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Radiation Therapy and Chemotherapy in Treating Patients With Stage I Bladder Cancer

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ClinicalTrials.gov Identifier: NCT00981656
Recruitment Status : Active, not recruiting
First Posted : September 22, 2009
Last Update Posted : September 30, 2020
Sponsor:
Collaborators:
National Cancer Institute (NCI)
NRG Oncology
Information provided by (Responsible Party):
Radiation Therapy Oncology Group

Tracking Information
First Submitted Date  ICMJE September 19, 2009
First Posted Date  ICMJE September 22, 2009
Last Update Posted Date September 30, 2020
Actual Study Start Date  ICMJE November 2009
Estimated Primary Completion Date March 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 13, 2013)
Rate of freedom from radical cystectomy at 3 years [ Time Frame: Three years from the date of registration. ]
Original Primary Outcome Measures  ICMJE
 (submitted: September 19, 2009)
Rate of freedom from radical cystectomy at 3 years
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 13, 2013)
  • Rate of freedom from radical cystectomy at 5 years [ Time Frame: Five years from the date of registration. ]
  • Rate of freedom from the development of distant disease progression at 3 and 5 years [ Time Frame: From the date of registration to the date of first appearance of disease in a non-regional lymph node, solid organ or bone within 3 years and 5 years after registration. ]
  • Rate of freedom from progression of bladder tumor to stage T2 or greater at 3 and 5 years [ Time Frame: From the date of registration to the date of first documented increase of 50% or more in the largest diameter of the endoscopically appreciable tumor or the progression from stage T1 to stage T2 or beyond within 3 years and 5years afeter registration. ]
  • Disease-specific survival at 5 years [ Time Frame: From the date of registration to the date of death due to bladder cancer. ]
  • Overall survival [ Time Frame: From the date of registration to the date of death due to any cause. ]
  • Incidence of adverse events as assessed by Common Toxicity Criteria for Adverse Effects (CTCAE), v3.0 [ Time Frame: From the date of registration to the date of Grade 3 or more adverse events based on the active version of CTCAE among all eligible patients. ]
  • Recurrence rate of any local bladder tumor [ Time Frame: From the date of registration to the date of first documented local bladder recurrence. ]
  • Descriptive analysis for American Urological Association symptom score at baseline and at 3 years [ Time Frame: From the date of registration to 3 years after registration. ]
Original Secondary Outcome Measures  ICMJE
 (submitted: September 19, 2009)
  • Rate of freedom from radical cystectomy at 5 years
  • Rate of freedom from the development of distant disease progression at 3 and 5 years
  • Rate of freedom from progression of bladder tumor to stage T2 or greater at 3 and 5 years
  • Disease-specific survival at 5 years
  • Overall survival
  • Incidence of adverse events as assessed by CTCAE, v3.0
  • Recurrence rate of any local bladder tumor
  • Collection of pretreatment and post-treatment tissue, blood, and urine specimens for translational studies and for correlation with response and clinical outcome
  • Descriptive analysis for American Urological Association symptom score at baseline and at 3 years
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Radiation Therapy and Chemotherapy in Treating Patients With Stage I Bladder Cancer
Official Title  ICMJE 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
Brief Summary

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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Bladder Cancer
Intervention  ICMJE
  • Drug: cisplatin
    Given IV
  • Drug: fluorouracil
    Given IV
  • Drug: mitomycin C
    Given IV
Study Arms  ICMJE Experimental: TURBT + Concurrent RT + Chemotherapy
Transurethral resection of the bladder tumor (TURBT) + Concurrent Radiation Therapy (RT) + Chemotherapy
Interventions:
  • Drug: cisplatin
  • Drug: fluorouracil
  • Drug: mitomycin C
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: September 19, 2009)
37
Original Estimated Enrollment  ICMJE Same as current
Study Completion Date  ICMJE Not Provided
Estimated Primary Completion Date March 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

DISEASE CHARACTERISTICS:

  • Pathologically (histologically or cytologically) diagnosis of carcinoma of the bladder within 105 days prior to registration.

    • Patients with operable tumors that are primary high grade urothelial carcinoma of the bladder exhibiting histologic evidence of invasion into the lamina propria (disease clinical stage T1) or a high grade stage Ta urothelial carcinoma without hydronephrosis.
    • Patients with disease involvement of the prostatic urethra with urothelial carcinoma and have no evidence of stromal invasion of the prostate. If the patient's initial tumor was a high grade Ta urothelial carcinoma then his/her recurrent tumor must be a high grade stage T1 urothelial carcinoma to be eligible.
    • Patients must have a high grade urothelial carcinoma stage Ta or T1 that has recurred within 540 days after completion of the initial treatment (transurethral resection bladder tumor [TURBT] and intravesical bacillus Calmette-Guerin [BCG] immunotherapy) or have presented to a participating urologist who judged BCG therapy is contraindicated because this patient may be immuno-compromised or because the patients refuses BCG therapy
  • No confirmed tumor-related hydronephrosis
  • 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
  • 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
  • White blood cell count (WBC) ≥ 4,000/mm^3
  • Absolute neutrophil count (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 5-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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 120 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00981656
Other Study ID Numbers  ICMJE RTOG 0926
CDR0000654727
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Radiation Therapy Oncology Group
Study Sponsor  ICMJE Radiation Therapy Oncology Group
Collaborators  ICMJE
  • National Cancer Institute (NCI)
  • NRG Oncology
Investigators  ICMJE
Principal Investigator: William U. Shipley, MD, FACR Massachusetts General Hospital
PRS Account Radiation Therapy Oncology Group
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP