Summary

for people ages 18 years and up (full criteria)
at Sacramento, California and other locations
study started
estimated completion

Description

Summary

This phase II trial studies how well gemcitabine hydrochloride and cisplatin work in treating participants with invasive bladder urothelial cancer. Drugs used in chemotherapy, such as gemcitabine hydrochloride and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Official Title

A Phase II Study of Dose-Dense Gemcitabine Plus Cisplatin (ddGC) in Patients With Muscle-Invasive Bladder Cancer With Bladder Preservation for Those Patients Whose Tumors Harbor Deleterious DNA Damage Response (DDR) Gene Alterations

Details

PRIMARY OBJECTIVES:

  1. To determine the 3-year event free survival, defined as the proportion of patients without invasive or metastatic recurrence following definitive dose dense gemcitabine hydrochloride (gemcitabine) and cisplatin chemotherapy in those patients whose pre-treatment transurethral resection of bladder tumor (TURBT) tumors harbor deleterious DDR gene alterations and who achieve < cT1 response to chemotherapy.

SECONDARY OBJECTIVES:

  1. To determine the clinical response rate (< cT1) for patients harboring deleterious DDR gene alterations following dose dense gemcitabine and cisplatin.

II. To determine the bladder-intact and overall survival for DDR-altered patients with < cT1.

III. For DDR gene altered patients who elect radical cystectomy despite < cT1, to determine the pT0 rate in this patient population.

IV. To determine the pathologic response rate at cystectomy and 3-year recurrence-free and overall survival for patients without DDR mutations who are registered onto this trial.

  1. To assess the local treatment burden (Bacillus Calmette-Guerin [BCG] therapy, resection of non-invasive disease) over time in the bladder-sparing group.

OUTLINE:

Participants receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on day 1, cisplatin IV on days 1 and 2, and pegfilgrastim subcutaneously (SC) on day 3. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unaccepted toxicity. Participants are then assigned to 1 of 2 arms.

ARM I: Participants with DDR gene alteration and disease stage < cT1 undergo bladder sparing.

ARM II: Participants with DDR gene alteration and disease stage >= cT1 or participants without DDR gene alteration undergo radical cystectomy or chemoradiotherapy.

After completion of study treatment, participants are followed up for 5 years.

Keywords

Infiltrating Bladder Urothelial Carcinoma Stage II Bladder Urothelial Carcinoma Stage III Bladder Urothelial Carcinoma Carcinoma Carcinoma, Transitional Cell Cisplatin Gemcitabine Gemcitabine Hydrochloride Pegfilgrastim Radical Cystectomy Chemoradiotherapy

Eligibility

For people ages 18 years and up

Inclusion Criteria:

  • Step 1 Patient Registration Eligibility Criteria
  • Histologically confirmed muscle-invasive urothelial carcinoma of the bladder. Urothelial carcinoma invading into the prostatic stroma with no histologic muscle invasion is allowed, provided the extent of disease is confirmed via imaging and/or examination under anesthesia (EUA). The diagnostic TURBT sample must have been obtained within 60 days prior to registration
  • 20 unstained slides (10 micron thickness) of formalin-fixed paraffin-embedded (FFPE) pre-treatment diagnostic transurethral resection (TUR) specimen available (for sequencing), with 2 (5 micron) slides at the start and end of the 20 slides, for a total of 22 unstained slides. An FFPE block is also acceptable
  • Clinical stage T2-T4aN0/xM0 disease
  • Medically appropriate candidate for radical cystectomy as assessed by surgeon
  • No concomitant multifocal carcinoma in situ; a single focus is allowed
  • One focus of muscle-invasive bladder cancer and/or a tumor < 5 cm in size
  • No clinical or radiographic evidence for locally advanced or metastatic disease
  • No prior anti-PD-1, anti PD-L1 therapies, or systemic chemotherapy (prior intravesical induction immunotherapy for non-muscle invasive disease is allowed, defined as BCG x 6 treatments; BCG refractory disease, defined as disease recurrence within 3 months of BCG therapy, is not allowed)
  • No prior radiation therapy to the bladder
  • No major surgery or radiation therapy =< 4 weeks of registration
  • Not pregnant and not nursing. This study involves an agent that has known genotoxic, mutagenic and teratogenic effects. For women of childbearing potential only, a negative pregnancy test done =< 14 days prior to registration is required
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Absolute neutrophil count (ANC) >= 1,000/mm3

  • Platelet count >= 100,000/mm3

  • Calculated creatinine clearance >= 55 mL/min
  • Total bilirubin =< 1.5 x upper limit of normal (ULN)
  • (For patients with documented Gilbert's syndrome bilirubin =< 3 x ULN)
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN
  • Alkaline phosphatase =< 2.5 x ULN
  • No hydronephrosis refractory to urinary diversion
  • No evidence of New York Heart Association (NYHA) functional class III or IV heart disease
  • No ongoing cardiac dysrhythmias of National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade >= 2
  • No pre-existing sensory grade >= 2 neuropathy
  • No pre-existing grade >= 2 hearing loss
  • No serious intercurrent medical or psychiatric illness, including serious active infection
  • None of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, or transient ischemic attack
  • No known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness or other active infection. HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with the drugs used in this trial. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy, when indicated
  • No history of allergic reaction attributed to compounds of similar chemical or biologic composition to the agents used in this study
  • No concurrent treatment on another clinical trial; supportive care trials or non-therapeutic trials (e.g., quality of life) are allowed
  • No prior malignancy except for: adequately treated basal or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years. Patients with localized prostate cancer who are being followed by an active surveillance program are also eligible
  • Step 2 Patient Registration Eligibility Criteria
  • Patients must have completed 4 or more cycles of protocol-directed chemotherapy
  • Step 3 Patient Registration Eligibility Criteria (only patients with a DDR gene alteration)
  • Deleterious alteration within 1 or more of 9 pre-defined DDR genes within the pre-treatment TURBT deoxyribonucleic acid (DNA)
  • Cystoscopy and imaging performed to determine stage/treatment assignment

Locations

  • University of California Davis Comprehensive Cancer Center accepting new patients
    Sacramento California 95817 United States
  • Fremont - Rideout Cancer Center accepting new patients
    Marysville California 95901 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Alliance for Clinical Trials in Oncology
Links
Sign up for this study
ID
NCT03609216
Phase
Phase 2
Study Type
Interventional
Last Updated