Bladder Cancer

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A Phase 3, Randomized Study of Adjuvant Cretostimogene Grenadenorepvec Versus Observation for the Treatment of Intermediate Risk Non-Muscle Invasive Bladder Cancer (IR-NMIBC) Following Transurethral Resection of Bladder Tumor (TURBT)


Condition: Non Muscle Invasive Bladder Cancer, Urologic Cancer, Bladder Cancer, Urothelial Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT06111235

Sponsor: CG Oncology, Inc.

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

  • Pathologically confirmed IR-NMIBC, per American Urologic Association/Society of Urologic Oncology/National Comprehensive Cancer Network guidelines, within 12 weeks of participant randomization: 1. Recurrent LG Ta within 12 months of prior LG or HG (HG Ta ≤ 3 cm) tumor 2. Solitary LG Ta >3 cm tumor 3. Multifocal LG Ta tumors 4. Primary and solitary HG Ta ≤3 cm tumor 5. LG T1 tumor
  • All visible disease removed by TURBT within 12 weeks of study randomization
  • Acceptable baseline organ function

Exclusion Criteria:

  • High-risk NMIBC (e.g., HG T1, Recurrent or multifocal HG Ta>3cm tumor(s), CIS)
  • Low-Risk NMIBC (e.g., solitary LG Ta ≤3 cm tumor)
  • Disease in the prostatic urethra at any time or in the upper genitourinary tract within 24 months of randomization
  • Muscle-invasive bladder cancer, locally advanced or metastatic bladder cancer
  • Prior treatment with any human adenovirus serotype 5 based therapy (e.g., Ad-interferon or Adstiladrin)

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A Phase I/II Open-Label Multicenter Study to Evaluate the Safety and Efficacy of Oral APL-1202 in Combination With Tislelizumab Compared to Tislelizumab Alone as Neoadjuvant Therapy in Patients With Muscle Invasive Bladder Cancer (MIBC)


Condition: Muscle Invasive Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04813107

Sponsor: Jiangsu Yahong Meditech Co., Ltd aka Asieris

Phase: Phase 1/Phase 2

Eligibility:

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

Inclusion Criteria:

  • 1. Willing and able to provide written informed consent. 2. Age ≥ 18 years. 3. Histopathologically confirmed transitional cell carcinoma of the bladder. Patients with mixed histologies are required to have a dominant (i.e. > 50%) transitional cell pattern. 4. Radical cystectomy is planned (according to local guidelines). 5. Patients who refuse neoadjuvant cisplatin based chemotherapy or in whom neoadjuvant cisplatin based therapy is contraindicated. Contraindications to cisplatin is defined by meeting at least one of the following criteria:
  • Impaired renal function with calculated CrCl 30 to 59 mL/min (by Cockcroft-Gault equation).
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 2.
  • CTCAE v.5 Grade ≥2 audiometric hearing loss.
  • In the clinical judgement of the investigator, potential adverse effects from cisplatin-based neoadjuvant chemotherapy outweighs its benefits. 6. Clinical stage T2-T4a N0 M0 disease by CT (or MRI) (within 4 weeks of randomization). 7. Residual disease after transurethral resection of bladder (TURB) (surgical opinion, cystoscopy or radiological presence). 8. Availability of representative formalin-fixed paraffin-embedded (FFPE) tumor specimens or unstained slides, with an associated pathology report, and determined to be evaluable for tumor PD-L1 expression prior to study enrollment; 9. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2. 10. Adequate hematologic and end-organ functions:
  • Hemoglobin > 9.0 g/dL;
  • Absolute neutrophil count (ANC) > 1.5×109 /L;
  • Platelet count > 100×109 /L;
  • Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN).
  • Aspartate aminotransferase (AST) /alanine aminotransferase (ALT) ≤ 2.5 x institutional upper limit of normal ULN.
  • CrCl (calculated using Cockcroft-Gault equation) ≥ 30 mL/min (calculated CrCl ≥ 50 mL/min in Phase Ⅰ: Dose-Escalation).
  • INR < 1.5. This applies only to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose. 11. Female patients should be surgically sterilized or post-menopausal or must agree to take effective contraceptive measures during the treatment. Male patients must be surgically sterilized or must agree to take effective contraceptive measures during treatment. Patients must continue to take contraceptive measures for 3 months after the investigational therapy was completed.

Exclusion Criteria:

  1. Previous systemic therapy for bladder cancer.
  2. Malignancies other than urothelial bladder cancer within 5 years prior to cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ of breast treated surgically with curative intent).
  3. Evidence of measurable nodal or metastatic disease.
  4. Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including significant liver disease (such as cirrhosis, uncontrolled major seizure disorder, or superior vena cava syndrome).
  5. Pregnant female patients. All female patients with a positive pregnancy test within 2 weeks prior to the first dose of study treatment will be excluded from the study.
  6. Significant cardiovascular disease, such as New York Heart Association cardiac disease (more than Class II), myocardial infarction within 3 months prior to enrollment, unstable arrhythmias, or unstable angina.
  7. Severe infections within 4 weeks prior to enrollment in the study including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.
  8. Major surgical procedure within 4 weeks prior to enrollment or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis.
  9. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
  10. Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the tislelizumab or APL-1202 formulation.
  11. History of autoimmune disease 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.
  12. History of autoimmune-related hypothyroidism, unless on a stable dose of thyroid-replacement hormone.
  13. History of idiopathic pulmonary fibrosis.
  14. Uncontrolled Type 1 diabetes mellitus.
  15. Uncontrolled hypercalcemia (> 1.5 mmol/L ionized calcium or calcium > 12 mg/dL or corrected serum calcium > ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab.
  16. Prior allogeneic stem cell or solid organ transplantation.
  17. Positive test for HIV.
  18. Uncontrolled hepatitis infection.
  19. Active tuberculosis.
  20. Optic nerve disorders or with a history of optic nerve disorders.
  21. Cataract or with a history of cataract.
  22. Prior treatment with anti-programmed death-1 (PD-1), or anti-PD-L1 therapeutic antibody or pathway-targeting agents.
  23. Patients taking regular oral steroids, above the allowed limit of 10 mg/day methylprednisolone/prednisone or analogues, for any reason. Patients must not have had steroids for 4 weeks prior to study entry.
  24. Administration of vaccine within 4 weeks prior to enrollment or anticipation that such a vaccine will be required during the study.
  25. Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 4 weeks prior to enrollment.
  26. Treatment with systemic immunostimulatory agents within 4 weeks prior to enrollment.

View trial on ClinicalTrials.gov


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A Phase 1, Open-label, Dose-escalation Study to Investigate the Safety, Tolerability, and Pharmacokinetics of UGN-301 (Zalifrelimab) Administered Intravesically as Monotherapy and in Combination With Other Agents in Patients With Recurrent NMIBC


Condition: Non-muscle Invasive Bladder Cancer, NMIBC, Carcinoma in Situ of Bladder, Bladder Cancer, Urothelial Carcinoma Bladder, Urothelial Carcinoma Recurrent

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05375903

Sponsor: UroGen Pharma Ltd.

Phase: Phase 1

Eligibility:

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

Inclusion Criteria:

  • 1. Able to give informed consent. 2. Arm A: Have confirmed recurrent NMIBC with HG Ta and/or T1 disease and/or CIS or recurrent IR LG Ta and/or T1 disease. Arm B: Have confirmed recurrent NMIBC with HG Ta and/or T1 disease and/or CIS. Arm C: Have confirmed recurrent NMIBC with HG Ta and/or T1 disease and/or CIS. 3. Patients with HG Ta and/or T1 disease and/or CIS must meet one of the following criteria: • Have Bacillus Calmette-Guérin (BCG)-unresponsive disease, defined as 1) persistent or recurrent CIS alone or with recurrent Ta/T1 disease within 12 months of completion of adequate BCG therapy, or 2) recurrent HG Ta/T1 disease within 6 months of completion of adequate BCG therapy, or 3) HG T1 disease at the first evaluation following a BCG induction course. Notes: Adequate BCG therapy is defined as at least 5 of 6 doses of an initial induction course plus 1) at least 2 of 3 doses of maintenance therapy or 2) at least 2 of 6 doses of a second induction course. Patients with BCG-unresponsive disease also must be unwilling or unfit to undergo radical cystectomy.
  • Have otherwise failed adequate BCG therapy (eg, recurrence > 6 months [papillary] or > 12 months [CIS] after last BCG exposure).
  • Are BCG intolerant, defined as the inability to tolerate at least one full induction course of BCG.
  • Have HG Ta disease with tumors ≤ 3 cm and failed at least one previous course of therapy (eg, adjuvant intravesical chemotherapy). 4. Have all papillary tumors visible by white light resected, and obvious areas of CIS fulgurated during Screening or within 6 weeks before Screening. Note: Blue light cystoscopy is not permitted. 5. Eastern Cooperative Oncology Group (ECOG) status ≤ 2. 6. Absence of concomitant upper tract urothelial carcinoma (UTUC) or urothelial carcinoma (UC) within the prostatic urethra. Freedom from upper tract disease (if clinically indicated) as indicated by no evidence of upper tract tumor by either intravenous pyelogram, retrograde pyelogram, computerized tomography (CT) urogram with or without contrast, or magnetic resonance imaging (MRI) urogram with or without contrast performed within 6 months of enrollment. 7. Patients with prostate cancer on active surveillance at very low, low, or intermediate risk for progression, defined as Gleason Grade Group 1 or 2, Gleason score ≤ 7, with prostate-specific antigen < 20 ng/dL, and cT1-cT2b (NCCN, 2023) are permitted to be in the study at the discretion of the investigator (see exclusion criterion 8). 8. Female patients of childbearing potential must use maximally effective birth control during the period of therapy, must be willing to use contraception for 1 month following the last administration of study drug and must have a negative urine or serum pregnancy test upon entry into this study. Otherwise, female patients must be postmenopausal (no menstrual period for a minimum of 12 months) or surgically sterile. "Maximally effective birth control" means that the patient, if sexually active, should be using a combination of 2 methods of birth control that are approved and recognized to be effective by health authorities. 9. Male patients must be surgically sterile or willing to use 2 highly effective forms of birth control upon enrollment, during the course of the study, and for 1 month following the last study drug instillation. 10. Has adequate organ and bone marrow function within 14 days of treatment initiation as determined by routine laboratory tests outlined below:
  • Leukocytes ≥ 3,000/μL;
  • Absolute neutrophil count (ANC) ≥ 1,500/μL;
  • Platelets ≥ 100,000/μL;
  • Hemoglobin ≥ 9.0 g/dL;
  • Total bilirubin ≤ 1.5 × upper limit of normal (ULN);
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 × ULN;
  • Alkaline phosphatase (ALP) ≤ 2.5 × ULN;
  • Estimated creatinine clearance ≥ 30 mL/min calculated using the Cockcroft-Gault equation. 11. Has a life expectancy > 12 months.

Exclusion Criteria:

  1. Current or previous evidence of muscle invasive, locally advanced nonresectable, or metastatic urothelial carcinoma (ie, T2, T3, T4 and/or stage IV).
  2. Current systemic therapy for bladder cancer.
  3. Prior therapy with an anti-cytotoxic T lymphocyte antigen 4 (CTLA-4), anti-programmed cell death 1 (PD-1), anti-PD-ligand 1 (L1) agent, or with an agent directed to another co-inhibitory T-cell receptor.
  4. Active infection requiring systemic therapy including urinary tract infection (once satisfactorily treated, patients can enter the study).
  5. Active systemic autoimmune disease that required systemic treatment in the past 2 years. Short courses of steroids (≤ 14 days) for medical reasons without anticancer intent (eg, atopic dermatitis, psoriasis, infection, allergic reaction) are permitted if the last dose was ≥ 4 weeks before the first dose of study treatment.
  6. Women who are pregnant or nursing.
  7. Any medical psychological, familial, sociological, or geographical condition that, in the opinion of the Investigator, would preclude participation in the study.
  8. History of malignancy of other organ system within the past 5 years, except previously treated UTUC, basal cell carcinoma or squamous cell carcinoma of the skin, and/or prostate cancer under active surveillance (see inclusion criterion 8).
  9. Patients who cannot tolerate intravesical dosing or intravesical surgical manipulation.
  10. Intravesical therapy within 4 weeks before starting study treatment.
  11. Has participated in a study of an investigational agent and received study therapy or received investigational device within 4 weeks before the first dose of study treatment.
  12. Has received an immune modulator therapy within 5 half-lives of starting study treatment.
  13. Has received a vaccine within 2 weeks before starting study treatment.
  14. Has a known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.

View trial on ClinicalTrials.gov


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A Multicenter, Open-label Phase 1/2 Study of TYRA300 in Advanced Urothelial Carcinoma and Other Solid Tumors With Activating FGFR3 Gene Alterations (SURF301)


Condition: Locally Advanced Urothelial Carcinoma, Metastatic Urothelial Carcinoma, Solid Tumor, Urothelial Carcinoma, Solid Tumor, Adult, Bladder Cancer, Non-muscle-invasive Bladder Cancer, FGFR3 Gene Mutation, FGFR3 Gene Alteration, Advanced Solid Tumor, Advanced Urothelial Carcinoma, Urinary Tract Cancer, Urinary Tract Tumor, Urinary Tract Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05544552

Sponsor: Tyra Biosciences, Inc

Phase: Phase 1/Phase 2

Eligibility:

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

Inclusion Criteria:

  • Phase 1 Part A and Part B
  • Men and women 18 years of age or older.
  • Eastern Cooperative Oncology Group (ECOG) performance status of ≤1.
  • Histologically confirmed advanced solid tumor who have exhausted standard therapeutic options.
  • Evaluable (Part A) or measurable (Part B) disease according to RECIST v1.1.
  • Histologically confirmed advanced solid tumor with an eligible FGFR3 gene mutation or fusion (Part B). Phase 2
  • Men and women 12 years of age or older.
  • ECOG performance status of 0-2 or Karnofsky Performance Scale (KPS) >70 for participants aged 12 to 17 years.
  • At least 1 measurable lesion by RECIST v1.1.
  • Histologically confirmed locally advanced/metastatic tumor in one of the following categories:
  • Urothelial carcinoma with an eligible FGFR3 gene mutation or rearrangement who have progressed on a prior FGFR inhibitor and presence of a resistance mutation or other kinase domain mutation.
  • Urothelial carcinoma with an eligible FGFR3 gene mutation or rearrangement who has not received a prior FGFR inhibitor.
  • Any solid tumor with an eligible FGFR3 gene mutation or rearrangement.

Exclusion Criteria:

  • (All Phases):
  • Has a serum phosphorus level > upper limit of normal (ULN) during screening that remains >ULN despite medical management.
  • Any ocular condition likely to increase the risk of eye toxicity.
  • History of or current uncontrolled cardiovascular disease.
  • Active, symptomatic, or untreated brain metastases.
  • Gastrointestinal disorders that will affect oral administration or absorption of TYRA-300.
  • Females who are pregnant, breastfeeding, or planning to become pregnant and males who plan to father a child while enrolled in this study.

View trial on ClinicalTrials.gov


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An Open-Label, Multicenter Study of LOXO-435 (LY3866288) In Advanced Solid Tumor Malignancies With FGFR3 Alterations


Condition: Urinary Bladder Neoplasms, Neoplasm Metastasis, Ureteral Neoplasms

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05614739

Sponsor: Eli Lilly and Company

Phase: Phase 1

Eligibility:

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

Inclusion Criteria:

  • Have solid tumor cancer with an FGFR3 pathway alteration on molecular testing in tumor or blood sample that is deemed as actionable.
  • Cohort A1 (Dose Escalation): Presence of an alteration in FGFR3 or its ligands.
  • Cohort A2 (Dose Optimization): Histological diagnosis of urothelial cancer (UC) that is locally advanced or metastatic with a qualifying FGFR3 alteration.
  • Cohorts B1, B2 and B3 (Dose Expansion): Histological diagnosis of urothelial cancer that is locally advanced or metastatic with a prespecified activating FGFR3 alteration.
  • Cohort C (Dose Expansion): Must have histological diagnosis of a non-urothelial solid tumor malignancy that is locally advanced or metastatic with a prespecified activating FGFR3 alteration.
  • Measurability of disease:
  • Cohort A1: Measurable or non-measurable disease as defined by Response Evaluation Criteria in Solid Tumors v 1.1 (RECIST v1.1)
  • Cohorts A2, B1, B2, B3, and C1: Measurable disease required as defined by RECIST v1.1
  • Have adequate archival tumor tissue sample available or undergo a screening biopsy if allowed per country-specific regulations.
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Prior Systemic Therapy Criteria:
  • Cohort A1/C1: Participant has received all standard therapies for which the participant was deemed to be an appropriate candidate by the treating Investigator; OR the participant is refusing the remaining most appropriate standard of care treatment; OR there is no standard therapy available for the disease. There is no restriction on number of prior therapies.
  • Cohort A2/B1/B2/B3: Participants must have received at least one prior regimen in the advanced or metastatic setting. There is no restriction on number of prior therapies.
  • FGFR inhibitor specific requirements:
  • Cohort A1/A2: Prior FGFR inhibitor treatment is permitted, but not required.
  • Cohort B1: Participants must have been previously treated with a FGFR inhibitor.
  • Cohort B2, B3, C1: Participants must be FGFR inhibitor naïve.

Exclusion Criteria:

  • Participants with primary central nervous system (CNS) malignancy.
  • Known or suspected history of uncontrolled CNS metastases.
  • Current evidence of corneal keratopathy or retinal disorder.
  • Have a history and/or current evidence of extensive tissue calcification.
  • Any serious unresolved toxicities from prior therapy.
  • Significant cardiovascular disease.
  • Prolongation of the QT interval corrected for heart rate using Fridericia's formula (QTcF).
  • Active uncontrolled systemic infection or other clinically significant medical conditions.
  • Participants who are pregnant, lactating, or plan to breastfeed during the study or within 6 months of the last dose of study treatment. Participants who have stopped breastfeeding may be enrolled.

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Phase II Randomized Trial of Immunotherapy Versus Immunotherapy and Radiation Therapy for Platinum Ineligible/Refractory Metastatic Urothelial Cancer (IMMORTAL)


Condition: Metastatic Urothelial Carcinoma, Platinum-Resistant Urothelial Carcinoma, Stage IV Bladder Cancer AJCC v8

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04936230

Sponsor: National Cancer Institute (NCI)

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • PRE-REGISTRATION INCLUSION
  • Histologically confirmed metastatic urothelial carcinoma
  • Patients must be either ineligible for platinum treatment or platinum refractory as defined below:
  • Platinum-ineligible: If patients meet any one of the following criteria:
  • Impaired renal function (creatinine clearance [CrCl] of < 30 mL/min)
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of > 2
  • Grade > 2 peripheral neuropathy
  • New York Heart Association (NYHA) Heart Failure of > 3
  • Platinum-refractory: If patients meet any one of the following criteria:
  • Prior platinum-based perioperative chemotherapy within 12 months of relapse
  • Prior platinum-based chemotherapy for metastatic disease
  • Patients must have tissue available for central PD-L1 determination stratification OR agree to undergo a biopsy for additional tissue
  • Patients must have at least one measurable site >= 1 cm in diameter per RECIST 1.1 and a site targetable for radiotherapy. Measurable site must not overlap with radiated site such that measurable site cannot receive > 2 Gy per fraction
  • 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)
  • REGISTRATION INCLUSION
  • Men and women, ages >= 18 years of age
  • ECOG performance status =< 2
  • Leukocytes >= 2,500/mm^3
  • Absolute neutrophil count >= 1,500/mm^3
  • Platelets >= 100,000/mm^3
  • Hemoglobin >= 8 g/dL
  • Creatinine clearance (CrCl) of 30 to 59 mL/min
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (however, patients with known Gilbert disease who have serum bilirubin level =< 3 x ULN may be enrolled)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 3 x upper limit of normal (ULN)
  • AST and/or ALT =< 5 x ULN for patients with liver involvement
  • Alkaline phosphatase =< 2.5 x ULN
  • =< 5 x ULN for patients with documented liver involvement or bone metastases
  • Institutional 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
  • No prior allogeneic bone marrow transplantation or prior solid organ transplantation
  • No prior radiotherapy to targetable site or measurable site
  • No chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events (other than alopecia) due to agents administered more than 4 weeks earlier. However, the following therapies are allowed:
  • Hormone-replacement therapy or oral contraceptives
  • Palliative radiotherapy for bone metastases > 2 weeks prior to registration
  • No prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
  • No treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment
  • No prior treatment with any other investigational agent within 4 weeks prior to registration
  • No prior treatment with systemic immunostimulatory agents (including, but not limited to, interferon [IFN]-alpha or interleukin [IL]-2) within 6 weeks prior to registration
  • Any prior systemic therapy is permitted except therapy with PD1/PDL1 inhibitor
  • 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
  • No active tuberculosis (TB)
  • No known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
  • 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 prior to registration
  • Screening CNS radiographic study >= 4 weeks from completion of radiotherapy and >= 2 weeks from discontinuation of corticosteroids
  • No active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
  • Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone are eligible
  • No known history of, or any evidence of active, non-infectious pneumonitis or colitis
  • No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
  • No history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  • No known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease
  • No history of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted
  • No significant cardiovascular disease (such as New York Heart Association class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
  • No other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
  • No history of leptomeningeal disease
  • No uncontrolled tumor-related pain
  • Patients requiring pain medication must be on a stable regimen at study entry
  • Symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement) amenable to palliative radiotherapy should be treated prior to enrollment. Patients should be recovered from the effects of radiation. There is no required minimum recovery period
  • Asymptomatic metastatic lesions that would likely cause functional deficits or intractable pain with further growth (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for loco-regional therapy if appropriate prior to enrollment
  • No uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). Patients with indwelling catheters (e.g., PleurX) are allowed
  • Patients with controlled type 1 diabetes mellitus on a stable insulin regimen are 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%, flucinolone 0.01%, desonide 0.05%, aclometasone 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)
  • No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • No active infections requiring systemic antibiotics within 2 weeks prior to registration. Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible
  • No major surgical procedure within 28 days prior to registration or anticipation of need for a major surgical procedure during the course of the study
  • No administration of a live, attenuated vaccine within 30 days before registration 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
  • Patients who have received live attenuated vaccines within 30 days of the first dose of trial treatment are eligible at the discretion of the investigator. All seasonal influenza vaccines and vaccines intended to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19) are allowed

Exclusion Criteria:

  • Physicians should consider whether any of the following may render the patient inappropriate for this protocol:
  • Patients with life expectancy of less than 6 months
  • Psychiatric illness which would prevent the patient from giving informed consent
  • Medical conditions such as uncontrolled infection, uncontrolled diabetes mellitus or cardiac disease which, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient.
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
  • Patients with a "currently active" second malignancy other than non-melanoma skin cancers or cervical carcinoma in situ. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for >= 3 years.
  • Women and men of reproductive potential should agree to use an appropriate method of birth control throughout their participation in this study and for 5 months (150 days) after the last dose of study agent due to the teratogenic potential of the therapy utilized in this trial. Appropriate methods of birth control include abstinence, oral contraceptives, implantable hormonal contraceptives or double barrier method (diaphragm plus condom). 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.
  • A female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
  • REGISTRATION EXCLUSION
  • 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 prior to registration

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A Phase II/III Trial of Durvalumab and Chemotherapy for Patients With High Grade Upper Tract Urothelial Cancer Prior to Nephroureterectomy


Condition: Renal Pelvis and Ureter Urothelial Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04628767

Sponsor: National Cancer Institute (NCI)

Phase: Phase 2/Phase 3

Eligibility:

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

Inclusion Criteria:

  • STEP 1 REGISTRATION AND RANDOMIZATION
  • Patients must be >= 18 years of age
  • Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
  • Patient must have a diagnosis of high grade upper tract urothelial carcinoma proven by biopsy within 12 weeks (84 days) prior to registration/randomization with one of the following:
  • Upper urinary tract mass on cross-sectional imaging or
  • Tumor directly visualized during upper urinary tract endoscopy before referral to medical oncology
  • NOTE: Biopsy is standard of care (SOC) and required for enrollment to study. This is vital for best practice
  • Leukocytes >= 3,000/mcL (obtained =< 14 days prior to registration/randomization)
  • Platelets >= 100,000/mcL (obtained =< 14 days prior to registration/randomization)
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (or =< 2.5 x ULN for patients with Gilbert's disease) (obtained =< 14 days prior to registration/randomization)
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN (obtained =< 14 days prior to registration/randomization)
  • Hemoglobin (Hgb) >= 9 g/dL (obtained =< 14 days prior to registration/randomization)
  • NOTE: Packed red blood transfusion is allowed to achieve this parameter as per treating investigator
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration/randomization are eligible for this trial
  • NOTE: These patients must be stable on their anti-retroviral regimen with evidence of at least two undetectable viral loads within the past 6 months on the same regimen; the most recent undetectable viral load must be within the past 12 weeks. They must have a CD4 count of greater than 250 cells/mcL over the past 6 months on this same anti-retroviral regimen and must not have had a CD4 count < 200 cells/mcL over the past 2 years, unless it was deemed related to the cancer and/or chemotherapy induced bone marrow suppression. They must not be currently receiving prophylactic therapy for an opportunistic infection and must not have had an opportunistic infection within the past 6 months
  • NOTE: For patients who have received chemotherapy in the past 6 months, a CD4 count < 250 cells/mcL during chemotherapy is permitted as long as viral loads were undetectable during this same chemotherapy. They must have an undetectable viral load and a CD4 count >= 250 cells/mcL within 7 days of registration/randomization
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
  • NOTE: Testing for HIV, hepatitis B or hepatitis C is not required unless clinically indicated
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and have undetectable viral load. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
  • Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
  • Patient must have a body weight of > 30 kg
  • Patient must have life expectancy of >= 12 weeks
  • Patient must have creatinine clearance > 15 ml/min as by Crockroft-Gault formula or 24-hour creatinine clearance within 28 days prior to registration/randomization
  • NOTE: Patients will be assigned to cisplatin-ineligible and cisplatin-eligible cohorts based on their creatinine clearance, Eastern Cooperative Oncology Group (ECOG) performance status, and grade (if any) of peripheral neuropathy and/or hearing loss in keeping with SOC cisplatin contraindications. Patients that are cisplatin-eligible will be randomized to either Arm A or Arm B
  • Patients that meet any of the following criteria will be registered and assigned to the cisplatin-ineligible Arm C if they meet other eligibility criteria:
  • Creatinine clearance > 15 ml/min and =< 50 ml/min or hearing loss grade >= 3, or neuropathy >= 2, or ECOG PS 2
  • Patient must have an absolute neutrophil count (ANC) >= 1,000/mcL obtained =< 14 days prior to registration
  • Patient must have ECOG performance status 0-2
  • Patients that meet the following criteria will be randomized to the cisplatin-eligible Arm A or Arm B:
  • Patient must have creatinine clearance of > 50ml/min, PS ECOG 0-1, absence of hearing loss grade >= 3, and/or neuropathy >= 2
  • Patient must have an absolute neutrophil count (ANC) >= 1,500/mcL obtained =< 14 days prior to randomization
  • Patient must have left ventricular ejection fraction (LVEF) >= 50% by (either multigated acquisition scan [MUGA] or 2-D echocardiogram) obtained within obtained within 28 days prior to randomization

Exclusion Criteria:

  • Patients must not have any component of small cell/neuroendocrine carcinoma. Other variant histologic types are permitted provided the predominant (>= 50%) subtype is urothelial carcinoma
  • Patients must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All patients of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy. A patient of childbearing potential is defined as any patient, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
  • Patients of childbearing potential and sexually active patients must not expect to conceive or father children, either by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse from the time of registration, while on study treatment and for at least 6 months after the last dose of protocol treatment
  • Patients must have no evidence of metastatic disease or clinically enlarged regional lymph nodes (>= 1.5 cm short axis) on imaging required within 28 days prior to registration (Non-regional findings >=1.5 cm short axis that in the opinion of the investigator are not concerning for involvement based on radiographic characteristics, chronicity, avidity on positron emission tomography (PET) or other imaging or other criteria can be eligible based on investigator discretion).
  • NOTE: Patients with elevated alkaline phosphatase, calcium or suspicious bone pain/tenderness can also undergo baseline bone scans to evaluate for bone metastasis at the discretion of local provider.
  • Patient must meet below criteria for prior/current malignancy history:
  • Non-urothelial cancer malignancy history:
  • Patient must not have another active (or within two years) second malignancy other than resected non-melanoma skin cancers, resected in situ breast, cervical or other in situ carcinoma, and either clinically insignificant per the investigator (e.g. =< Gleason 3+4) on active surveillance (or watchful waiting) or previously treated prostate cancer with no rising prostate specific antigen (PSA) and no plan to treat
  • NOTE: Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Patients in whom concomitant or prior bladder/urethra predominant (>= 50%) urothelial carcinoma have been surgically resected and demonstrated to be only non-invasive cancer (< cT1N0) are eligible regardless of time elapsed
  • Urothelial cancer malignancy history:
  • Patient may have a history of resectable urothelial cancer as long as patients meet one of the following:
  • T0, Ta or Tis at any time
  • T1-4a N0 and no evidence of disease (NED) for more than 2 years from the latest therapy [e.g., radical surgery, transurethral resection of bladder tumor (TURBT), radiation, chemotherapy (neoadjuvant or adjuvant, or with radiation)]. Prior immune checkpoint inhibitor is not allowed.
  • Patient with history of >= pT4b, N+, and/or M1 is not eligible.
  • NOTE: Patients in whom concomitant or prior bladder/urethra predominant (>= 50%) urothelial carcinoma have been surgically resected and demonstrated to be only Ta or carcinoma in situ (CIS) (< cT1 N0) are eligible regardless of time elapsed
  • Patient must not have any uncontrolled illness including, but not limited to, ongoing or active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis [TB] testing in line with local practice), symptomatic congestive heart failure (CHF), myocardial infarction (MI) in last three months, or unstable angina pectoris, significant uncontrolled cardiac arrhythmia, clinically relevant liver cirrhosis, interstitial lung disease, or psychiatric illness/social situations that would limit compliance with study requirements
  • Patient must not have received prior radiation therapy to >= 25% of the bone marrow for other diseases
  • Patient must not have received prior systemic anthracycline therapy
  • NOTE: Patients who have received prior intravesical chemotherapy at any time for non-muscle invasive urothelial carcinoma of the bladder are eligible
  • Patient must not have either history of or active autoimmune disease requiring immunosuppressive therapy within 2 years prior to registration/randomization or any history of inflammatory bowel disease (inflammatory bowel disease [IBD], colitis, or Crohn's disease), neuromuscular autoimmune condition, immune-related pneumonitis or interstitial lung disease. Patients with well-controlled hyper/hypothyroidism, celiac controlled by diet alone, diabetes mellitus type I, vitiligo, alopecia, psoriasis, eczema, lichen planus, or similar skin/mucosa condition are eligible
  • Patient must not be on or have used immunosuppressive medication within 14 days prior to the first dose of durvalumab. The following are exceptions to this criterion:
  • Intranasal, inhaled, intra-auricular, topical steroids, or local steroid injections (e.g. intra-articular injection
  • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent at the time of enrollment
  • Steroids as premedications for hypersensitivity reactions (e.g. computed tomography [CT] scan premedication)
  • Patient must not have received live attenuated vaccine within 30 days prior to the first dose of durvalumab, while on protocol treatment and within 30 days after the last dose of durvalumab
  • Patient must not have had a major surgical procedure within 28 days prior to registration/randomization
  • NOTE: Cystoscopy/ureteroscopy, stent placement or nephrostomy tube is not considered major surgery
  • Patient must not have history of allogenic organ transplantation

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Phase II Trial of Intravesical Gemcitabine and MK-3475 (Pembrolizumab) in the Treatment of Patients With BCG-Unresponsive Non-Muscle Invasive Bladder Cancer


Condition: Bladder Urothelial Carcinoma In Situ, Invasive Bladder Mixed Carcinoma, Stage 0a Bladder Cancer AJCC v8, Stage 0is Bladder Cancer AJCC v8, Stage I Bladder Cancer AJCC v8

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04164082

Sponsor: National Cancer Institute (NCI)

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • High grade Ta, T1 or CIS urothelial carcinoma. Accrual of patients with Ta or T1 disease may be closed to ensure adequate patients enrollment to meet the primary endpoint
  • Persistent disease (defined as not achieving disease free status) after completing therapy with at least induction BCG (>= 5 doses) and the first round of maintenance or second induction course (>= 2 doses). The subsequent round of BCG, either maintenance or repeat induction, must be given within 6 months of initial induction BCG.
  • Persistent high risk NMIBC (T1, high grade Ta and/or CIS) must be within 9 months of the last BCG instillation despite having received adequate BCG as defined above.
  • Registration must be within 12 months of last BCG instillation
  • High grade T1 after completing therapy with at least induction BCG (>= 5 doses) or after completing therapy with at least induction BCG (>= 5 doses) and first round of maintenance or second induction course (>= 2 doses). The subsequent round of BCG, either maintenance or repeat induction, must be given within 6 months of initial induction BCG
  • Disease recurrence (T1) must be within 9 months of the last BCG instillation despite having received adequate BCG as defined above
  • Registration must be within 12 months of last BCG instillation
  • Patients who are disease free at 6 months after starting BCG but have high grade recurrence (T1, Ta, CIS) while on maintenance therapy would be eligible
  • The recurrence must be within 6 months of the last BCG dose.
  • Registration must be within 12 months of last maintenance BCG instillation
  • Patients must be deemed unfit for radical cystectomy by the treating physician or refuse radical cystectomy
  • All patients must have histologically confirmed urothelial cancer of the bladder within 60 days prior to registration
  • All visible tumor must be completely resected 60 days prior to registration (residual pure CIS is permitted)
  • All patients must have had a cystoscopy (or transurethral resection of bladder tumor [TURBT] with complete resection) without papillary tumor and negative urinary cytology within 28 days of registration. (positive cytology is allowed in patients with CIS)
  • All patients with T1 tumors must undergo a re-staging TURBT within 60 days of registration. There must be uninvolved muscularis propria present in the re-staging TURBT. The initial TURBT prior to re-staging TURBT may be greater than 60 days prior to registration
  • Patients must have had imaging with computed tomography (CT) or magnetic resonance imaging (MRI) abdomen/pelvis within 90 days of registration demonstrating no evidence of metastasis.
  • Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects
  • Women and men of reproductive potential should agree to use an appropriate method of birth control throughout their participation in this study due to the teratogenic potential of the therapy utilized in this trial. Include as applicable: Appropriate methods of birth control include abstinence, oral contraceptives, implantable hormonal contraceptives or double barrier method (diaphragm plus condom)
  • A woman of childbearing potential (WOCBP) must not have a positive urine pregnancy test within 7 days prior to registration. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Patients must not be pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with registration through the last dose of treatment
  • Age >= 18 years
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Absolute neutrophil count (ANC) >= 1,500/mm^3
  • Platelet count >= 100,000/mm^3
  • Hemoglobin >= 9.0 g/dL
  • Creatinine =< 1.5 x upper limit of normal (ULN)
  • In patients with creatinine > 1.5 x ULN, if measured or calculated creatinine clearance > 30 mL/min, then patient is eligible
  • Total bilirubin =< 1.5 x ULN
  • In patients with a total bilirubin > 1.5 x ULN, if direct bilirubin < 1.0 X ULN, then patient is eligible
  • Aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) =< 2.5 x ULN
  • Patients with human immunodeficiency virus (HIV) are eligible with the following:
  • On effective anti-retroviral therapy with undetectable viral load within 6 months of registration

Exclusion Criteria:

  • Mixed variant histology (adenocarcinoma, squamous cell carcinoma) is eligible, but pure variant histology is ineligible.
  • Patients cannot have had a history of urothelial carcinoma in the ureters or prostatic urethra 24 months prior to registration
  • Patients must not be currently participating in or have participated in a study of an investigational agent or have used an investigational device within 4 weeks prior to study registration
  • Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been more than 4 weeks after the last dose of the previous investigational agent at time of registration
  • Patients must not have prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137)
  • Patients must not have undergone prior allogeneic hematopoietic stem cell transplantation within the last 5 years prior to registration. (Participants who have had a transplant greater than 5 years ago are eligible as long as there are no symptoms of graft versus host disease [GVHD])
  • Patients must not have received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to treatment
  • Note: Participants must have recovered from all adverse events (AEs) due to previous therapies to =< grade 1 or baseline. Participants with =< grade 2 neuropathy may be eligible
  • Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment
  • Patients must not have received prior radiotherapy within 2 weeks of study registration. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis
  • Patients must not have received radiation therapy to the lung that is > 30 Gy within 6 months prior to trial registration
  • Patients must not have had an active autoimmune disease requiring systemic treatment within 24 months prior to registration. Autoimmune diseases include, but not limited to, lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis
  • Patients must not have a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to registration
  • Note: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed
  • Patients must not have a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study
  • Patients must not have active tuberculosis
  • Patients must not have been treated with antibiotics for an active infection within 14 days prior to registration. Prophylactic antibiotics are permitted. Treatment for a urinary tract infection (UTI) is allowed but must be deemed adequately treated by the treating physician prior the start of cycle 1 (C1) day 1 (D1)
  • Patients must not have a history of idiopathic pulmonary fibrosis or organizing pneumonia
  • Patients must not have a history of (non-infectious) pneumonitis that required steroids or have current pneumonitis
  • HIV-infected participants must not have a history of Kaposi sarcoma and/or multicentric Castleman disease
  • Patients must not have a known additional malignancy that has had progression or has required active treatment in the last three years. Exceptions include basal or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. A history of prostate cancer that was treated with definitive intent is allowed, provided that the prostate-specific antigen (PSA) is undetectable for at least 1 year while off androgen deprivation therapy
  • Patients must not have known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment
  • Patients must not have severe hypersensitivity (>= grade 3) to pembrolizumab and/or any of its excipients
  • Patients must not have an active infection requiring systemic therapy
  • Patients must not have a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (defined as hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected) infection
  • Note: No testing for hepatitis B and hepatitis C is required unless mandated by a local health authority
  • Patients must not have received live vaccines within 30 days of study drug administration. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed. COVID-19 vaccinations are permitted.
  • Physicians should consider whether any of the following may render the patient inappropriate for this protocol:
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator

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Multicenter Phase 3 Pivotal Study to Evaluate the Safety and Efficacy of TOOKAD (Padeliporfin) Vascular Targeted Photodynamic Therapy in the Treatment of Low Grade Upper Tract Urothelial Cancer


Condition: Transitional Cell Cancer of Renal Pelvis and Ureter

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04620239

Sponsor: Steba Biotech S.A.

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

  • Male and female patients 18 years or older
  • Able to understand and provide written informed consent and willing to comply with all tests and procedures associated with the study
  • New or recurrent low-grade, non-invasive UTUC disease
  • Biopsy-proven disease . A concurrence of the central pathology reader will be required for eligibility.
  • Up to 2 biopsy-proven sites of low-grade involvement with the largest tumor (index tumor) between 5 mm and 15 mm in diameter (as measured by endoscopy), both located in the calyces,renal pelvis or in the ureter of the ipsilateral kidney, with an absence of high-grade cells on cytology. (Ureter involvement should be in one anatomical location with no more than 20 mm of contiguous ureteral length)
  • Karnofsky Performance Status ≥ 50%
  • Adequate organ function defined at baseline as:
  • ANC ≥1,000/ μl,
  • Platelets ≥75,000/ μl, Hb ≥9 g/dl,
  • INR ≤ 2
  • Estimated glomerular giltration rate (eGFR) ≥30 ml/min (using CKD-EPI Method)
  • Total serum bilirubin <3 mg/dL, AST/ALT ≤5× upper limit of normal

Exclusion Criteria:

  • Current high-grade or muscle invasive (>pT1) urothelial carcinoma of the bladder
  • Carcinoma in situ (CIS) current or previous in the upper urinary tract
  • History of invasive T2 or higher urothelial cancer in past 2 years
  • Participation in another clinical study involving an investigational product within 1 month before study entry
  • BCG or local chemotherapy treatment (including VEGF-targeted therapy) in the upper urinary tract within 2 months prior to inclusion
  • Systemic chemotherapy treatment (including VEGF-targeted therapy) within 2 months prior to enrollment
  • Prohibited medication that could not be adjusted or discontinued prior to study treatment • Patients with photosensitive skin diseases or porphyria
  • Any other medical or psychiatric co-morbidities, including decompensated heart failure, unstable angina or coronary artery disease or severe pulmonary or liver disease or current heavy smoker that, in the opinion of the study investigator, would make the patient a poor candidate for the study
  • Pregnant or breast-feeding women.Women of childbearing potential (WOCBP) must undergo a negative serum pregnancy test prior to study entry.
  • Men and women of reproductive potential not willing to observe conventional and effective birth control for the duration of treatment and for 90 days following the last padeliporfin VTP treatment.

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Treatment Of Metastatic Bladder Cancer at the Time Of Biochemical reLApse Following Radical Cystectomy


Condition: Bladder Cancer, Bladder Cancer, Metastatic

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04138628

Sponsor: Jørgen Bjerggaard Jensen

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • ≥18 years of age at the time of signing the Informed Consent Form
  • For male study subjects: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm.
  • Signed Informed Consent Form
  • ECOG PS 0, 1 or 2
  • Is, according to the Investigator's judgement, able to comply with the trial protocol
  • Ability to understand the Participant Information Sheet orally and in writing
  • Preoperative PET/CT of thorax, abdomen, and pelvis with no suspicion of organ metastases or lymph node metastasis* above the aortic bifuraction
  • Study Subjects undergoing radical cystectomy due to histologically documented muscle invasive urothelial carcinoma (including subtypes) stage cT2-4a in the urinary bladder following NAC** in cisplatin-fit Study Subjects.
  • Study Subjects who have undergone down-staging chemotherapy because of lymph node metastasis with no organ metastases can be included if complete response regarding lymph nodes are identified on preoperative imaging.
  • NAC includes Study Subjects who have stopped after one course of chemotherapy because of side effects or local non-metastatic progression

Exclusion Criteria:

  • Subjects undergoing non-radical cystectomy for palliative reasons
  • Non-radical surgery estimated intraoperative
  • Other histology of BC than urothelial carcinoma
  • mixed tumours with urothelial features are allowed
  • Concomitant invasive cancer within 5 years other than non-melanoma skin cancer and prostate cancer without metastasis
  • Known contraindication to immunotherapy
  • A history of autoimmune disease. Study Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
  • Study Subjects who meet any of the following criteria will be excluded from study entry:
  • History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
  • Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) within 4 weeks or 5 drug elimination half-lives (whichever is longer) prior to initiation of study treatment
  • HIV positive
  • History of pneumonitis (History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
  • Hepatitis B or hepatitis C infection
  • Subjects who have received a live, attenuated vaccine within 28 days prior to enrolment

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An Open-label, Randomized, Controlled Phase 3 Study of Enfortumab Vedotin in Combination With Pembrolizumab Versus Chemotherapy Alone in Previously Untreated Locally Advanced or Metastatic Urothelial Cancer


Condition: Urothelial Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04223856

Sponsor: Astellas Pharma Global Development, Inc.

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

  • Histologically documented, unresectable locally advanced or metastatic urothelial carcinoma
  • Measurable disease by investigator assessment according to RECIST v1.1
  • Participants with prior definitive radiation therapy must have measurable disease per RECIST v1.1 that is outside the radiation field or has demonstrated unequivocal progression since completion of radiation therapy
  • Participants must not have received prior systemic therapy for locally advanced or metastatic urothelial carcinoma with the following exceptions:
  • Participants that received neoadjuvant chemotherapy with recurrence >12 months from completion of therapy are permitted
  • Participants that received adjuvant chemotherapy following cystectomy with recurrence >12 months from completion of therapy are permitted
  • Must be considered eligible to receive cisplatin- or carboplatin-containing chemotherapy, in the investigator's judgment
  • Archival tumor tissue comprising muscle-invasive urothelial carcinoma or a biopsy of metastatic urothelial carcinoma must be provided for PD-L1 testing prior to randomization
  • Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1, or 2
  • Adequate hematologic and organ function

Exclusion Criteria:

  • Previously received enfortumab vedotin or other monomethyl auristatin E (MMAE)-based antibody-drug conjugate (ADCs)
  • Received prior treatment with a programmed cell death ligand-1 (PD-(L)-1) inhibitor for any malignancy, including earlier stage urothelial cancer (UC), defined as a PD-1 inhibitor or PD-L1 inhibitor
  • Received prior treatment with an agent directed to another stimulatory or co inhibitory T-cell receptor
  • Received anti-cancer treatment with chemotherapy, biologics, or investigational agents not otherwise prohibited by exclusion criterion 1-3 that is not completed 4 weeks prior to first dose of study treatment
  • Uncontrolled diabetes
  • Estimated life expectancy of less than 12 weeks
  • Active central nervous system (CNS) metastases
  • Ongoing clinically significant toxicity associated with prior treatment that has not resolved to ≤ Grade 1 or returned to baseline
  • Currently receiving systemic antimicrobial treatment for active infection (viral, bacterial, or fungal) at the time of randomization. Routine antimicrobial prophylaxis is permitted.
  • Known active hepatitis B, active hepatitis C, or human immunodeficiency virus (HIV) infection.
  • History of another invasive malignancy within 3 years before the first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy
  • Documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms consistent with New York Heart Association (NYHA) Class IV within 6 months prior to randomization
  • Receipt of radiotherapy within 2 weeks prior to randomization
  • Received major surgery (defined as requiring general anesthesia and >24 hour inpatient hospitalization) within 4 weeks prior to randomization
  • Known severe (≥ Grade 3) hypersensitivity to any enfortumab vedotin excipient contained in the drug formulation of enfortumab vedotin
  • Active keratitis or corneal ulcerations
  • History of autoimmune disease that has required systemic treatment in the past 2 years
  • History of idiopathic pulmonary fibrosis, organizing pneumonia, drug induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
  • Prior allogeneic stem cell or solid organ transplant
  • Received a live attenuated vaccine within 30 days prior to randomization

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A Phase 3, Randomized, Double-blind, Placebo-controlled Clinical Trial to Study the Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Chemoradiotherapy (CRT) Versus CRT Alone in Participants With Muscle-invasive Bladder Cancer (MIBC) (KEYNOTE-992)


Condition: Urinary Bladder Neoplasms

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04241185

Sponsor: Merck Sharp & Dohme LLC

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

  • Has a histologically confirmed initial diagnosis of muscle-invasive bladder cancer (MIBC) with predominant urothelial histology
  • Has clinically nonmetastatic bladder cancer (N0M0)
  • Has planned and is eligible to receive chemoradiotherapy (CRT) and one of the protocol-specified radiosensitizing chemotherapy regimens
  • Has Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
  • Demonstrates adequate organ function
  • Male participants are eligible to participate if they agree to the following during the intervention period and for at least 90 days after the last dose of CRT treatment:
  • Refrain from donating sperm
  • Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent; or must agree to use contraception unless confirmed to be azoospermic
  • A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
  • Is not a woman of childbearing potential (WOCBP)
  • Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the intervention period and for at least 180 days the time needed to eliminate each study intervention after the last dose of study intervention; and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period. The length of time required to continue contraception for each study intervention is as follows: MK-3475
  • 120 days and CRT
  • 180 days

Exclusion Criteria:

  • Has the presence of diffuse carcinoma in situ (CIS) (multiple foci of CIS) throughout the bladder
  • Has the presence of urothelial carcinoma (UC) at any site outside of the urinary bladder in the previous 2 years except for Ta stage/T1 stage/CIS of the upper tract if the participant has undergone a complete nephroureterectomy
  • Has a known additional malignancy that is progressing or has required active therapy within the past 3 years, except basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer or other carcinoma in situ that has undergone potentially curative therapy
  • Has the presence of bilateral hydronephrosis
  • Has limited bladder function with frequency of small amounts of urine (< 30 mL), urinary incontinence, or requires self-catheterization or a permanent indwelling catheter
  • Has received prior pelvic/local radiation therapy or any antineoplastic treatment for muscle-invasive bladder cancer (MIBC). Treatment for non-muscle invasive bladder cancer (NMIBC) with intravesical instillation therapy that was completed ≥28 days prior to randomization is allowed. Prior systemic treatment of NMIBC is not permitted.
  • Received prior therapy with an anti-PD-1 (programmed cell death protein 1), anti-PD-L1 (programmed death-ligand 1), or anti-PD-L2 (programmed cell death 1 ligand 2), or with an agent directed to another stimulatory or coinhibitory T-cell receptor (e.g., CTLA-4 [cytotoxic T-lymphocyte-associated protein 4], OX 40, or CD137 [cluster of differentiation 137])
  • Has received a live vaccine within 30 days before the first dose of study medication
  • Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study medication
  • Has known severe hypersensitivity (≥Grade 3) to the selected chemotherapy regimen, and/or any of their excipients and excipients of pembrolizumab
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days before the first dose of study medication
  • Has an active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed
  • Has a history of non-infectious pneumonitis that required steroids or has current pneumonitis
  • Has an active infection requiring systemic therapy
  • Has a known history of human immunodeficiency virus (HIV) infection
  • Has a known history of hepatitis B or known active hepatitis C virus infection
  • Has a known history of active tuberculosis (TB; Bacillus tuberculosis)
  • Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study
  • Has had an allogenic tissue/solid organ transplant

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Bladder Cancer Longitudinal Biorepository for Development of Novel Therapeutics/Biomarkers


Condition: Bladder Cancer

Study Type: Observational [Patient Registry]

Clinical Trials Identifier NCT 8-digits: NCT03413982

Sponsor: University of Kansas Medical Center

Phase:

Eligibility:

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

Inclusion Criteria:

  • Patients who present to clinic with presumed bladder cancer or have a diagnosis of bladder cancer are eligible to participate
  • Patients can participate in any additional research studies during the patients' participation within this protocol.

Exclusion Criteria:

  • Patients who do not have presumed bladder cancer will not be eligible

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Randomized Clinical Trial of Intracorporeal vs Extracorporeal Urinary Diversion After Robot Assisted Radical Cystectomy


Condition: Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03469362

Sponsor: University of Miami

Eligibility:

  • Age: minimum 18 Years maximum 99 Years
  • Gender: All

Inclusion Criteria:

  • Biopsy-proven urothelial cancer being considered for RARC.
  • Clinical stage T1-T4, N0-1, M0 or refractory carcinoma in situ.
  • Subject must be already scheduled to have a RARC at the discretion of the surgeon and with the patient's agreement.

Exclusion Criteria:

  • Inability to give informed consent
  • Prior major abdominal and pelvic open surgical procedures that would preclude a safe robotic approach, as determined by the treating surgeon.
  • At the discretion of the treating surgeon, any pre-existing condition such as severe chronic obstructive pulmonary disease that precludes a safe initiation or maintenance of pneumoperitoneum over a prolonged period of time and during surgery.
  • Age <18 or >99 years.

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SArcopenia, Mobility, PHYsical Activity and Post-operative Risk of Bladder Carcinoma in the Elderly


Condition: Sarcopenia, Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03362801

Sponsor: University Hospital, Caen

Eligibility:

  • Age: minimum 65 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • confirmed urothelial bladder carcinoma ( RTUV)
  • indication of radical cystectomy
  • Able, informed and with informed consent for the study
  • affiliated to the social security system
  • talking French

Exclusion Criteria:

  • Life expectancy <6 months
  • other active malignant tumors or other severe concomitant chronic pathologies affecting the general condition of the patient and / or likely to limit compliance with the requirements of the study.
  • treatments incompatible with the study: previous corticosteroid treatment prolonged for more than one month (induces iatrogenic sarcopenia).

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Adjuvant Radiotherapy in Patients With Pathological High-risk Bladder Cancer: A Randomized Multicentre Phase II Study


Condition: Patients With High-risk MIBC

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03333356

Sponsor: UNICANCER

Eligibility:

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

Inclusion Criteria:

  1. To be eligible, the patients must fulfil all of the following inclusion criteria:
  2. Patients with histologically-confirmed muscle-invasive bladder cancer, either with pure urothelial carcinomas, or dominant urothelial carcinomas (>50%) combined with other histological variants including: micropapillary, epidermoid, or adenocarcinomas, are eligible. Patients with small cell variants, pure adenocarcinomas, or pure epidermoid carcinomas are not eligible.
  3. Patients with radical cystectomy and pelvic lymph nodes dissection with no microscopic residual disease (R0 and R1). Note that only R1 patients without urinary diversion as orthotropic neo-bladder replacement are eligible for the study, to limit cystectomy bed radiation induced toxicities.
  4. Patients with tumours of TNM staging: pN0-2, M0 by imagery, and pT3a, pT3b, pT4a, and pT4b, as well as, pTX-pN1-2, pTX-NX-R1 are eligible.
  5. Patients having received neo-adjuvant or adjuvant chemotherapy treatment are eligible. Randomization is allowed only if AE due to chemotherapy are ≤grade 2 at randomization.
  6. Patients ≥18 years old.
  7. Eastern Cooperative Oncology Group (ECOG) performance status ≤
  8. Absolute neutrophil count (ANC) ≥1500 cells/mm³.
  9. Platelets ≥100000 cells/mm³.
  10. Haemoglobin ≥8 g/dL (Note: following a blood transfusion or another intervention if required).
  11. Adequate hepatic function: aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) ≤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.
  12. Adequate renal function: clearance >30 mL/min (MDRD).
  13. Patients having provided written informed consent prior to any study-related procedures.
  14. Patients affiliated to the social security scheme.
  15. Patients willing and able to comply with the scheduled visits, treatment plan, laboratory tests, and other study procedures indicated in the protocol.

Exclusion Criteria:

  • Patient must not be enrolled if he/she fulfils any of the following non-inclusion criteria: 1. Patients with R1 resection and with orthotropic neo-bladder reconstruction as urinary diversion are not eligible. 2. Patients with clinical or radiological evidence of metastases or N3 staged bladder cancer are not eligible. 3. Prior invasive solid tumours or haematological malignancies unless disease free for a minimum of 3 years prior to randomisation except:
  • skin basal cell carcinoma,
  • in situ epithelioma of the cervix,
  • or prostate cancer: incidentally discovered during cystoprostatectomy and pelvic lymph node dissection and with a good prognosis (T stage
  • Unstable angina or congestive heart failure that required hospitalization in the 6 months before randomisation.
  • Transmural myocardial infarction in the 6 months prior to randomisation.
  • Acute bacterial or fungal infection requiring intravenous antibiotics at randomisation.
  • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of randomisation.
  • Severe hepatic disease: Child-Pugh Class B or C hepatic disease.
  • Known acquired immune deficiency syndrome (AIDS); the study treatment could impact blood count. 9. Patients with any other disease or illness which requires hospitalization or is incompatible with the study treatment are not eligible. 10. 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. 11. Patients enrolled in another therapeutic study within 30 days prior of randomisation. 12. Person deprived of their liberty or under protective custody or guardianship.

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Influence of Hormone Treatment in Radiation Therapy for Bladder Cancer


Condition: Bladder Cancer, Radiation Therapy Complication, Quality of Life

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT04282876

Sponsor: Aarhus University Hospital

Phase:

Eligibility:

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

Inclusion Criteria:

  • T2-T4 bladder cancer
  • radiation therapy
  • able to fill out questionnaires
  • signed informed consent

Exclusion Criteria:

  • KAD prior to TUR-B
  • dementia or other cognitive impairment
  • metastatic disease

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A Phase 2 Study of Avelumab in Combination With Bladder-Directed Radiation in Cisplatin-Ineligible Patients With Muscle-Invasive Urothelial Carcinoma of the Bladder


Condition: Bladder Cancer, Muscle Invasive Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03747419

Sponsor: Dana-Farber Cancer Institute

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • to participate in the study. Inclusion Criteria:
  • Histologically confirmed transitional cell (urothelial) carcinoma of the bladder that is invasive into the muscularis propria (≥T2 disease) within 6 months of enrollment date. The presence of variant histologies (squamous, adenocarcinoma, micropapillary, etc.) is allowed. Note: A prior diagnosis of non-muscle-invasive bladder cancer (≤T1) managed with transurethral resection with or without intravesicular therapy (now with muscle invasion) is allowed.
  • Inability to receive cisplatin-based chemotherapy, as defined by creatinine clearance <60 ml/min, ECOG PS ≤2, grade 2 or higher hearing loss, NYHA class 3 or higher, neuropathy (grade 2 or higher), or patient refusal to receive cisplatin-based chemotherapy. Additional Inclusion Criteria:
  • Male or female subjects aged ≥18 years
  • ECOG performance status ≤2 or Karnofsky score ≥60% (see Appendix A)
  • Life expectancy of greater than 1 year
  • Demonstrate normal organ and marrow function
  • Estimated creatinine clearance > 30 mL/min according to the Cockcroft-Gault formula.
  • Women of child-bearing age must have a negative serum pregnancy test at screening.
  • Women of child-bearing potential and men must agree to use a highly effective method of contraception (hormonal or barrier method of birth control, or abstinence) beginning prior to study entry, for the duration of study participation, and for at least 30 days after last avelumab treatment administration if the risk of conception exists
  • Ability to start study treatment (first cycle of Avelumab) within 1-8 weeks of the most recent pre-study TURBT.
  • Ability to understand and willingness to sign a written informed consent document Exclusion Criteria:
  • Prior intravenous therapy for treatment of bladder cancer
  • Prior pelvic radiation
  • Any component of small cell histology in the bladder biopsy
  • Any concurrent chemotherapy, biologic, or hormonal therapy for cancer treatment
  • Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroid, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) are allowed.
  • History of another malignancy within 5 years prior to randomization except for: non-muscle-invasive bladder cancer (i.e., ≤T1), completely resected basal cell or squamous cell skin cancer, completed resected carcinoma-in-situ of any site, or localized prostate cancer managed definitively with a non-radiation based approach. Additional

Exclusion Criteria:

  • Prior intravenous therapy for treatment of bladder cancer
  • Prior pelvic radiation
  • Any component of small cell histology in the bladder biopsy
  • Any concurrent chemotherapy, biologic, or hormonal therapy for cancer treatment
  • Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroid, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) are allowed.
  • History of another malignancy within 5 years prior to randomization except for: non-muscle-invasive bladder cancer (i.e., ≤T1), completely resected basal cell or squamous cell skin cancer, completed resected carcinoma-in-situ of any site, or localized prostate cancer managed definitively with a non-radiation based approach. Additional Exclusion Criteria:
  • Evidence of lymph node involvement or metastatic disease on CT of the chest, abdomen, and pelvis. To be considered positive, a lymph node must measure >15 mm in short axis.
  • Clinically significant (i.e. active) cardiovascular disease: symptomatic congestive heart failure (≥ New York Heart Association Classification Class II), unstable angina pectoris, serious cardiac arrhythmia requiring medication, or CVA/stroke/MI (< 6 months prior to enrollment)
  • Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade ≥ 3)
  • Breast feeding women who are unwilling to stop breastfeeding during treatment and for at least one month after the duration of treatment
  • Patients with known history of testing positive for HIV or known acquired immunodeficiency syndrome
  • Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.
  • Active infection requiring intravenous antibiotic therapy
  • Vaccination within 4 weeks of the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines
  • Major surgery within the last 30 days (with the exception of TURBT).
  • Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive)
  • Prior organ transplantation including allogenic stem-cell transplantation
  • Patient is unwilling to stop (or wishes to start) taking herbal and natural remedies that may have immune-modulating effects during the study period
  • Persisting toxicity related to prior therapy (NCI CTCAE v. 4.03 Grade > 1); however, alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on investigator's judgment are acceptable
  • Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
  • Pregnant women are excluded from this study.

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A Phase II Study of TAS-102 in Metastatic Platinum and Checkpoint Inhibitor-resistant Bladder Cancer


Condition: Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03762161

Sponsor: Rahul Parikh

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • Ability of participant to understand this study, and participant willingness to sign a written informed consent.
  • Participants must have histologically or cytologically confirmed locally advanced unresectable or metastatic urinary bladder (urothelial) cancer. Participants with mixed histologies are permitted as long as transitional cell carcinoma is present in the pathological specimen.
  • Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension
  • Documented progression on or within 12 months of treatment with one previous platinum-containing regimen or ineligible to receive platinum-containing regimen. Neo-adjuvant or adjuvant platinum-based chemotherapy will be deemed to be first-line when participants progressed within 12 months of the last dose
  • Documented progression on prior checkpoint inhibitor or ineligible to receive check-point inhibitor
  • Adequate performance status, organ, and marrow function.
  • Women of child-bearing potential and men with partners of child-bearing potential must agree to practice sexual abstinence, or to use two forms of adequate contraception.
  • Men of child-bearing potential must not father a child or donate sperm while on this study and for 6 months after their last study treatment

Exclusion Criteria:

  • Patients who have had chemotherapy or radiotherapy within 4 weeks of enrollment/registration.
  • Current or anticipated use of other investigational agents while participating in this study.
  • Psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant or breast feeding (if applicable).
  • Patients with known brain metastases
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to TAS 102.
  • Patients with HIV on anti-retro-viral therapy with thymidine kinase substrates, for example, stavudine, zidovudine, telbivudine.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia. Undergoing active treatment for a co-existing malignancy with the exception of adequately treated basal cell carcinoma, squamous cell skin cancer, thyroid cancer or incidental prostate adenocarcinoma detected at radical cystectomy

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Ex-Vivo Trial of En-bloc Transurethral Resection of Bladder Tumor (En-bloc TURBT) Specimens Using a Redesigned Surgical Resectoscope Device


Condition: Bladder Cancer

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT04235764

Sponsor: National Cancer Institute (NCI)

Phase:

Eligibility:

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

Inclusion Criteria:

  • Patients requiring surgical removal of the bladder at the NIH Clinical Center. NOTE: Reasons for need for surgical removal of bladder include cancer or benign condition for which a surgeon determined surgical removal of the bladder is recommended. Patient's with invasive bladder cancer requiring cystectomy are eligible for enrollment. Bladder cancer remains the most common reason for cystectomy. Patients with clinical advanced disease and having other treatments/or participating in other trials remain eligible for enrollment in this study.
  • Men and women
  • Age greater than or less than 18 years
  • Deemed clinically appropriate for the planned surgical procedure.
  • Ability of subject to understand and the willingness to sign a written informed consent document.
  • Subjects will be asked to co-enroll in 15-C-0087, "Care of the Urothelial Cancer Patient and Prospective Collection of Biospecimens from Healthy Volunteers and Urothelial Cancer Patients." NOTE: Most participants are expected to already be enrolled in 15-C-0087 prior to entry in this study.

Exclusion Criteria:

  • Cystectomy during pregnancy would subject the fetus to significant risk of miscarriage or premature labor. For this reason, pregnant women are ineligible for this study.

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