes in Bladder Cancer; a Multicentre Randomized Controlled Trial: The iBLAD Study


Condition: Bladder Cancer, Urothelial Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03584659

Sponsor: Rigshospitalet, Denmark

Eligibility:

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

Inclusion Criteria:

  • Urothelial carcinoma
  • Initiating chemo- or immunotherapy
  • No serious cognitive deficits
  • Read and understand Danish
  • Assigned electronic communication with health services with "E-boks"

Exclusion Criteria:

  • None

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A Randomized Phase 2 Study of Erdafitinib Versus Investigator Choice of Intravesical Chemotherapy in Subjects Who Received Bacillus Calmette-Guérin (BCG) and Recurred With High Risk Non-Muscle-Invasive Bladder Cancer (NMIBC) and FGFR Mutations or Fusions


Condition: Urinary Bladder Neoplasms

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04172675

Sponsor: Janssen Research & Development, LLC

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • Histologically confirmed, recurrent, non-muscle-invasive urothelial carcinoma of the bladder. Variant pathology are allowed
  • Tumor with specified fibroblast growth factor receptor (FGFR) mutations or fusions
  • Bacillus Calmette- Guerin (BCG)-unresponsive after adequate BCG therapy or BCG experienced participants
  • Refuses or is not eligible for cystectomy (Cohort 1 and Cohort 2 only)
  • Eastern Cooperative Oncology Group (ECOG) performance status Grade 0-1
  • Must sign an informed consent form (ICF) (or their legally acceptable representative must sign) indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study
  • A woman of childbearing potential must have a negative pregnancy test (beta-hCG [beta-human chorionic gonadotropin]) (urine or serum) within 7 days before randomization (Cohort 1) or the first dose of study drug (Cohort 2 and Cohort 3)
  • Adequate bone marrow, liver, and renal function as specified in the protocol

Exclusion Criteria:

  • Histologically confirmed, muscle-invasive (T2 or higher stage) urothelial carcinoma of the bladder
  • Histopathology demonstrating any small cell component, pure adenocarcinoma, pure squamous cell carcinoma, or pure squamous CIS of the bladder
  • Prior treatment with an FGFR inhibitor
  • Active malignancies other than the disease being treated under study. The only allowed exceptions are: (a) skin cancer treated within the last 24 months that is considered completely cured (b) adequately treated lobular carcinoma in situ (LCIS) and ductal CIS (c) history of localized breast cancer and receiving antihormonal agents, or history of localized prostate cancer (N0M0) and receiving androgen deprivation therapy
  • Current central serous retinopathy or retinal pigment epithelial detachment of any grade

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A Phase II Study of Ipilimumab, Cabozantinib, and Nivolumab in Rare Genitourinary Cancers (ICONIC)


Condition: Bladder Adenocarcinoma, Bladder Clear Cell Adenocarcinoma, Bladder Mixed Adenocarcinoma, Bladder Neuroendocrine Carcinoma, Bladder Small Cell Neuroendocrine Carcinoma, Bladder Squamous Cell Carcinoma, Bladder Urachal Adenocarcinoma, Chromophobe Renal Cell Carcinoma, Collecting Duct Carcinoma, Infiltrating Bladder Lymphoepithelioma-Like Carcinoma, Infiltrating Bladder Urothelial Carcinoma, Infiltrating Bladder Urothelial Carcinoma With Giant Cells, Infiltrating Bladder Urothelial Carcinoma, Nested Variant, Infiltrating Bladder Urothelial Carcinoma, Plasmacytoid Variant, Infiltrating Bladder Urothelial Carcinoma, Sarcomatoid Variant, Kidney Medullary Carcinoma, Large Cell Neuroendocrine Carcinoma, Metastatic Bladder Carcinoma, Metastatic Bladder Large Cell Neuroendocrine Carcinoma, Metastatic Bladder Small Cell Neuroendocrine Carcinoma, Metastatic Bladder Squamous Cell Carcinoma, Metastatic Infiltrating Bladder Urothelial Carcinoma, Clear Cell Variant, Metastatic Infiltrating Bladder Urothelial Carcinoma, Lipid-Rich Variant, Metastatic Infiltrating Bladder Urothelial Carcinoma, Micropapillary Variant, Metastatic Infiltrating Bladder Urothelial Carcinoma, Plasmacytoid Variant, Metastatic Infiltrating Bladder Urothelial Carcinoma, Sarcomatoid Variant, Metastatic Kidney Medullary Carcinoma, Metastatic Malignant Genitourinary System Neoplasm, Metastatic Penile Carcinoma, Metastatic Prostate Small Cell Neuroendocrine Carcinoma, Metastatic Sarcomatoid Renal Cell Carcinoma, Metastatic Urethral Carcinoma, Papillary Renal Cell Carcinoma, Sarcomatoid Renal Cell Carcinoma, Stage IV Bladder Cancer AJCC v8, Stage IV Penile Cancer AJCC v8, Stage IV Prostate Cancer AJCC v8, Stage IV Renal Cell Cancer AJCC v8, Stage IV Urethral Cancer AJCC v8, Stage IVA Bladder Cancer AJCC v8, Stage IVA Prostate Cancer AJCC v8, Stage IVB Bladder Cancer AJCC v8, Stage IVB Prostate Cancer AJCC v8, Testicular Leydig Cell Tumor, Testicular Sertoli Cell Tumor, Urethral Clear Cell Adenocarcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03866382

Sponsor: National Cancer Institute (NCI)

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • Metastatic disease defined as new or progressive lesions on cross-sectional imaging or bone scan. Patients must have at least:
  • One measurable site of disease as per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1
  • One bone lesion on bone scan (tec99 or sodium fluoride [NaF] positron emission tomography [PET]/computed tomography [CT], CT, or magnetic resonance imaging [MRI]) for the bone-only cohort
  • Histologically confirmed diagnosis of one of the following metastatic cohorts:
  • Small cell/ neuroendocrine carcinoma of the bladder
  • All urothelial carcinomas with any amount of neuroendocrine differentiation (including small cell differentiation) will be included. If the tumor is purely neuroendocrine, metastasis from another site of origin should be clinically excluded.
  • Adenocarcinoma of the bladder, or urachal adenocarcinoma, or bladder/urethra clear cell adenocarcinoma
  • must be pure (per World Health Organization [WHO] definition), (i.e. urothelial carcinoma with glandular differentiation is not considered a pure adenocarcinoma.
  • Squamous cell carcinoma of the bladder
  • must be pure (i.e. urothelial carcinoma with squamous differentiation is not considered a pure squamous cell carcinoma).
  • Plasmacytoid urothelial carcinoma
  • Tumor should show predominantly > or equal ~50% plasmacytoid histology (including all types of discohesive growth, such as tumors with signet-ring and/or rhabdoid features as well).
  • Any penile cancer
  • Sarcomatoid renal cell carcinoma
  • Tumor should be predominantly sarcomatoid ~50% (including rhabdoid differentiation) is also unclassified renal cell carcinomas (RCCs): all (assuming they are high grade with metastasis) malignant angiomyolipomas are allowed.
  • Sarcomatoid urothelial carcinoma
  • Tumor should show predominantly ~ 50% sarcomatoid differentiation.
  • Renal medullary carcinoma
  • Per WHO definition, ideally confirmed with immunostains.
  • Renal collecting duct carcinoma
  • Per WHO definition (medullary involvement, predominant tubular morphology, desmoplastic stromal reaction, high grade cytology, infiltrative growth pattern, and absence of other renal cell carcinoma subtype or urothelial carcinoma).
  • Bone only urothelial carcinoma or other non-prostate GU tumor
  • Urethra carcinoma
  • May be of any histology but if urothelial carcinoma then must be isolated to the urethra and not have metachronous or synchronous urothelial carcinoma of the bladder.
  • Other miscellaneous histologic variants of the urothelial carcinoma, such as, but not limited to: micropapillary (Tumor should show predominantly > or equal 50% micropapillary architecture), giant cell, lipid-rich, clear cell and nested variants (Tumor should predominantly > or equal 50% show these features), large cell neuroendocrine carcinoma, lymphoepithelioma-like carcinoma and mixed patterns will be considered, as well as small cell neuroendocrine prostate cancer (Only treatment-naïve primary small cell of prostate with any amount of small cell component allowed. Post-treatment small cell prostatic carcinomas are not allowed), Malignant testicular Sertoli or Leydig cell tumors, and papillary and chromophobe RCC.
  • Note: Translocation positive renal cell carcinoma patients are eligible. However, AREN1721 should be considered before this trial.
  • Hematoxylin and eosin (H&E) slides from diagnostic tumor tissue for retrospective central pathology review
  • Patients may have received up to 2 systemic anti-cancer treatments or be treatment naive. Patients with small cell carcinoma should have received a platinum-based combination regimen either as neoadjuvant, adjuvant or first-line treatment). Patients in the bone-only cohort may be urothelial carcinoma histology but must receive standard cisplatin-based chemotherapy (if cisplatin-eligible).
  • Patients must be able to swallow oral formulation of the tablets
  • Karnofsky performance status >= 80%
  • Absolute neutrophil count (ANC) >= 1,000/mcL
  • Platelet count >= 75,000/mcL
  • Total bilirubin =< 1.5 x upper limit of normal (ULN). For subjects with known Gilbert's disease or similar syndrome with slow conjugation of bilirubin, total bilirubin =< 3.0 mg/dL
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3.0 x institutional upper limit of normal (ULN) (or =< 5 x ULN for patients with liver metastases or Gilbert's disease)
  • Creatinine =< 1.5 x upper limit of normal (ULN) OR creatinine clearance >= 40 mL/min/1.73 m^2 (calculated using the Chronic Kidney Disease Epidemiology [CKD-EPI] equation or Cockcroft-Gault formula) for patients with creatinine levels above institutional normal
  • Hemoglobin >= 9 g/dL (transfusion of packed red blood cells [PRBCs] allowed)
  • Serum albumin >= 3.2 g/dL
  • Lipase and amylase =< 2.0 x ULN and no radiologic (on baseline anatomical imaging) or clinical evidence of pancreatitis
  • Prior treatment with MET or VEGFR inhibitors is allowed. However, prior cabozantinib will not be allowed. Also, patients that have received both prior MET or VEGF and prior PD-1/PD-L1/CTLA-4 (sequentially or in combination) are also not allowed
  • Prior treatment with any therapy on the PD-1/PD-L1 axis or anti- CTLA-4/CTLA-4 inhibitors is allowed, either in the perioperative or in the metastatic setting. However, patients that have received both prior MET or VEGF and prior PD-1/PD-L1/CTLA-4 (sequentially or in combination) are not allowed
  • Human immunodeficiency virus (HIV)-positive patients are eligible if on stable dose of highly active antiretroviral therapy (HAART), no clinically significant drug-drug interactions are anticipated with the current HAART regimen, CD4 counts are greater than 350 and viral load is undetectable
  • Patients with rheumatoid arthritis and other rheumatologic arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication only and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies etc. are eligible but should be considered for rheumatologic evaluation for the presence of target organ involvement and potential need for systemic treatment
  • Patients with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones or medications (e.g. thyroiditis managed with propylthiouracil [PTU] or methimazole) including physiologic oral corticosteroids are eligible
  • Patients who have evidence of active or acute diverticulitis, intra-abdominal abscess, and gastrointestinal (GI) obstruction, within 12 months are not eligible
  • Women of childbearing potential must have a negative pregnancy test =< 7 days prior to registration
  • Women of childbearing potential include women who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are not postmenopausal. Post menopause is defined as amenorrhea >= 12 consecutive months. Note: women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, ovarian suppression or any other reversible reason
  • Pregnant women may not participate in this study because with cabozantinib, nivolumab, and ipilimumab have 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 cabozantinib, nivolumab, and ipilimumab, breastfeeding should be discontinued if the mother is treated with these agents
  • The patient has received no cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) or biologic agents (e.g., cytokines or antibodies) within 2 weeks before the first dose of study treatment
  • The patient has received no radiation therapy:
  • To the lungs and mediastinum or abdomen within 4 weeks before the first dose of study treatment, or has ongoing complications, or is healing from prior radiation therapy
  • To brain metastasis within 3 weeks for whole-brain radiotherapy (WBXRT), and 2 weeks for stereotactic body radiation therapy (SBRT) before the first dose of study treatment
  • To the abdomen within 4 weeks before the first dose of study treatment, or has ongoing complications, or is healing from prior radiation therapy
  • To any other site(s) within 2 weeks before the first dose of study treatment
  • The patient has received no radionuclide treatment within 6 weeks of the first dose of study treatment
  • The patient has received no prior treatment with a small molecule kinase inhibitor within 14 days or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment
  • The patient has received no prior treatment with hormonal therapy within 14 days or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment. Subjects receiving gonadotropin-releasing hormone (GnRH) agonists and antagonists are allowed to participate
  • The patient has not received any other type of investigational agent within 14 days before the first dose of study treatment
  • The patient must have recovered to baseline or Common Terminology Criteria for Adverse Events (CTCAE) =< grade 1 from toxicity due to all prior therapies except alopecia, neuropathy and other non-clinically significant adverse events (AEs) defined as lab elevation with no associated symptoms or sequelae
  • The patient may not have active brain metastases or epidural disease. Patients with brain metastases previously treated with whole brain radiation or radiosurgery who are asymptomatic and do not require steroid treatment for at least 2 weeks before starting study treatment are eligible. Neurosurgical resection of brain metastases or brain biopsy is permitted if completed at least 3 months before starting study treatment. Baseline brain imaging with contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) scans for subjects with known brain metastases is required to confirm eligibility
  • No concomitant treatment with warfarin. Aspirin (up to 325 mg/day), thrombin or factor Xa inhibitors, low-dose warfarin (=< 1 mg/day), prophylactic and therapeutic low molecular weight heparin (LMWH) are permitted
  • No chronic concomitant treatment with strong CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, and St. John's wort) or strong CYP3A4 inhibitors
  • Because the lists of these agents are constantly changing, it is important to regularly consult medical reference texts such as the Physicians' Desk Reference may also provide this information. 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
  • The patient has not experienced any of the following:
  • Clinically-significant gastrointestinal bleeding within 6 months before the first dose of study treatment
  • Hemoptysis of >= 0.5 teaspoon (2.5 mL) of red blood per day within 1 months before the first dose of study treatment
  • Any other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment
  • The patient has no tumor invading any major blood vessels
  • The patient has no evidence of tumor invading the GI tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib. Patients with rectal tumor masses are not eligible.
  • The patient has no uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
  • Cardiovascular disorders including:
  • Congestive heart failure (CHF): New York Heart Association (NYHA) class III (moderate) or class IV (severe) at the time of screening.
  • Concurrent uncontrolled hypertension defined as sustained blood pressure (BP) > 150 mm Hg systolic, or > 90 mm Hg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment
  • The subject has a corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms within 28 days before randomization. Note: if initial QTcF is found to be > 500 ms, two additional electrocardiograms (EKGs) separated by at least 3 minutes should be performed. If the average of these three consecutive results for QTcF is =< 500 ms, the subject meets eligibility in this regard
  • Any history of congenital long QT syndrome
  • Any of the following within 6 months before registration of study treatment:
  • Unstable angina pectoris
  • Clinically-significant cardiac arrhythmias (patients with atrial fibrillation are eligible)
  • Stroke (including transient ischemic attack [TIA], or other ischemic event)
  • Myocardial infarction
  • Cardiomyopathy
  • No significant gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including:
  • Any of the following that have not resolved within 28 days before the first dose of study treatment:
  • Active peptic ulcer disease
  • Acute diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, or malabsorption syndrome
  • None of the following within 2 years before the first dose of study treatment:
  • Abdominal fistula or genitourinary fistula
  • Gastrointestinal perforation
  • Bowel obstruction or gastric outlet obstruction
  • Intra-abdominal abscess. Note: Complete resolution of an intra-abdominal abscess must be confirmed prior to initiating treatment with cabozantinib even if the abscess occurred more than 2 years before the first dose of study treatment
  • Disorders associated with a high risk of fistula formation including percutaneous endoscopic gastrostomy (PEG) tube placement are not eligible
  • No other clinically significant disorders such as:
  • Severe active infection requiring IV systemic treatment within 14 days before the first dose of study treatment
  • Serious non-healing wound/ulcer/bone fracture within 28 days before the first dose of study treatment
  • History of organ or allogeneic stem cell transplant
  • Concurrent uncompensated hypothyroidism or thyroid dysfunction within 7 days before the first dose of study treatment (for asymptomatic patients with an elevated thyroid-stimulating hormone [TSH], thyroid replacement may be initiated if clinically indicated without delaying the start of study treatment)
  • No history of major surgery as follows:
  • Major surgery within 3 months of the first dose of ca

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Prospective Randomized Phase II Trial: Comparing the Prognostic Value of Routine Lymphadenectomy Versus Lymphadenectomy Only for Lymph Nodes Enlargement Found in Preoperative Imaging or During Surgery Undergoing Nephroureterectomy in Patients With Primary Upper Tract Urothelial Carcinoma


Condition: Lymph Node Dissection

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03474926

Sponsor: RenJi Hospital

Phase: Phase 2

Eligibility:

  • Age: minimum 15 Years maximum 80 Years
  • Gender: All

Inclusion Criteria:

  • clinically diagnosed with upper tract urothelial carcinoma
  • have no distant metastasis
  • have an Eastern Cooperative Oncology Group (ECOG) score 0 to 2
  • expected to receive radical nephroureterectomy

Exclusion Criteria:

  • a prior history of bladder cancer
  • administration of neoadjuvant chemotherapy
  • deny to receive long term follow-up
  • patients with contralateral UTUCs
  • patients with synchronous muscle invasive bladder cancer

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Phase II Study of Maintenance Anti-PD-L1 Treatment With Atezolizumab After Chemo-radiotherapy for Muscle-infiltrating Bladder Cancer Patients Not Eligible for Radical Cystectomy: Bladder Sparing


Condition: Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03697850

Sponsor: UNICANCER

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum 100 Years
  • Gender: All

Inclusion Criteria:

  1. Muscle-invasive bladder cancer (MIBC) pT2-T3 histologically confirmed: Urothelial and squamous cell histological types are allowed. De novo MIBC or after a history of non-muscle-invasive bladder cancer.
  2. Complete transurethral resection of bladder tumour (TURBT), either: within 6 weeks of selection if no chemotherapy was administered, or before starting chemotherapy.
  3. Patients for which chemo-radiotherapy is planned
  4. No major pelvic involvement: pelvic nodes ≤15 mm on CT scan.
  5. No distant metastasis.
  6. Patient unfit for radical cystectomy because of age, comorbidities, or patient's refusal.
  7. Patients ≥18 years old
  8. Eastern Cooperative Oncology Group (ECOG) performance status ≤
  9. Life expectancy ≥12 months.
  10. Haematological and biological parameters: White blood cell count ≥4000/mm³ Platelet count ≥100000 cells/mm³ Haemoglobin level ≥9 g/dL or corrected after transfusion Adequate renal function: clearance >50 mL/min (Cockcroft). Adequate hepatic function: Aspartate aminotransferase (AST [SGOT]) and Alanine aminotransferase (ALT [SGPT]) ≤2.5 x upper limit of normal (ULN), or ≤3.5 x ULN in the case of concurrent disease with known etiology and for which a corrective treatment is possible.
  11. Patients of childbearing potential who agree to use a medically acceptable method of contraception during the study and for 120 days after the last study treatment. Women must have a negative urine or serum pregnancy test before receiving the study treatment and within 14 days prior to selection.
  12. Patients having provided written informed consent prior to any study-related procedures.
  13. Patients affiliated to the social security scheme.
  14. Patients willing and able to comply with the scheduled visits, treatment plan, laboratory tests, and other study procedures indicated in the protocol.
  15. Patient consents to the use of their collected tumour specimen, as well as, blood samples as detailed in the protocol for future scientific research which includes but not limited to DNA, RNA, and protein-based biomarker detection. Exclusion Criteria:
  16. Prior pelvic irradiation.
  17. MIBC histology other than urothelial or squamous cell carcinomas (e.g., adenocarcinomas, micropapillary, sarcomas, or small cell histological types).
  18. History of neoplastic disease, during the 3 years before selection, except completely resected cutaneous basal-cell carcinomas, carcinoma in-situ or localised prostate cancer without biochemical recurrence following definitive treatment.
  19. Prior treatment with CD137 agonists or immune checkpoint inhibitors, including anti-cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4), anti-programmed death-1 receptor (anti-PD-1), and anti-programmed death-ligand 1 (anti-PD-L1) therapeutic antibodies.
  20. Contraindications for pelvic radiotherapy (e.g., inflammatory bowel disease).
  21. History of immunodeficiency, including HIV infection, or systemic steroid therapy for any other disease.
  22. A history of active autoimmune disease, except autoimmune-related hypothyroidism and type I diabetes mellitus (see appendix 5).
  23. History of severe allergic anaphylactic reactions to chimeric, human or humanised antibodies, or fusion proteins.
  24. Known hypersensitivity to Chinese hamster ovary (CHO) cell products or any component of the atezolizumab formulation.
  25. Prior allogeneic stem cell or solid organ transplant.
  26. Patients with the following severe acute co-morbidity are not eligible: Unstable angina or congestive heart failure that required hospitalisation in the 6 months before selection. Transmural myocardial infarction in the 6 months prior to selection. Acute bacterial or fungal infection requiring intravenous antibiotics at selection. Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalisation or precluding study therapy at the time of selection. Severe hepatic disease: Child-Pugh Class B or C.
  27. Patients with any other disease or illness which requires hospitalisation or is incompatible with the study treatment are not eligible.
  28. Patients unable to comply with study obligations for geographic, social, or physical reasons, or who are unable to understand the purpose and procedures of the study.
  29. Patients enrolled in another therapeutic study within 30 days of selection.
  30. Pregnant or breast feeding women.
  31. Person deprived of their liberty or under protective custody or guardianship. Inclusion phase Inclusion Criteria:
  32. Patients who have received standard (chemo)-radiotherapy ≥60 gray (Gy) or equivalent on the bladder according to the local practice.
  33. The first administration of atezolizumab must be performed 30 (+/-5) days after the last session of radiotherapy (RT).
  34. ECOG performance status ≤
  35. Haematological and biological parameters: White blood cell count ≥3000/mm³ Platelet count ≥100000 cells/mm³ Haemoglobin level ≥9 g/dL or corrected after transfusion Adequate renal function: clearance >50 mL/min (Cockcroft) Adequate hepatic function: AST (SGOT) and ALT (SGPT) ≤2.5 x ULN, or ≤3.5 x ULN in the case of concurrent disease with known etiology and for which a corrective treatment is possible.
  36. Patients of childbearing potential who agree to use a medically acceptable method of contraception during the study and for 120 days after the last study treatment. Women must have a negative urine or serum pregnancy test before receiving the study treatment and within 14 days prior to inclusion.
  37. Patients having provided written informed consent prior to any study-related procedures.
  38. Patients willing and able to comply with the scheduled visits, treatment plan, laboratory tests, and other study procedures indicated in the protocol.
  39. Patient consents to the use of their collected tumour specimen, as well as, blood samples as detailed in the protocol for future scientific research which includes but not limited to DNA, RNA, and protein-based biomarker detection.

Exclusion Criteria:

  1. Prior pelvic irradiation.
  2. MIBC histology other than urothelial or squamous cell carcinomas (e.g., adenocarcinomas, micropapillary, sarcomas, or small cell histological types).
  3. History of neoplastic disease, during the 3 years before selection, except completely resected cutaneous basal-cell carcinomas, carcinoma in-situ or localised prostate cancer without biochemical recurrence following definitive treatment.
  4. Prior treatment with CD137 agonists or immune checkpoint inhibitors, including anti-cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4), anti-programmed death-1 receptor (anti-PD-1), and anti-programmed death-ligand 1 (anti-PD-L1) therapeutic antibodies.
  5. Contraindications for pelvic radiotherapy (e.g., inflammatory bowel disease).
  6. History of immunodeficiency, including HIV infection, or systemic steroid therapy for any other disease.
  7. A history of active autoimmune disease, except autoimmune-related hypothyroidism and type I diabetes mellitus (see appendix 5).
  8. History of severe allergic anaphylactic reactions to chimeric, human or humanised antibodies, or fusion proteins.
  9. Known hypersensitivity to Chinese hamster ovary (CHO) cell products or any component of the atezolizumab formulation.
  10. Prior allogeneic stem cell or solid organ transplant.
  11. Patients with the following severe acute co-morbidity are not eligible: Unstable angina or congestive heart failure that required hospitalisation in the 6 months before selection. Transmural myocardial infarction in the 6 months prior to selection. Acute bacterial or fungal infection requiring intravenous antibiotics at selection. Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalisation or precluding study therapy at the time of selection. Severe hepatic disease: Child-Pugh Class B or C.
  12. Patients with any other disease or illness which requires hospitalisation or is incompatible with the study treatment are not eligible.
  13. Patients unable to comply with study obligations for geographic, social, or physical reasons, or who are unable to understand the purpose and procedures of the study.
  14. Patients enrolled in another therapeutic study within 30 days of selection.
  15. Pregnant or breast feeding women.
  16. Person deprived of their liberty or under protective custody or guardianship. Inclusion phase Inclusion Criteria:
  17. Patients who have received standard (chemo)-radiotherapy ≥60 gray (Gy) or equivalent on the bladder according to the local practice.
  18. The first administration of atezolizumab must be performed 30 (+/-5) days after the last session of radiotherapy (RT).
  19. ECOG performance status ≤
  20. Haematological and biological parameters: White blood cell count ≥3000/mm³ Platelet count ≥100000 cells/mm³ Haemoglobin level ≥9 g/dL or corrected after transfusion Adequate renal function: clearance >50 mL/min (Cockcroft) Adequate hepatic function: AST (SGOT) and ALT (SGPT) ≤2.5 x ULN, or ≤3.5 x ULN in the case of concurrent disease with known etiology and for which a corrective treatment is possible.
  21. Patients of childbearing potential who agree to use a medically acceptable method of contraception during the study and for 120 days after the last study treatment. Women must have a negative urine or serum pregnancy test before receiving the study treatment and within 14 days prior to inclusion.
  22. Patients having provided written informed consent prior to any study-related procedures.
  23. Patients willing and able to comply with the scheduled visits, treatment plan, laboratory tests, and other study procedures indicated in the protocol.
  24. Patient consents to the use of their collected tumour specimen, as well as, blood samples as detailed in the protocol for future scientific research which includes but not limited to DNA, RNA, and protein-based biomarker detection. Exclusion Criteria: The same non-inclusion criteria of the selection phase have to be respected.

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Prospective Cohort-study for Evaluation of Clinical Outcome of Robot-assisted Cystectomy With Intracorporeal Reconstruction of Urinary Diversion


Condition: Urothelial Carcinoma, Cystectomy, Urinary Diversion, Complication of Surgical Procedure, Complication, Postoperative, Neobladder, Ileal Conduit, Robotic Surgical Procedures

Study Type: Observational [Patient Registry]

Clinical Trials Identifier NCT 8-digits: NCT03280459

Sponsor: Kantonsspital Winterthur KSW

Phase:

Eligibility:

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

Inclusion Criteria:

  • age 18 years
  • informed consent for operation and data use
  • Oncologic patients that qualify for radical cystectomy according to institutional tumor-board decision or patients with functional indications after failure of all other therapy modalities and receive a cystectomy

Exclusion Criteria:

  • age <18 years
  • declined informed consent / data use
  • pregnancy

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Phase II Randomized Placebo-Controlled Clinical Trial of Genistein in Reducing the Toxicity and Improving the Efficacy of Intravesical Therapy


Condition: Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT01489813

Sponsor: Emory University

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  1. Male or female gender
  2. 18 years or older
  3. Diagnosis of superficial bladder cancer
  4. Scheduled for induction BCG intravesical therapy
  5. Willing and able to give blood sample
  6. Willing and able to fill out a pill diary to ensure compliance
  7. Willing and able to sign informed consent
  8. Birth control is not required for this study!

Exclusion Criteria:

  1. Patients who are pregnant
  2. Diagnosis of muscle-invasive bladder cancer
  3. Unwillingness to follow study protocol and compliance procedures
  4. HIV positive or immunocompromised
  5. Receiving concurrent immunotherapy or chemotherapy
  6. Presence of concurrent second cancer (active, not history)

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A Phase 1b-2 Study to Evaluate Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of Various Regimens of Erdafitinib in Subjects With Metastatic or Locally Advanced Urothelial Cancer


Condition: Urothelial Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03473743

Sponsor: Janssen Research & Development, LLC

Phase: Phase 1/Phase 2

Eligibility:

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

Inclusion Criteria:

  • Histologic demonstration of transitional cell carcinoma of the urothelium. Variant urothelial carcinoma histologies such as glandular or squamous differentiation, or evolution to more aggressive phenotypes such as sarcomatoid or micropapillary change are acceptable
  • Metastatic or locally advanced urothelial cancer
  • Must have measurable disease by radiological imaging according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) at baseline
  • Prior systemic therapy for metastatic urothelial cancer: (a) For Phase 1b erdafitinib + cetrelimab cohort: Any number of lines of prior therapy; (b) For Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort: No prior systemic therapy for metastatic disease; and renal function for participants must have a creatinine clearance (CrCl) greater than (>) 30 milliliter per minute (mL/min) to receive carboplatin and >60 mL/min to receive cisplatin as calculated by Cockcroft Gault and (c) Phase 2: No prior systemic therapy for metastatic disease and cisplatin-ineligible based on: ECOG PS 0-1 and at least one of the following criteria: Renal function defined as creatinine clearance (CrCl) less than (˂) 60 mL/min as calculated by Cockcroft-Gault; Grade 2 or higher peripheral neuropathy per NCI-CTCAE version 5.0; Grade 2 or higher hearing loss per NCI-CTCAE version 5.0 OR ECOG PS 2
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) grade of: (a) Phase 1b erdafitinib + cetrelimab cohort: ECOG 0-2; (b) Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort: ECOG 0-1 for cisplatin and 0-2 for carboplatin (c) Phase 2: ECOG 0-2

Exclusion Criteria:

  • Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 30 days prior to Cycle 1 Day 1. For Phase 1b, participants who have received the following prior antitumor therapy: received nitrosoureas and mitomycin C within 6 weeks
  • Phase 1b erdafitinib + cetrelimab cohort: Chemotherapy within 3 weeks of Cycle 1 Day 1; Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort and Phase 2: Prior neoadjuvant/adjuvant chemotherapy is allowed if the last dose was given >12 months prior to recurrent disease progression and did not result in drug-related toxicity leading to treatment discontinuation
  • Prior anti-programmed death receptor-1 (PD-1), anti-programmed death ligand-1 (PD-L1), or anti-programmed death ligand-2 (PD-L2) therapy. Prior neoadjuvant/adjuvant checkpoint inhibitor therapy is allowed if the last dose was given more than (>)12 months prior to recurrent disease progression and did not result in drug-related toxicity leading to treatment discontinuation. PD-1 for non-muscle invasive bladder cancer is also allowed
  • Active malignancies requiring concurrent therapy other than urothelial cancer
  • Symptomatic central nervous system metastases

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An Open-label, Single-arm, Single-center, Phase II Study to Evaluate the Efficacy and Safety of Recombinant Humanized Anti-HER2 Monoclonal Antibody-MMAE Conjugate for Injection in Subjects With HER2-negative Metastatic or Unresectable Urothelial Cancer


Condition: Urothelial Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04073602

Sponsor: RemeGen

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum 80 Years
  • Gender: All

Inclusion Criteria:

  • Voluntary agreement to provide written informed consent.
  • Male or female, Age ≥ 18 years.
  • Predicted survival ≥ 12 weeks.
  • Diagnosed with histologically or cytologically-confirmed locally advanced or metastatic urothelial cancer, originate from bladder, renal pelvis, ureter and urinary tract.
  • Unresectable or disease progression (i.e. locally advanced/metastasis) after surgery and at least regular chemotherapy including gemcitabine, cisplatin AND paclitaxel. Disease progression within 6 months of the completion of neo-adjuvant and adjuvant chemotherapy with gemcitabine, cisplatin AND paclitaxel is also eligible.
  • Measurable lesion according to RECIST 1.1.
  • HER2 negative (i.e. IHC -or 1+) as confirmed by the department of Pathology in Beijing Cancer Hospital. Subject is able to provide specimens from primary or metastatic lesions for HER2 tests.
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
  • Adequate organ function, evidenced by the following laboratory results within 7 days prior to the study treatment: Cardiac ejection fraction ≥ 50 %. Hemoglobin ≥ 9g/dL; Absolute neutrophil count ≥ 1.5×10^9/L Platelets ≥ 100×10^9/L; Total bilirubin ≤ 1.5× ULN; AST and ALT ≤ 2.5×ULN and ≤ 5 x ULN with hepatic metastasis; Serum creatinine ≤1.5×ULN.
  • All female subjects will be considered to be of child-bearing potential unless they are postmenopausal, or have been sterilized surgically.Female subjects of child-bearing potential must agree to use two forms of highly effective contraception. Male subjects and their female partner who are of child-bearing potential must agree to use two forms of highly effective contraception.
  • Willing to adhere to the study visit schedule and the prohibitions and restrictions specified in this protocol.

Exclusion Criteria:

  • Known hypersensitivity to the components of Recombinant Humanized Anti-HER2 Monoclonal Antibody-MMAE Conjugate.
  • Toxicity of previous anti-tumor treatment not recovered to CTCAE Grade 0-1 (with exception of Grade 2 alopecia).
  • Pleural or abdominal effusion with clinical symptoms that requires ongoing treatment.
  • History of receiving any anti-cancer drug/biologic treatment within 3 weeks prior to trial treatment.
  • History of major surgery within 4 weeks of planned start of trial treatment.
  • Has received a live virus vaccine within 4 weeks of planned start of trial treatment.
  • Currently known active infection with HIV or tuberculosis.
  • Diagnosed with HBsAg , HBcAb positive and HBV DNA copy positive, or HCVAb positive.
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  • History of other malignancy within the previous 3 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or cancers with a similar curative outcome as those mentioned above.
  • known central nervous system metastases.
  • Uncontrolled hypertension, diabetes, Interstitial lung Disease, or COPD;
  • Treated with systemic treatment (e.g. immunomodulators, corticosteroids or immunosuppressants) for the autoimmune disease within 2 years prior to the study treatment.
  • NYHA Class III heart failure
  • Pregnancy or lactation.
  • Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.

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A Phase 1, Open-Label, Dose Escalation Study of PRS-343 in Patients With HER2-Positive Advanced or Metastatic Solid Tumors


Condition: HER2-positive Breast Cancer, HER2-positive Gastric Cancer, HER2-positive Bladder Cancer, HER2-positive Solid Tumor

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03330561

Sponsor: Pieris Pharmaceuticals, Inc.

Phase: Phase 1

Eligibility:

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

Inclusion Criteria:

  1. Signed written informed consent obtained prior to performing any study procedure, including pre-screening and screening procedures.
  2. Men and women ≥18 years.
  3. Dose escalation: Histologically or cytologically confirmed diagnosis of unresectable/locally advanced and/or metastatic HER2+ solid tumor malignancy and for which standard therapies are not available, are no longer effective, are not tolerated, or have been declined by the patient. Expansion cohort: Locally advanced or metastatic HER2+ solid tumors considered likely to respond to a HER2-targeted CD137 agonist (e.g. gastric/gastroesophageal/esophageal, breast, bladder).
  4. Dose escalation and expansion cohort: HER2+ tumors documented by clinical pathology report:
  5. Assessment of HER2 status in patients with breast cancer should follow the 2013 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) criteria (37) as practicable.
  6. Assessment of HER2 status in patients with gastric and gastroesophageal junction adenocarcinoma should follow the criteria published by Ruschoff et al. (38) as practicable.
  7. Assessment of HER2 status in patients with non-breast/non-gastric cancers may follow local institutional criteria. These criteria should be made available to the Sponsor.
  8. All patients with breast and gastric/gastroesophageal junction cancers should have HER2 testing performed using a FDA approved test in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory.
  9. Patients for whom the clinical pathology report includes only IHC as 3+ (does not reflex to ISH) may enroll without written report of ISH determined HER2 copy number, provided the investigational site confirms that archival tissue is available.
  10. Patients with breast cancer and gastric and gastroesophageal junction cancer must have received at least 1 prior HER2 targeted therapy for advanced/metastatic disease.
  11. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-
  12. Estimated life expectancy of at least 3 months.
  13. Measurable disease according to RECIST v1.
  14. Adequate organ function as defined below:
  15. Serum AST and ALT ≤ 3 X ULN
  16. Total serum bilirubin ≤ 1.5 X ULN
  17. Serum creatinine ≤ 1.5 X ULN OR calculated glomerular filtration rate (GFR) by Cockcroft-Gault formula ≥ 50 mL/min
  18. Hemoglobin ≥ 9 g/dL
  19. ANC ≥ 1500/mm3
  20. Platelet count ≥ 75,000/mm3
  21. Left ventricular ejection fraction (LVEF) determined by echocardiogram or multi-gated acquisition scan ≥ 50%
  22. Any prior cumulative doxorubicin dose must be ≤ 360 mg/m2; prior cumulative epirubicin dose must be ≤ 720 mg/m
  23. Women of childbearing potential must have a negative serum or urine pregnancy test within 96 hours prior to start of study drug.
  24. Women must not be breastfeeding.
  25. Women of childbearing potential must agree to follow instruction for method(s) of contraception for the duration of treatment with study drug PRS-343 plus 90 days post-treatment completion.
  26. Males who are sexually active with women of childbearing potential must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug PRS 343 plus 90 days post-treatment completion.

Exclusion Criteria:

  1. Known uncontrolled central nervous system (CNS) metastases and/or carcinomatous meningitis. Note: Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of study treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are clinically stable off steroids for at least 7 days prior to study treatment. Carcinomatous meningitis precludes a patient from study participation regardless of clinical stability.
  2. History of acute coronary syndromes, including myocardial infarction, coronary artery bypass graft, unstable angina, coronary angioplasty or stenting within past 24 weeks.
  3. History of or current Class II, III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system (Appendix B).
  4. History of ejection fraction drop below the lower limit of normal with trastuzumab and/or pertuzumab.
  5. Medical, psychiatric, cognitive or other conditions that compromise the patient's ability to understand the patient information, to give informed consent, to comply with the study protocol or to complete the study.
  6. Any severe concurrent disease or condition (includes active infections, cardiac arrhythmia, interstitial lung disease) that in the judgment of the investigator would make study participation inappropriate for the patient.
  7. Previously known infection with human immunodeficiency virus (HIV); or hepatitis B or hepatitis C infection. Patients with positive hepatitis B core antibody (HBcAb) require assessment and monitoring of virus deoxyribonucleic acid (DNA) status; patients with positive hepatitis C virus (HCV) core antibody can enroll if HCV ribonucleic acid (RNA) is negative. Patients with latent or active hepatitis B infection are excluded from the pre-treatment Cohort receiving obinutuzumab.
  8. History of infusion reactions to any component/excipient of PRS-3
  9. Systemic steroid therapy (>10 mg daily prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment (Note: topical, inhaled, nasal and ophthalmic steroids are not prohibited). This criterion does not apply to patients receiving obinutuzumab as pre-treatment.
  10. Autoimmune disease that has required systemic treatment in the past (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 allowed.
  11. Has not recovered from the adverse effect of previous anticancer treatments to pre-treatment baseline or Grade 1 except for alopecia, anemia (hemoglobin must meet the study inclusion criteria) and peripheral neuropathy (which must have recovered to ≤ Grade 2) nausea and diarrhea if anti-emetic and anti-diarrheal treatment has not been exhausted.
  12. History of a second primary cancer with the exception of 1) curatively treated non-melanomatous skin cancer, 2) curatively treated cervical or breast carcinoma in situ, or 3) other malignancy with no known active disease present and no treatment administered during the last 2 years.
  13. Receipt of investigational treatment within 3 weeks of scheduled Cycle 1 Day 1 (C1D1) dosing.
  14. Receipt of cytotoxic chemotherapy within 3 weeks (6 weeks for nitrosoureas and mitomycin C) of scheduled C1D1 dosing.
  15. Receipt of radiation therapy within 3 weeks of scheduled C1D1 dosing, unless the radiation comprised a limited field to non-visceral structures (e.g., limb bone metastasis).
  16. Receipt of treatment with immunotherapy, biological therapies, targeted small molecules, hormonal therapies within 3 weeks of scheduled C1D1 dosing.
  17. Receipt of trastuzumab or ado-trastuzumab emtansine or any other experimental drug that engages the same epitope as trastuzumab within 4 weeks of scheduled C1D1 dosing.
  18. Concurrent enrollment in another therapeutic clinical trial.
  19. Major surgery within 3 weeks of scheduled C1D1 dosing.

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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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The DUTRENEO Trial: A Prospective Study to Individualize the Approach With DUrvalumab (MEDI4736) and TREmelimumab in NEOadjuvant Bladder Cancer Patients.


Condition: Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03472274

Sponsor: Fundacion CRIS de Investigación para Vencer el Cáncer

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • 1. Male and female subjects; age ≥ 18 years at the time of study entry. 2. Subjects must provide written informed consent prior to performance of any protocol-related procedures, including screening evaluations and must be willing to comply with treatment and follow up. 3. Subjects must have histologic documentation of transitional cell carcinoma of the urothelium (including the urinary bladder, ureter, urethra and renal pelvis) of the urinary tract (cystoscopy and biopsy or positive cytology). 4. Patients must have confirmed cT2-T4 N0-1 M0 (TNM classification). 5. Archival tumour samples for biomarker research in formalin-fixed and paraffin-embedded blocks. 6. Body weight >30kg 7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 8. Life expectancy of at least 12 weeks 9. Adequate organ function as determined by: a) Hematological (without growth factor or transfusion support within 28 days prior to first dose of investigational product)
  • Absolute neutrophil count (ANC) ≥ 1500/mm3 (≥ 1.5 GI/L).
  • Platelets ≥ 100,000/mm3 (≥ 100 GI/L)
  • Hemoglobin ≥ 9 g/dL (≥ 90 g/L) 10. Hepatic: 1. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 x upper limit of normal unless liver metastases are present, in which case it must be ≤5x ULN. 2. Total bilirubin ≤ 1.5 × the upper limit of normal. For subjects with Gilbert's disease ≤ 3 mg/dL (≤ 51.3 μmol/L). 11. Renal: a) Calculated CrCl or 24-hour urine CrCl>40 mL/min or Calculated creatinine clearance CL>40 mL/min by the Cockcroft-Gault formula or by 24-hour urine collection for determination of creatinine clearance 12. Fasting serum triglycerides ≤ 2.5 × upper limit of normal AND total cholesterol ≤ 300 mg/dL (≤ 7.75 mmol/L). Lipid-lowering medication is allowed. 13. HbA1c ≤ 8%. 14. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause.

Exclusion Criteria:

  • 1. Histology of pure adenocarcinoma, pure squamous cell carcinoma, or predominant small cell carcinoma or sarcomatoid features in the tumor sample. 2. Evidence of any metastatic lesion outside the primary tumour site identified in the radiological evaluation. 3. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab. The following are exceptions to this criterion:
  • Intranasal, inhaled, topical steroids or local steroid injections (eg, intra-articular injection).
  • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent.
  • Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication). 4. Previous therapy with PD-1, PD-L1 or CTLA-4 inhibitors, including durvalumab and tremelimumab. 5. Any concurrent chemotherapy, immunotherapy (IMT), or biologic or hormonal therapy for cancer treatment. Concurrent use of hormones for non-cancer-related conditions (eg, insulin for diabetes and hormone replacement therapy) is acceptable. 6. History of severe allergic reactions (ie, Grade 4 allergy, anaphylactic reaction from which the subject did not recover within 6 hours of institution of supportive care) to any unknown allergens or any components of the study drug formulations. 7. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion:
  • Patients with vitiligo or alopecia
  • Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
  • Any chronic skin condition that does not require systemic therapy
  • Patients without active disease in the last 5 years may be included but only after consultation with the study physician
  • Patients with celiac disease controlled by diet alone 8. Major surgery within 4 weeks of study randomization. 9. Prior high-dose chemotherapy requiring hematopoietic stem cell rescue. 10. Prior radiation therapy to >25% of the bone marrow. 11. Current treatment on another clinical trial. 12. Diagnosis of any second malignancy within the last 3 years, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix. 13. Any of the following within the 12 months prior to starting study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, cerebrovascular accident including transient ischemic attack, or pulmonary embolus. 14. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms calculated from 3 electrocardiograms (ECGs). 15. Any unresolved toxicity National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
  • Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
  • Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the Study Physician. 16. Hypertension that cannot be controlled by medications (>150/100 mmHg despite optimal medical therapy) 17. Current treatment with therapeutic doses of Coumadin (low dose Coumadin up to 2 mg PO daily for deep vein thrombosis prophylaxis is allowed). 18. History of active primary immunodeficiency 19. Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis (TB) testing in line with local practice), hepatitis B (known positive hepatitis B virus (HBV) surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV Ribonucleic acid (RNA). 20. Known positive for human immunodeficiency virus (HIV), chronic or active hepatitis B or C or active hepatitis A. 21. Receipt of live, attenuated vaccine within 30 days prior to the first dose of investigational products. 22. Pregnancy or breastfeeding. All female patients with reproductive potential must have a negative pregnancy test (serum or urine) prior to randomization. 23. Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration, or which, in the judgment of the investigator, would make the patient inappropriate for entry into this study. 24. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent 25. History of leptomeningeal carcinomatosis

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A Prospective, Single Arm, Multicenter, Phase II-Trial to Assess Safety and Efficacy of Preoperative RAdiation Therapy Before Radical CystEctomy Combined With ImmunoTherapy in Locally Advanced Urothelial Carcinoma of the Bladder


Condition: Urinary Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03529890

Sponsor: Technische Universität München

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • 1. Histologically confirmed, locally advanced bladder cancer (cT3/4 cN0/N+ cM0) 1. Urothelial cancer with at least 10% urothelial differentiation (excluding presence of small cell differentiation, which is not allowed in any percentage) 2. Histologic proof of muscle invasion in TUR-B specimen: ≥ pT2 3. Signs of locally advanced bladder cancer (at least one of the following must apply): i. cT3/4 in imaging studies (bladder wall thickening or infiltration of perivesical fat/adjacent organs) ii. Presence of hydronephrosis (or status post nephrostomy/ureteral stent due to hydronephrosis) iii. Pelvic lymph nodes ≥ 8 mm in short axis 2. Ineligibility for neoadjuvant cisplatin-based chemotherapy due to any of the following criteria: 1. Creatinine Clearance (using the Cockcroft-Gault formula) < 60 mL/min 2. Hearing loss ≥ grade 2 (CTCAE version 4) 3. Peripheral neuropathy ≥ grade 2 (CTCAE version 4) 4. ECOG performance score 2 3. Subjects that are eligible for cisplatin may be candidates if they refuse available neoadjuvant cisplatin-based chemotherapy, despite being informed by the investigator about the treatment options. The subject's refusal must be thoroughly documented. 4. Eligible for radical cystectomy 5. ECOG 0
  • 2 6. Estimated life expectancy > 6 months 7. Adequate function of bone marrow, liver and kidney: 1. WBC ≥ 2000/μL 2. Neutrophils ≥ 1500/μL 3. Platelets ≥ 100 × 103/μL 4. Hemoglobin ≥ 9.0 g/dL 5. AST ≤ 3 × ULN 6. ALT ≤ 3 × ULN 7. Total bilirubin ≤ 1.5 × ULN (except in participants with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL) 8. GFR ≥ 15 mL/min without hydronephrosis. In case of hydronephrosis, drainage should be performed prior to inclusion preferably by nephrostomy, alternatively by ureteral stent placement. Use measured creatinine-clearance or estimated clearance (Cockcroft-Gault formula): 9. Female CrCl = [(140
  • age in years) × weight in kg × 0.85] / [72 x serum creatinine in mg/dL] ii. Male CrCl = [(140
  • age in years) × weight in kg × 1.00] / [72 x serum creatinine in mg/dL] 8. Informed consent: 1. Participants must have signed and dated an IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal participant care. 2. Participants must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, and other requirements of the study 9. Body weight 35 kg
  • 160 kg 10. Female patients with childbearing potential must have a negative serum pregnancy test prior to start of trial. 11. Women of childbearing potential (WOCBP) and men (who are sexually active with WOCBP) must use any contraceptive method with a failure rate of less than 1% per year (see Appendix 15.7). These patients will be instructed to adhere to contraception for the period between inclusion into the study and surgery (which leads to sterility). Women who are not of childbearing potential (i.e. who are postmenopausal or surgically sterile) as well as sterile men do not require contraception. If patients do not undergo surgery or in the rare case of fertility preserving cystectomy , effective contraception should be used for at least 5 months following the last dose of Nivolumab. In the latter instance serum pregnancy testing is required in WOCBP at the end of the 5 months.

Exclusion Criteria:

  1. Metastatic disease defined as distant metastasis or suspicious lymph nodes (> 10mm short axis) outside the pelvis (clearly above aortic bifurcation) using RECIST 1.1 criteria. Enlarged lymph nodes in the pelvis below or at aortic bifurcation are NO exclusion criterion irrespective of size.
  2. Prior chemotherapy before treatment (not including intravesical chemotherapy)
  3. Prior radiation therapy of the pelvis
  4. Active, known or suspected autoimmune disease (not including: vitiligo, allergic rhinitis/asthma, type 1 diabetes mellitus, residual hypothyroidism due to an autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger)
  5. Immunosuppressive treatment with corticosteroids or other drugs within 14 days of study drug administration (not including: inhaled or topical steroids and adrenal replacement doses are permitted in the absence of active autoimmune disease)
  6. Experimental therapy or clinical trial at time of inclusion or the previous 4 weeks
  7. Previous treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways (not including BCG therapy)
  8. Any uncontrolled or severe cardiovascular or pulmonary disease determined by the investigator, including i) NYHA functional classification III or IV, congestive heart failure, unstable or poorly controlled angina, uncontrolled hypertension, serious arrhythmia or myocardial infarction in previous 12 months before inclusion; ii) Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxic.
  9. End-stage kidney disease defined as GFR < 15ml/min or need for dialysis in absence of hydronephrosis. In case of hydronephrosis, drainage should be performed prior to inclusion preferably by nephrostomy, alternatively by ureteral stent placement.
  10. Thromboembolic events like pulmonary embolism or apoplexy in previous 3 months
  11. Other active tumor disease (not including basal cell carcinoma of the skin, carcinoma in situ of the cervix and incidental prostate carcinoma). Tumor is regarded non active after curative therapy and 5 years of follow up without pathological findings.
  12. Medium to extended surgery or trauma in the previous 4 weeks (not including transurethral bladder resection, nephrostomy or ureteral stent or biopsy)
  13. Uncontrolled and serious somatic or mental illness
  14. Age < 18 years
  15. Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.
  16. Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities [§ 40 Abs. 1 S. 3 Nr. 4 AMG].
  17. Patients who are unable to consent because they do not understand the nature, significance and implications of the clinical trial and therefore cannot form a rational intention in the light of the facts [§ 40 Abs. 1 S. 3 Nr. 3a AMG].
  18. Female subjects who are pregnant, breast-feeding or male/female patients of childbearing potential who are not employing an effective method of birth control (failure rate of less than 1% per year). [Acceptable methods of contraception are: implants, injectable contraceptives, combined oral contraceptives, intrauterine pessaries (only hormonal devices), sexual abstinence or vasectomy of the partner, see Appendix 15.7.].
  19. Participation in another clinical study with an investigational product during the last 30 days before inclusion or 7 half-lifes of previously used trial medication, whichever is longer.
  20. Hypersensitivity to Nivolumab or any of it's excipients.
  21. Prior organ transplantation
  22. Positive test result for hepatitis B or C indicating acute or chronic infection.
  23. Positiv HIV test or acquired immunodeficiency syndrome (AIDS)
  24. Serious or uncontrolled medical disorder or active infection that, in the opinion of the investigator, may increase the risk associated with study participation, study drug administration, or would impair the ability of the patient to receive protocol therapy
  25. Gastrointestinal disorders, particularly those with high risk of perforation or fistula formation including i) active peptic ulcer disease or active inflammatory bowel disease (incl. ulcerative colitis and Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis during screening and/or ii) history of abdominal fistula or bowel perforation within 6 months prior to first dose of study treatment.

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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 Cortex 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, Cervical Clear Cell 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, 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, 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, Pituitary Gland Carcinoma, 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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Pioglitazone and Risk of Bladder Cancer in Patients With Type 2 Diabetes Mellitus"PROBE-PIO"Study


Condition: Bladder Cancer

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT01935466

Sponsor: Postgraduate Institute of Medical Education and Research

Phase:

Eligibility:

  • Age: minimum 50 Years maximum N/A
  • Gender: Male

Inclusion Criteria:

  1. Male Type 2 diabetes subjects with age >50 year
  2. On anti-diabetic drugs and/or insulin for≥ 1 year
  3. Patient willing to provide informed consent to be included in the study

Exclusion Criteria:

  • 1. Bladder cancer diagnosed before the onset of Diabetes mellitus. 2. Patient not willing to participate in the study.

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


Condition: Advanced Bladder Carcinoma, Advanced Urothelial Carcinoma, Metastatic Bladder Urothelial Carcinoma, Metastatic Urothelial Carcinoma, Stage III Bladder Cancer AJCC v8, Stage IIIA Bladder Cancer AJCC v8, Stage IIIB Bladder Cancer AJCC v8, Stage IV Bladder Cancer AJCC v8, Stage IVA Bladder Cancer AJCC v8, Stage IVB 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 of urothelial carcinoma of the urothelial tract/bladder 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 and Foundation Liquid results performed prior to enrollment on this study may be accepted for eligibility review): 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
  • 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 tumor sample for mutation analysis or be willing to undergo mandatory screening biopsy
  • 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)

View trial on ClinicalTrials.gov


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Transurethral En Bloc Versus Standard Resection of Bladder Tumour: A Multi-centre Randomised Controlled Trial (EB-StaR Study).


Condition: Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02993211

Sponsor: Chinese University of Hong Kong

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

  • Age ≥ 18 years old with informed consent

Exclusion Criteria:

  • Bladder tumour base with maximal dimension of >3cm (Anticipated difficulty in retrieving the specimen en bloc)
  • Bladder tumour detected during intravesical BCG therapy (BCG failure warrants more aggressive treatment, i.e. radical cystectomy)
  • Histological diagnosis other than NMIBC
  • Presence or prior history of upper urinary tract malignancy
  • ECOG performance status ≥ 3 (Confined to bed or chair more than 50% of waking hours)
  • ASA III or above (Patient with severe systemic disease)
  • History of bleeding disorder or use of anti-coagulants
  • Pregnancy
  • Presence of other active malignancy
  • Life expectancy of less than one year

View trial on ClinicalTrials.gov


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