Image-Guided Radiation Therapy for Bladder-Cancer Patients Undergoing Radiotherapy and Concurrent Gemcitabine Chemotherapy

Study Overview
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Brief Summary
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The purpose of this study is to test the safety of different amounts (doses) of external radiation therapy (high-energy x-rays that shrink or destroy cancer) combined with chemotherapy.

Official Title
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Phase I Dose-Escalation Study of Image-Guided Radiation Therapy for Bladder-Cancer Patients Undergoing Radiotherapy and Concurrent Gemcitabine Chemotherapy

Conditions
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Bladder Cancer

Intervention / Treatment
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* Other: external radiation therapy with gemcitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: MSKCC-reviewed pathologically proven diagnosis of primary bladder urothelial carcinoma without evidence of regional (nodal) or distant spread (cT1-T4a, Nx or N0). Karnofsky Performance Scale (KPS) ≥ 70% Age ≥18 years old Adequately functioning bladder, defined as continent and without the need for an indwelling catheter Absolute neutrophil count (ANC) ≥ 1500/mL; platelets ≥ 100,000/mm3 serum bilirubin < 1.5 x the upper limit of normal (ULN); aspartate aminotransferase (AST) and/alanine aminotransferase (ALT) ≤ 1.5 × ULN Adequate renal function: calculated creatinine clearance > 30 mL/min/1.73 m2 using the following formula modified Cockcroft and Gault Formula for estimated Creatinine Clearance Patients must be considered able to tolerate systemic chemotherapy and pelvic radiation therapy. Patients must have the ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Evidence of distant disease or histologically-proven nodal metastases. Patients with radiologic evidence of lymphadenopathy must have biopsy proof of N0 status. Previous pelvic radiation therapy Prior systemic chemotherapy non-cisplatin based neoadjuvant for urothelial carcinoma (prior intravesical chemotherapy or immunotherapy is permissible) Prior cisplatin based neoadjuvant systemic chemotherapy for more than >4 cycles Active inflammatory bowel disease (i.e., Crohn's disease or ulcerative colitis) Women who are pregnant or lactating

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: Radiotherapy and Concurrent Gemcitabine Chemotherapy<br>This is a Phase I dose-escalation study examining the safety and tolerability of intensity modulated external radiation therapy using image-guidance in combination with gemcitabine chemotherapy as an alternative to radical cystectomy. | Other: external radiation therapy with gemcitabine<br>* All patients will undergo daily image-guided radiation therapy with concurrent twice weekly gemcitabine chemotherapy. Radiation therapy will begin 2-4 weeks after restaging cystoscopy/fiducial marker placement. Dose level #1: 23.4 Gy/1.8 Gy × 13 fractions (total dose 68.4 Gy) Dose level #2: 27.0 Gy/1.8 Gy × 15 fractions (total dose 72.0 Gy) Dose level #3: 30.6 Gy/1.8 Gy × 17 fractions (total dose 75.6 Gy)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the dose limiting toxicity and establish the maximal tolerated dose |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the complete response rate of the primary tumor |  | 4-6 weeks following consolidation therapy | 
| To determine the long term toxicity |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bladder, Radiotherapy, Gemcitabine, Chemotherapy, 10-031