Bladder Cancer

{{header-clinical-trials-navigation}}

Laser Versus Electrical Transurethral Enbloc Resection of Non-muscle Invasive Bladder Tumours: A Randomized Trial


Condition: Urinary Bladder Neoplasm

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04029948

Sponsor: Mansoura University

Eligibility:

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

Inclusion Criteria:

  1. Patients presented with visual criteria suggesting NMIBC by outpatient cystoscopy will be legible for inclusion

Exclusion Criteria:

  • 1. Tumor criteria 1. MIBC 2. Tumours deemed not legible for Enbloc resection as Judged by the surgeon e.g.
  • location: Tumour in diverticulum, at the anterior wall or close to ureteric orifice….etc
  • Wide base tumour 2. Patients criteria 1. Bleeding tendency 2. Synchronous either urethral tumours or upper urinary tract tumours 3. History of CIS 4. Contracted bladder

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

A Randomized Phase 3 Study Evaluating Cystectomy With Perioperative Pembrolizumab and Cystectomy With Perioperative Enfortumab Vedotin and Pembrolizumab Versus Cystectomy Alone in Participants Who Are Cisplatin-Ineligible or Decline Cisplatin With Muscle-Invasive Bladder Cancer (KEYNOTE-905/EV-303)


Condition: Urinary Bladder Cancer, Muscle-invasive

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03924895

Sponsor: Merck Sharp & Dohme LLC

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

  • Have a histologically confirmed diagnosis of urothelial carcinoma (cT2-T4aN0M0 or T1-T4aN1M0) with predominant (≥50%) urothelial histology to be confirmed by Blinded Independent Central Review (BICR) (central pathology and/or imaging).
  • Clinically nonmetastatic bladder cancer determined by imaging
  • Eligible for radical cystectomy (RC) + pelvic lymph node dissection (PLND), and agreement to undergo curative intent standard RC + PLND (including prostatectomy if applicable)
  • Ineligible for treatment with cisplatin, as defined by meeting at least one of the following criteria OR be eligible for treatment with cisplatin (by NOT meeting at least one of the following criteria) but decline treatment with cisplatin-based chemotherapy:
  • Impaired renal function with measured or calculated creatinine clearance (CrCl) 30 to 59 mL/min (calculated by Cockcroft-Gault method, Modification of Diet of Renal Disease [MDRD] equations, or measured by 24-hour urine collection)
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 2
  • Common Terminology Criteria for Adverse Events (CTCAE) v.4 Grade ≥2 audiometric hearing loss
  • New York Heart Association (NYHA) Class III heart failure
  • Transurethral resection (TUR) of a bladder tumor that is submitted for central pathology assessment and adequate to determine urothelial histology and PD-L1 expression assessment
  • ECOG performance status of 0, 1, or 2
  • Adequate organ function
  • A male participant is eligible to participate if he agrees to use contraception and refrain from donating sperm during the intervention period and for at least 180 days after the last dose of enfortumab vedotin. If the male participants are receiving pembrolizumab only or undergoing surgery only, there are no contraception requirements
  • A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies: Not a (woman of childbearing potential) WOCBP or a WOCBP who agrees to use a highly effective contraceptive method or be abstinent from heterosexual intercourse (as their preferred and usual lifestyle) during the intervention period and for at least 120 days after the last dose of pembrolizumab and at least 180 days after the last dose of enfortumab vedotin; whichever comes last. A female participant must agree not to donate eggs during this period as well
  • A WOCBP must have a negative highly sensitive pregnancy test within 24 hours before the first dose of study intervention

Exclusion Criteria:

  • Known additional nonurothelial malignancy that is progressing or has required active anticancer treatment ≤3 years of study randomization, with certain exceptions
  • Has ≥ N2 or metastatic disease (M1) as identified by imaging
  • Received any prior systemic treatment, chemoradiation, and/or radiation therapy for for muscle-invasive bladder cancer (MIBC) or non-muscle invasive bladder cancer (NMIBC)
  • Received prior therapy with an anti-programmed cell death protein 1 (PD-1), anti-programmed death-ligand 1 (PD-L1), or anti-programmed cell death 1 ligand 2 (PD-L2), or with an agent directed to another stimulatory or coinhibitory T-cell receptor
  • Received prior systemic anticancer therapy including investigational agents within 3 years prior to randomization
  • Received any prior radiotherapy to the bladder
  • Received a partial cystectomy of the bladder to remove any non-muscle-invasive bladder cancer (NMIBC) or MIBC
  • Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
  • Current participation in or participation in a study of an investigational agent or use of an investigational device within 4 weeks prior to the first dose of study intervention
  • Ongoing sensory or motor neuropathy Grade 2 or higher
  • Diagnosis of immunodeficiency or receipt of chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug. Physiologic replacement doses of corticosteroids are permitted for participants with adrenal insufficiency.
  • Hypersensitivity to monoclonal antibodies (including pembrolizumab) and/or any of their excipients
  • Severe hypersensitivity (≥ Grade 3) to enfortumab vedotin or any excipient contained in the drug formulation of enfortumab vedotin
  • Active keratitis or corneal ulcerations. Participants with superficial punctate keratitis are allowed if the disorder is being adequately treated in the opinion of the investigator
  • Active autoimmune disease that has required systemic therapy in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic therapy and is allowed
  • Has uncontrolled diabetes
  • History of (noninfectious) pneumonitis that required steroids, or current pneumonitis
  • Active infection requiring systemic therapy
  • Has had an allogenic tissue/solid organ transplant

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

CISTO: Comparison of Intravesical Therapy and Surgery as Treatment Options for Bladder Cancer


Condition: Bladder Cancer, Cancer of the Bladder, Recurrent, Non-muscle Invasive Bladder Cancer

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT03933826

Sponsor: University of Washington

Phase:

Eligibility:

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

Inclusion Criteria:

  1. Adult 18 years of age or older; and
  2. Presenting with high-grade NMIBC established by anatomic pathology as tumor stage classification Tis, Ta, or T1, and with:
  3. Pathology documentation from any hospital/clinic/medical center, and
  4. More than 50% urothelial carcinoma component in the specimen
  5. History of high-grade NMIBC established by anatomic pathology as tumor stage classification Tis, Ta, or T1; and
  6. Attempted or received induction BCG (at least 3 out of 6 instillations) at any point in time; and
  7. In the previous 12 months, received at least one instillation of any intravesical agent (induction or maintenance) or one administration of systemic therapy for NMIBC treatment. Patient Eligibility,

Exclusion Criteria:

  1. Any plasmacytoid or small cell (neuroendocrine) component in the pathology (past or current presentation);
  2. Previous history of cystectomy or radiation therapy for bladder cancer;
  3. Previous history of muscle-invasive bladder cancer or metastatic bladder cancer;
  4. Any history of upper tract urothelial carcinoma;
  5. Incarcerated in a detention facility or in police custody (patients wearing a monitoring device can be enrolled) at baseline/screening;
  6. Contraindication to radical cystectomy (e.g., ASA of 4);
  7. Contraindication to medical therapy (i.e., intolerant of all medical therapies);
  8. Unable to provide written informed consent in English;
  9. Unable to be contacted for research surveys;
  10. Planning to participate in a Phase I or Phase II interventional clinical trial for NMIBC or any blinded interventional trial for NMIBC.

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

A Phase I-II Study to Evaluate the Efficacy and Safety of Niraparib in Combination With Cabozantinib (XL184) in Patients With Advanced Urothelial Cancer After Failure to First-line Platinum-based Chemotherapy


Condition: Urothelial Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03425201

Sponsor: Fundacion CRIS de Investigación para Vencer el Cáncer

Phase: Phase 1/Phase 2

Eligibility:

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

Inclusion Criteria:

  • Phase I study: 1. Histologically confirmed UC of the urinary tract or renal cell carcinoma 2. Advanced or metastatic disease that is not amenable to curative surgery or radiation 3. Patients must be willing to provide a tumor specimen prior to enrollment 4. Previous therapy: i.Renal cell carcinoma: Prior tyrosine kinase inhibitor (TKI) and mechanistic target of rapamycin (mTOR) therapies is allowed ii.UC of the urinary tract: ≤2 previous chemotherapy regimens (including a platinum-based regimen) 5. Measurable disease will not be required 6. The remaining inclusion/exclusion criteria will be identical to the phase II study 7. Recovery to at least grade I from toxicities related to prior treatment unless non clinically significant or stable on supportive therapy Phase II study: 1. Age ≥18 years 2. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤1 3. Histologically confirmed UC of the bladder, urethra, ureter or renal pelvis (patients with mixed histologies will be allowed if urothelial is the predominant component). 4. Patients must have formalin-fixed paraffin-embedded (FFPE) tumor samples available from the primary or recurrent cancer or agree to undergo fresh biopsy prior to study treatment initiation 5. Advanced or metastatic disease that is not amenable to curative surgery or radiation 6. Prior treatment with one prior cytotoxic regimen of platinum-based chemotherapy. If the only prior cytotoxic therapy was administered in perioperative (ie, neoadjuvant or adjuvant) settings, the patient will be eligible provided the interval from end of therapy to the diagnosis of metastatic disease is less than one year. 7. Confirmed progressive disease after treatment with platinum-based chemotherapy 8. At least one measurable disease site that has not been previously irradiated 9. No prior therapy with Poly(ADP-ribose) polymerase (PARP) or c-Met inhibitors. 10. Prior anti programmed cell death protein 1 (PD1) and anti programmed death-ligand 1 (PD-L1) therapy is permitted 11. Adequate bone marrow, liver and renal functions as assessed by the following:
  • Hemoglobin ≥9 g/dL; absolute neutrophil count ≥1500 cells/µL; platelets ≥100,000 g/µL;
  • Total bilirubin ≤1.5 times upper limit of normal (ULN) (≤2.0 in patients with known Gilberts syndrome); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 times ULN unless liver metastases are present, in which case they must be ≤5x ULN.
  • Serum creatinine ≤1.5x ULN or creatinine clearance ≥30 mL/min using Cockcroft-Gault formula
  • Urine protein/creatinine ratio (UPCR) ≤1 mg/mg (113.2 mg/mmol) creatinine or 24-hr urine protein of <1 g 12. Life expectancy greater than 3 months 13. Patients must be able to take oral medications 14. Participant receiving corticosteroids may continue as long as their dose is stable for least 4 weeks prior to initiating protocol therapy. 15. Participant must agree to not donate blood during the study or for 90 days after the last dose of study treatment. 16. Female participant has a negative serum pregnancy test within 7 days prior to taking study treatment if of childbearing potential and agrees to abstain from activities that could result in pregnancy from screening through 180 days after the last dose of study treatment, or is of non-childbearing potential. Non-childbearing potential is defined as follows (by other than medical reasons):
  • ≥45 years of age and has not had menses for >1 year
  • Patients who have been amenorrhoeic for <2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation a. Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure, otherwise the patient must be willing to use 2 adequate barrier methods throughout the study, starting with the screening visit through 180 days after the last dose of study treatment. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient. 17. Participant must agree to not breastfeed during the study or for 180 days after the last dose of study treatment. 18. Male participant agrees to use an adequate method of contraception starting with the first dose of study treatment through 180 days after the last dose of study treatment. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient. 19. Participant must be able to understand the study procedures and agree to participate in the study by providing written informed consent Exclusion Criteria: 1. Participant must not be simultaneously enrolled in any interventional clinical trial 2. Major surgery, open biopsy or significant traumatic injury within 8 weeks prior to study entry and complete wound healing at the inclusion 3. Participant must not have received investigational therapy ≤ 4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is shorter, prior initiating protocol therapy. 4. Progressed while on platinum treatment or within 2 months from completion of platinum-containing regimen.

Exclusion Criteria:

  • will be identical to the phase II study 7. Recovery to at least grade I from toxicities related to prior treatment unless non clinically significant or stable on supportive therapy Phase II study: 1. Age ≥18 years 2. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤1 3. Histologically confirmed UC of the bladder, urethra, ureter or renal pelvis (patients with mixed histologies will be allowed if urothelial is the predominant component). 4. Patients must have formalin-fixed paraffin-embedded (FFPE) tumor samples available from the primary or recurrent cancer or agree to undergo fresh biopsy prior to study treatment initiation 5. Advanced or metastatic disease that is not amenable to curative surgery or radiation 6. Prior treatment with one prior cytotoxic regimen of platinum-based chemotherapy. If the only prior cytotoxic therapy was administered in perioperative (ie, neoadjuvant or adjuvant) settings, the patient will be eligible provided the interval from end of therapy to the diagnosis of metastatic disease is less than one year. 7. Confirmed progressive disease after treatment with platinum-based chemotherapy 8. At least one measurable disease site that has not been previously irradiated 9. No prior therapy with Poly(ADP-ribose) polymerase (PARP) or c-Met inhibitors. 10. Prior anti programmed cell death protein 1 (PD1) and anti programmed death-ligand 1 (PD-L1) therapy is permitted 11. Adequate bone marrow, liver and renal functions as assessed by the following:
  • Hemoglobin ≥9 g/dL; absolute neutrophil count ≥1500 cells/µL; platelets ≥100,000 g/µL;
  • Total bilirubin ≤1.5 times upper limit of normal (ULN) (≤2.0 in patients with known Gilberts syndrome); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 times ULN unless liver metastases are present, in which case they must be ≤5x ULN.
  • Serum creatinine ≤1.5x ULN or creatinine clearance ≥30 mL/min using Cockcroft-Gault formula
  • Urine protein/creatinine ratio (UPCR) ≤1 mg/mg (113.2 mg/mmol) creatinine or 24-hr urine protein of <1 g 12. Life expectancy greater than 3 months 13. Patients must be able to take oral medications 14. Participant receiving corticosteroids may continue as long as their dose is stable for least 4 weeks prior to initiating protocol therapy. 15. Participant must agree to not donate blood during the study or for 90 days after the last dose of study treatment. 16. Female participant has a negative serum pregnancy test within 7 days prior to taking study treatment if of childbearing potential and agrees to abstain from activities that could result in pregnancy from screening through 180 days after the last dose of study treatment, or is of non-childbearing potential. Non-childbearing potential is defined as follows (by other than medical reasons):
  • ≥45 years of age and has not had menses for >1 year
  • Patients who have been amenorrhoeic for <2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation a. Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure, otherwise the patient must be willing to use 2 adequate barrier methods throughout the study, starting with the screening visit through 180 days after the last dose of study treatment. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient. 17. Participant must agree to not breastfeed during the study or for 180 days after the last dose of study treatment. 18. Male participant agrees to use an adequate method of contraception starting with the first dose of study treatment through 180 days after the last dose of study treatment. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient. 19. Participant must be able to understand the study procedures and agree to participate in the study by providing written informed consent Exclusion Criteria: 1. Participant must not be simultaneously enrolled in any interventional clinical trial 2. Major surgery, open biopsy or significant traumatic injury within 8 weeks prior to study entry and complete wound healing at the inclusion 3. Participant must not have received investigational therapy ≤ 4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is shorter, prior initiating protocol therapy. 4. Progressed while on platinum treatment or within 2 months from completion of platinum-containing regimen. Exclusion criteria applicable only to patients included in phase II. 5. Radiation therapy for bone or brain metastases within 4 weeks before first dose of study drug. Other external radiation within 4 weeks before first dose of study drug. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible 6. Participant must not have a known hypersensitivity to niraparib or cabozantinib components or excipients. 7. Participant must not have received a transfusion (platelets or red blood cells) ≤ 4 weeks prior to initiating protocol therapy. 8. Participant must not have received colony stimulating factors (eg, granulocyte colony-stimulating factor, granulocyte macrophage colony stimulating factor, or recombinant erythropoietin) within 4 weeks prior initiating protocol therapy. 9. Participant has had any known Grade 3 or 4 anemia, neutropenia or thrombocytopenia due to prior chemotherapy that persisted > 4 weeks and was related to the most recent treatment. 10. Known history of myelodysplastic syndrome (MDS) or a pre-treatment cytogenetic testing result at risk for a diagnosis of MDS/acute myeloid leukemia (AML) 11. Unstable systemic disease or active uncontrolled infection 12. Any concurrent active malignancy requiring treatment (other than basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or malignancies curatively treated > 3 years prior to study entry) 13. Known uncontrolled symptomatic brain or leptomeningeal metastases or cranial epidural disease; subjects with brain metastases previously treated and on stable dose of corticosteroids and/or anticonvulsants for >4 weeks, or not requiring such medications, are eligible. Baseline brain scans are not required to confirm eligibility. 14. Uncontrolled hypertension 15. Significant cardiovascular diseases, clinically relevant cardiac arrhythmia, unstable angina or myocardial infarction within 6 months prior to randomization, congestive heart failure > New York Heart Association (NYHA) III, severe peripheral vascular disease, QT prolongation >470 msec ,clinically significant pericardial effusion 16. Receiving concomitant medications that prolong corrected QT and is unable to discontinue use 17. Concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, heparin, thrombin or Factor Xa inhibitors, or antiplatelet agents (eg, clopidogrel). Low dose aspirin (≤ 100 mg/day), low-dose warfarin (≤ 1 mg/day), and prophylactic low molecular weight heparin (LMWH) are permitted 18. Prothrombin time (PT)/international normalized ratio (INR) or partial thromboplastin time (PTT) test ≥1.3 x ULN within 7 days before the first dose of study treatment 19. Significant thromboembolic or vascular disorders within 6 months prior to administration of study drugs, including:
  • Symptomatic pulmonary embolism
  • Cerebrovascular accident
  • Peripheral arterial ischemia > grade 2
  • Coronary or peripheral artery bypass graft 20. The subject has experienced any of the following within 3 months before the first dose of study treatment:
  • clinically significant hematemesis or gastrointestinal bleeding
  • clinically significant hemoptysis 21. Any malabsorption problem that, in the investigator's opinion, would prevent adequate absorption of the study drug 22. Patient has not recovered to baseline or CTCAE ≤ Grade 1 from toxicity due to all prior therapies except alopecia and other non-clinically significant Adverse Events 23. History of organ transplant 24. Concurrent uncompensated hypothyroidism or thyroid dysfunction within 7 days before the first dose of study treatment 25. Active infection requiring systemic treatment within 28 days before the first dose of study treatment 26. Serious non-healing wound/ulcer/bone fracture within 28 days before the first dose of study treatment 27. Gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including:
  • Any of the following within 28 days before the first dose of study treatment: intra-abdominal tumor/metastases invading gastrointestinal mucosa, active peptic ulcer disease,inflammatory bowel disease (including ulcerative colitis and Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis
  • Any of the following within 6 months before the first dose of study treatment: History of abdominal fistula, gastrointestinal perforation, bowel obstruction or gastric outlet obstruction or intra-abdominal abscess 28. Chronic concomitant treatment of strong cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, and St. John's Wort)

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

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 aberration (FGFR1, FGFR2, or FGFR3 mutations / short variants 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

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

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

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

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

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

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

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

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.

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

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

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

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


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

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT02379429

Sponsor: National Cancer Institute (NCI)

Phase:

Eligibility:

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

Inclusion Criteria:

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

Exclusion Criteria:

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

Eligibility Criteria:

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

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

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

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

Optimized Perioperative Antibiotic Prophylaxis in Radical Cystectomy


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

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03305627

Sponsor: University Hospital Inselspital, Berne

Eligibility:

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

Inclusion Criteria:

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

Exclusion Criteria:

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

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

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

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

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

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02834013

Sponsor: National Cancer Institute (NCI)

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

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

Eligibility Criteria:

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

Exclusion Criteria:

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

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

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


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

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


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

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


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

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03513952

Sponsor: National Cancer Institute (NCI)

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

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

Exclusion Criteria:

  • Patients with prior allogeneic bone marrow transplantation or prior solid organ transplantation
  • Patients who have had chemotherapy or radiotherapy within 2 weeks (4 weeks for nitrosoureas or systemic mitomycin C) before the initiation of study treatment
  • Patients who have received more than 2 systemic cytotoxic chemotherapy regimens for metastatic urothelial carcinoma
  • Note: Prior perioperative chemotherapy is allowed and is not counted as a line of therapy if patient relapsed >= 12 months later and received additional platinum-based chemotherapy for metastatic disease
  • Patients who have not recovered from adverse events (other than alopecia) due to agents administered more than 4 weeks earlier (i.e., have residual toxicities > grade 1); however, the following therapies are allowed:
  • Hormone-replacement therapy or oral contraceptives
  • Herbal therapy >= 1 week before initiation of study treatment (herbal therapy intended as anticancer therapy must be discontinued at least 1 week before initiation of study treatment)
  • Palliative radiotherapy for bone metastases > 2 weeks before initiation of study treatment
  • Patients who have received prior treatment with anti-PD-1, or anti-PD-L1 therapeutic antibody, or pathway -targeting agents
  • Patients who have received prior treatment with anti-CTLA-4 may be enrolled, provided the following requirements are met:
  • Minimum of 12 weeks from the first dose of anti-CTLA-4 and > 6 weeks from the last dose
  • No history of severe immune-related adverse effects from anti-CTLA-4 (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] grade 3 and 4)
  • Patients who have received treatment with any other investigational agent within 4 weeks before initiation of study treatment
  • Patients who have received treatment with systemic immunostimulatory agents (including, but not limited to, interferon [IFN]-alpha or interleukin [IL]-2) within 6 weeks before initiation of study treatment
  • Patients who have received treatment with systemic immunosuppressive medications (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti TNF] agents) within 2 weeks before initiation of study treatment
  • Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled
  • The use of inhaled corticosteroids, and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed
  • Patients taking bisphosphonate therapy for symptomatic hypercalcemia
  • Note: Use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed
  • Patients with known primary central nervous system (CNS) malignancy or symptomatic CNS metastases are excluded, with the following exceptions:
  • Patients with asymptomatic untreated CNS disease may be enrolled, provided all of the following criteria are met:
  • Evaluable or measurable disease outside the CNS
  • No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm)
  • No history of intracranial hemorrhage or spinal cord hemorrhage
  • No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted
  • No neurosurgical resection or brain biopsy within 28 days before initiation of study treatment
  • Patients with asymptomatic treated CNS metastases may be enrolled, provided all the criteria listed above are met as well as the following:
  • Radiographic demonstration of improvement upon the completion of CNS directed therapy and no evidence of interim progression between the completion of CNS directed therapy and the screening radiographic study
  • No stereotactic radiation or whole-brain radiation within 28 days before initiation of study treatment
  • Screening CNS radiographic study >= 4 weeks from completion of radiotherapy and >= 2 weeks from discontinuation of corticosteroids
  • Note: Patients with CNS metastases enrolled on trial must also have a brain MRI imaging at all standard radiologic evaluation timepoints
  • Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
  • Patients who have a history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  • Patients with known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver/nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH); and inherited liver disease
  • Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBc [antibody to hepatitis B core antigen] antibody test) are eligible
  • Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA)
  • Patient who have a history or risk of autoimmune disease, including, but not limited to, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis
  • Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid-replacement hormone may be eligible
  • Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen may be eligible
  • Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:
  • Patients with psoriasis must have a baseline ophthalmologic exam to rule out ocular manifestations
  • Rash must cover less than 10% of body surface area (BSA)
  • Disease is well controlled at baseline and only requiring low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, fluocinolone 0.01%, desonide 0.05%, alclometasone dipropionate 0.05%)
  • No acute exacerbations of underlying condition within the last 12 months (not requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids)
  • Patients who have a history of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest CT scan; history of radiation pneumonitis in the radiation field (fibrosis) is permitted
  • Patients who have known additional malignancies other than UBC within 2 years before initiation of study treatment; exceptions include malignancies with a negligible risk of metastasis or death and treated with expected curative outcome (e.g., non-melanomatous skin cancers), or localized prostate cancer treated with curative intent and absence of prostate-specific antigen (PSA) relapse or incidental prostate cancer
  • Patients with active tuberculosis (TB)
  • Patients who have leptomeningeal disease
  • Patients who have severe infections within 4 weeks before initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia;
  • Exception: Uncomplicated urinary tract infection will not be considered as a severe infection in these patients
  • Patients who have signs or symptoms of infection within 2 weeks before initiation of study treatment
  • Patients who have received oral or IV antibiotics within 2 weeks before initiation of study treatment; patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible
  • Patients who have major surgical procedure, other than for diagnosis, within 28 days before initiation of study treatment or anticipation of need for a major surgical procedure during the course of the study
  • Patients who have had a live, attenuated vaccine within 4 weeks before initiation of study treatment or anticipation that such a live, attenuated vaccine will be required during the study and up to 5 months after the last dose of atezolizumab.
  • Influenza vaccination should be given during influenza season only (approximately October to March); patients must not receive live, attenuated influenza vaccine within 4 weeks before initiation of study treatment or at any time during the study
  • Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure (New York Heart Association class III or IV), unstable angina pectoris, cardiac arrhythmia, recent myocardial infarction (within the last 6 months), or psychiatric illness/social situations that would limit compliance with study requirements
  • Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or medical (e.g., infectious) illness

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

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


Condition: Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03799835

Sponsor: UNICANCER

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

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

Exclusion Criteria:

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

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

Afatinib Dimaleate in Treating Patients With Advanced Refractory Urothelial Cancer


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

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02122172

Sponsor: University of Chicago

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

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

Exclusion Criteria:

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

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
email news signup