Radiation Therapy and Chemotherapy in Treating Patients With Stage I Bladder Cancer
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Purpose
RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs used in chemotherapy, such as cisplatin, mitomycin C, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving radiation therapy together with cisplatin may kill more tumor cells.
PURPOSE: This phase II trial is studying how well radiation therapy given together with chemotherapy works in treating patients with stage I bladder cancer.
| Condition | Intervention | Phase |
|---|---|---|
|
Bladder Cancer |
Drug: cisplatin Drug: fluorouracil Drug: mitomycin C |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase II Protocol for Patients With Stage T1 Bladder Cancer to Evaluate Selective Bladder Preserving Treatment by Radiation Therapy Concurrent With Radiosensitizing Chemotherapy Following a Thorough Transurethral Surgical Re-Staging |
- Rate of freedom from radical cystectomy at 3 years [ Designated as safety issue: No ]
- Rate of freedom from radical cystectomy at 5 years [ Designated as safety issue: No ]
- Rate of freedom from the development of distant disease progression at 3 and 5 years [ Designated as safety issue: No ]
- Rate of freedom from progression of bladder tumor to stage T2 or greater at 3 and 5 years [ Designated as safety issue: No ]
- Disease-specific survival at 5 years [ Designated as safety issue: No ]
- Overall survival [ Designated as safety issue: No ]
- Incidence of adverse events as assessed by CTCAE, v3.0 [ Designated as safety issue: Yes ]
- Recurrence rate of any local bladder tumor [ Designated as safety issue: No ]
- Collection of pretreatment and post-treatment tissue, blood, and urine specimens for translational studies and for correlation with response and clinical outcome [ Designated as safety issue: No ]
- Descriptive analysis for American Urological Association symptom score at baseline and at 3 years [ Designated as safety issue: No ]
| Estimated Enrollment: | 37 |
| Study Start Date: | November 2009 |
| Estimated Primary Completion Date: | October 2018 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Regimen I
Patients receive cisplatin IV on days 1-3 of weeks 1, 3, and 5.
|
Drug: cisplatin
Given IV
|
|
Experimental: Regimen II
Patients receive mitomycin C IV on day 1 of radiotherapy and fluorouracil IV continuously over days 1-5 of weeks 1 and 4.
|
Drug: fluorouracil
Given IV
Drug: mitomycin C
Given IV
|
Detailed Description:
OBJECTIVES:
Primary
- To evaluate the rate of freedom from radical cystectomy at 3 years.
Secondary
- To evaluate the rate of freedom from radical cystectomy at 5 years.
- To evaluate the rate of freedom from the development of distant disease progression at 3 and 5 years.
- To evaluate the rate of freedom from progression of bladder tumor to stage T2 or greater at 3 and 5 years.
- To evaluate disease-specific survival and overall survival.
- To evaluate the incidence of acute and late pelvic toxicity.
- To evaluate the efficacy of this treatment approach in preventing the recurrence of any local bladder tumor.
- To evaluate the potential value of tumor histopathology plus molecular genetic, DNA content, and urine proteomics parameters as possible significant prognostic factors for tumor control with this treatment approach.
- To collect American Urological Association symptom scores at baseline and at 3 years.
OUTLINE: Beginning within 10 weeks of transurethral resection of the bladder tumor, patients undergo 3-dimensional conformal radiotherapy once daily 5 days per week during weeks 1-7 (34 fractions). Patients also receive 1 of 2 radiosensitizing chemotherapy regimens concurrently with radiotherapy.
- Regimen I: Patients receive cisplatin IV on days 1-3 of weeks 1, 3, and 5.
- Regimen II: Patients receive mitomycin C IV on day 1 of radiotherapy and fluorouracil IV continuously over days 1-5 of weeks 1 and 4.
Patients with a persistent tumor on re-evaluation may undergo radical cystectomy.
Tissue, blood, and urine samples may be collected periodically for biomarker and other analysis.
After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and annually thereafter.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS:
Carcinoma of the bladder pathologically (histologically or cytologically) diagnosed within the past 10 weeks, meeting either of the following criteria:
- Patients with operable tumors that are primary transitional cell carcinoma of the bladder exhibiting histologic evidence of invasion into the lamina propria (disease clinical stage T1) without evidence of muscularis propria invasion (muscularis propria must be present in the transurethral resection of the bladder tumor [TURBT] specimen) and are AJCC clinical stage T1, NX or N0, M0 without hydronephrosis
- Patients with disease involvement of the prostatic urethra with transitional cell carcinoma and have no evidence of stromal invasion of the prostate
- No pN+ or > T1 disease
No histologically or cytologically confirmed node metastases
- If radiologic evaluation of a lymph node is interpreted as "positive", this must be evaluated further either by lymphadenectomy or by percutaneous needle biopsy
- No evidence of distant metastases
- Must have a T1G2 or T1G3 transitional cell carcinoma that has recurred within 18 months after initial treatment for ≤ T1 tumors (TURBT and intravesical BCG immunotherapy) or have presented to a participating urologist who judged BCG therapy is contraindicated because patient may be immunocompromised
- Patients for whom radical cystectomy is the standard next therapy per urologic guidelines, in the judgement of the participating urologist, are eligible
- Must have an adequately functioning bladder as judged by the participating urologist and radiation oncologist and have undergone a visibly complete re-staging TURBT by the participating urologist that shows (or is present on the outside pathology specimen) a T1G2 or T1G3 tumor with uninvolved muscularis propria in the specimen and, if on prostatic urethral biopsy mucosal carcinoma is present, there is no evidence on biopsy in the prostatic stroma of tumor invasion
PATIENT CHARACTERISTICS:
- Zubrod performance status 0-1
- WBC ≥ 4,000/mm^3
- ANC ≥ 1,800/mm^3
- Platelet count ≥ 100,000/mm^3
- Hemoglobin ≥ 10.0 g/dL (transfusion or other intervention allowed)
- Serum creatinine ≤ 1.5 mg/dL
- Serum bilirubin ≤ 2.0 mg/dL
- Glomerular filtration rate (GFR) > 25 mL/min (for patients receiving cisplatin, GFR > 60 mL/min)
- Not pregnant
- Negative pregnancy test
- Fertile patients must use effective contraception
- Able to tolerate systemic chemotherapy combined with radiotherapy and a radical cystectomy (if necessary), in the opinions of the urologist, radiation oncologist, and medical oncologist
- No prior or concurrent malignancy of any other site or histology (except for nonmelanomatous skin cancer, T1a prostate cancer, or carcinoma in situ of the uterine cervix) unless the patient has been disease-free for ≥ 5 years
No severe, active co-morbidity including any of the following:
- Unstable angina and/or congestive heart failure that required hospitalization within the past 6 months
- Transmural myocardial infarction that occurred within the past 6 months
- Acute bacterial or fungal infection requiring IV antibiotics at the time of registration
- Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding any study therapy at the time of registration
- Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
- AIDS based upon the current Centers for Disease Control definition (HIV testing not required)
- No prior allergic reaction to cisplatin, mitomycin, or fluorouracil
PRIOR CONCURRENT THERAPY:
- No prior systemic chemotherapy for bladder cancer
- Prior chemotherapy for a different cancer allowed
- No prior radiotherapy to the region of this cancer that would result in overlap of radiotherapy fields
- No concurrent drugs that have potential nephrotoxicity or ototoxicity (e.g., aminoglycoside)
Contacts and Locations| United States, Georgia | |
| Emory Crawford Long Hospital | Recruiting |
| Atlanta, Georgia, United States, 30308 | |
| Contact: Peter J. Rossi 404-686-4411 | |
| Winship Cancer Institute of Emory University | Recruiting |
| Atlanta, Georgia, United States, 30322 | |
| Contact: Clinical Trials Office - Winship Cancer Institute 404-778-1900 | |
| United States, Maryland | |
| St. Agnes Hospital Cancer Center | Recruiting |
| Baltimore, Maryland, United States, 21229 | |
| Contact: Richard S. Hudes, MD 410-368-2965 | |
| United States, Massachusetts | |
| Hudner Oncology Center at Saint Anne's Hospital - Fall River | Recruiting |
| Fall River, Massachusetts, United States, 02721 | |
| Contact: Clinical Trials Office - Hudner Oncology Center at Saint Anne' 508-674-5600 ext. 2019 | |
| United States, New Hampshire | |
| Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center | Recruiting |
| Lebanon, New Hampshire, United States, 03756-0002 | |
| Contact: Clinical Trials Office - Norris Cotton Cancer Center 603-650-7609 cancerhelp@dartmouth.edu | |
| United States, New York | |
| Beth Israel Medical Center - Petrie Division | Recruiting |
| New York, New York, United States, 10003-3803 | |
| Contact: Clinical Trials Office - Beth Israel Medical Center - Petrie D 212-844-6286 | |
| United States, Ohio | |
| Summa Center for Cancer Care at Akron City Hospital | Recruiting |
| Akron, Ohio, United States, 44309-2090 | |
| Contact: Clinical Trials Office - Akron City Hospital 330-375-6101 | |
| Barberton Citizens Hospital | Recruiting |
| Barberton, Ohio, United States, 44203 | |
| Contact: William F. Demas, MD 330-375-3557 | |
| Cancer Care Center, Incorporated | Recruiting |
| Salem, Ohio, United States, 44460 | |
| Contact: William F. Demas, MD 330-375-3557 | |
| Cancer Treatment Center | Recruiting |
| Wooster, Ohio, United States, 44691 | |
| Contact: Clinical Trials Office - Cancer Treatment Center 330-375-4221 | |
| United States, Pennsylvania | |
| Fox Chase Cancer Center - Philadelphia | Recruiting |
| Philadelphia, Pennsylvania, United States, 19111-2497 | |
| Contact: Clinical Trials Office - Fox Chase Cancer Center - Philadelphi 215-728-4790 | |
| United States, Texas | |
| University of Texas Medical Branch | Recruiting |
| Galveston, Texas, United States, 77555-0361 | |
| Contact: Clinical Trials Office - University of Texas Medical Branch 409-772-1950 | |
| United States, Vermont | |
| Norris Cotton Cancer Center - North | Recruiting |
| Saint Johnsbury, Vermont, United States, 05819 | |
| Contact: Alan C. Hartford, MD, PhD 603-650-6600 | |
| Study Chair: | William U. Shipley, MD, FACR | Massachusetts General Hospital |
More Information
Additional Information:
No publications provided
| Responsible Party: | Walter John Curran, Jr, Radiation Therapy Oncology Group |
| ClinicalTrials.gov Identifier: | NCT00981656 History of Changes |
| Other Study ID Numbers: | CDR0000654727, RTOG-0926 |
| Study First Received: | September 19, 2009 |
| Last Updated: | September 26, 2012 |
| Health Authority: | Unspecified |
Keywords provided by National Cancer Institute (NCI):
|
stage I bladder cancer transitional cell carcinoma of the bladder |
Additional relevant MeSH terms:
|
Urinary Bladder Neoplasms Urologic Neoplasms Urogenital Neoplasms Neoplasms by Site Neoplasms Urinary Bladder Diseases Urologic Diseases Mitomycins Mitomycin Cisplatin Fluorouracil Antibiotics, Antineoplastic Antineoplastic Agents |
Therapeutic Uses Pharmacologic Actions Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Alkylating Agents Radiation-Sensitizing Agents Physiological Effects of Drugs Antimetabolites Antimetabolites, Antineoplastic Immunosuppressive Agents Immunologic Factors |
ClinicalTrials.gov processed this record on June 17, 2013