Neoadjuvant Gemcitabine and Fractionated, Weekly Cisplatin For Muscle Invasive Bladder Cancer and Patients Not Candidates For High Dose Cisplatin

Study Overview
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Brief Summary
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The standard treatment of muscle invasive bladder cancer is to administer chemotherapy for approximately 3 months then to have surgery to remove the bladder. Chemotherapy may reduce the size of the cancer in your bladder before surgery and can also help to reduce the chance that your bladder cancer will come back (metastasize) in other parts of your body after bladder surgery. This study will involve testing cisplatin in lower weekly doses with gemcitabine.The purpose of this study is to test the effects, good and bad, of low dose weekly cisplatin and gemcitabine.

Official Title
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BrUOG 300: Neoadjuvant Gemcitabine and Fractionated, Weekly Cisplatin For Muscle Invasive Bladder Cancer and Patients Not Candidates For High Dose Cisplatin

Conditions
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Invasive Bladder Cancer, Bladder Cancer

Intervention / Treatment
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* Drug: Gemcitabine and fractionated cisplatin (combination treatment)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically confirmed muscle-invasive urothelial (transitional cell) carcinoma of the bladder or upper genitourinary tract. Stage T2-T4a. Patients may have nodal disease but there must be no evidence of distant metastases and patients must be candidates for radical cystectomy as determined by urologic surgeon (note from/confirmation by surgeon required). No prior systemic therapy for urothelial carcinoma. Prior intravesical therapy is allowed. Patients are determined by their treating oncologist to not be a candidate high dose cisplatin (> 70mg/m2) due to medical comorbidities. Creatinine Clearance (CrCL or eCCr)) > 25 mL/min calculated using the Cockcroft-Gault formula Patients without serious medical risk factors involving any of the major organ systems such that the investigator considers it unsafe for the patient to receive the protocol treatment of this study with gemcitabine and weekly fractionated cisplatin. Preexisting neuropathy < grade 2. No prior invasive malignancy within the prior two years. However, prior history of non-muscle invasive bladder cancer and patients with an early stage malignancy that is not expected to require treatment in the next 2 years (such as early stage, resected breast cancer, or asymptomatic prostate cancer) are eligible. ECOG performance status 0 or 1. Age ≥ 18 years of age. Not pregnant and not nursing. Women of child bearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 7 days prior to beginning of treatment. Post-menopausal women (surgical menopause or lack of menses >12 months) do not need to have a pregnancy test, please document status. Required Initial Laboratory Values: Neutrophils ≥ 1,000/μl Platelet count ≥ 100,000/μl Total bilirubin ≤ 1.5 x ULN. AST (SGOT) & ALT (SGPT) ≤ 3.0 x ULN Exclusion Criteria: Metastatic disease. Prior hypersensitivity to platinums that in the investigators opinion would put the patient at risk if re-exposed Small cell cancer of the bladder or pure adenocarcinoma. Patients with mixed histologies such as urothelial carcinoma with sarcomatoid features, squamous differentiation or adenocarcinoma are allowed as long as transitional cell cancer is the predominant pathologic subtype.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gemcitabine and fractionated cisplatin (combination treatment)<br>1 Cycle = 21 days. GC x 4 cycles ----> cystectomy Gemcitabine: 1000mg/m2, days 1 and 8 Cisplatin: 35mg/m2, days 1 and 8 | Drug: Gemcitabine and fractionated cisplatin (combination treatment)<br>* 1 Cycle = 21 days. GC x 4 cycles ----> cystectomy Gemcitabine: 1000mg/m2, days 1 and 8 Cisplatin: 35mg/m2, days 1 and 8<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathologic Complete Response Rate of Neoadjuvant Gemcitabine and Fractionated Cisplatin for Patients With Muscle Invasive Bladder Cancer Whom Are Not Candidates for High Dose Cisplatin. | Response will be evaluated in this study using the international criteria proposed in the Revised Response Evaluation Criteria in Solid Tumors (RECIST) Guideline version 1.1 [Eur J Cancer. 2009;45:228-247.].Complete Response (CR): Disappearance of all target lesions; Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions). Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficie | at approximately 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Experiencing Toxicities With Neoadjuvant Gemcitabine and Fractionated Cisplatin for Patients With Bladder Cancer | Toxicities assessed while patients are on treatments | Prior to each of the 4 cycles of treatment, after 4 months of treatment, 30 days post the last dose of drug (for a total of approximately 5 months) |