Chemotherapy and Radiation Therapy in Treating Patients With Stage II or Stage III Bladder Cancer That Was Removed by Surgery

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:
NCT00777491
First received: October 21, 2008
Last updated: April 7, 2014
Last verified: April 2014

October 21, 2008
April 7, 2014
December 2008
January 2018   (final data collection date for primary outcome measure)
Rate of distant metastasis at 3 years [ Time Frame: From date of randomization to the date of completion of the 3 year follow-up. ] [ Designated as safety issue: No ]
Rate of distant metastasis at 3 years [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00777491 on ClinicalTrials.gov Archive Site
  • Treatment completion rate [ Time Frame: From the date of randomization to the date when patients complete consolidation chemotherapy or have a cyctectome with four cycles of gemcitabine and cisplatin. ] [ Designated as safety issue: No ]
  • Grade 3 or more genitourinary, gastrointestinal, and hematologic toxicities as assessed by NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v4.0 [ Time Frame: Acute toxicities - From treatment start date to the end of treatment. Late adverse events - 180 days from the end of treatment. ] [ Designated as safety issue: Yes ]
  • Complete response of the primary tumor [ Time Frame: Three to four weeks from completion of induction chemotherapy. ] [ Designated as safety issue: No ]
  • Preservation of the native, tumor-free bladder 5 years after completion of study therapy [ Time Frame: Five years from the date of trasurethral surgery. ] [ Designated as safety issue: No ]
  • Treatment completion rate [ Designated as safety issue: No ]
  • Grade 3 or more genitourinary, gastrointestinal, and hematologic toxicities as assessed by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
  • Complete response of the primary tumor [ Designated as safety issue: No ]
  • Preservation of the native, tumor-free bladder 5 years after completion of study therapy [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Chemotherapy and Radiation Therapy in Treating Patients With Stage II or Stage III Bladder Cancer That Was Removed by Surgery
A Phase II Randomized Study For Patients With Muscle-Invasive Bladder Cancer Evaluating Transurethral Surgery And Concomitant Chemoradiation By Either BID Irradiation Plus 5-Fluorouracil And Cisplatin Or QD Irradiation Plus Gemcitabine Followed By Selective Bladder Preservation And Gemcitabine/Cisplatin Adjuvant Chemotherapy

RATIONALE: Drugs used in chemotherapy, such as fluorouracil, cisplatin, and gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving chemotherapy together with radiation therapy may kill more tumor cells.

PURPOSE: This randomized phase II trial is studying two different chemotherapy and radiation therapy regimens to see how they work in treating patients with stage II or stage III bladder cancer that was removed by surgery.

OBJECTIVES:

Primary

  • To estimate the rate of distant metastasis at 3 years in patients who have undergone transurethral resection of the bladder tumor for stage II or III muscle-invasive bladder cancer treated with chemoradiotherapy comprising fluorouracil, cisplatin, and radiotherapy vs gemcitabine hydrochloride and radiotherapy followed by selective bladder preservation and adjuvant chemotherapy comprising gemcitabine hydrochloride and cisplatin.

Secondary

  • To estimate the treatment completion rate in these patients.
  • To estimate acute and late grade toxicities (≥ grade 3 genitourinary, gastrointestinal, and hematologic toxicities) of these regimens in these patients.
  • To estimate the efficacy of these regimens, in terms of achieving complete response of the primary tumor, in these patients.
  • To estimate the efficacy of these regimens, in terms of preserving the native, tumor-free bladder 5 years after completion of therapy, in these patients.
  • To estimate the value of tumor histopathologic, molecular genetic, DNA content, metabolomic, and proteomic parameters as possible significant prognostic factors for initial tumor response and recurrence-free survival.
  • To analyze for American Urological Association (AUA) Symptom scores at baseline and at 3 years from patients on both arms.
  • To find potentially predictive biomarkers for cystectomy-free survival.
  • To find potentially predictive biomarkers for acute and late toxicities.

OUTLINE: This is a multicenter study. Patients are stratified according to tumor stage (T2 vs T3-4a). Patients are randomized to 1 of 2 treatment arms.

  • Induction therapy (weeks 1-4):

    • Arm I: Patients receive fluorouracil IV continuously over 72 hours on days 1-3 and 15-17 and cisplatin IV over 1 hour on days 1-3, 8-10, and 15-17. Patients also undergo radiotherapy twice daily on days 1-5, 8-12, and 15-17.
    • Arm II: Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 4, 8, 11, 15, 18, 22, and 25. Patients also undergo radiotherapy once daily on days 1-5, 8-12, 15-19, and 22-26.

All patients undergo evaluation of response at 3-4 weeks after completion of induction therapy. Patients with pT1 or worse tumor response undergo radical cystectomy within 3-8 weeks after response evaluation. Patients with pT0, Ta, or Tis tumor response (at site distant from original tumor) proceed to consolidation therapy within 7-14 days after response evaluation.

  • Consolidation therapy (weeks 8-10):

    • Arm I: Patients receive fluorouracil IV continuously over 72 hours on days 1-3 and 8-10 and cisplatin IV over 1 hour on days 1, 2, 8, and 9. Patients also undergo radiotherapy twice daily on days 1-5 and 8-10.
    • Arm II: Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 4, 8, 11, and 15. Patients also undergo radiotherapy once daily on days 1-5, 8-12, 15, and 16.

Patients proceed to adjuvant therapy 12 weeks after completion of consolidation therapy OR 8-12 weeks after radical cystectomy.

  • Adjuvant therapy (weeks 21-33 or 17-29): Patients receive gemcitabine hydrochloride IV over 30-60 minutes on days 1 and 8 and cisplatin IV over 1 hour on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.

Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Bladder Cancer
  • Drug: cisplatin
    Given IV
  • Drug: fluorouracil
    Given IV
  • Drug: gemcitabine hydrochloride
    Given IV
  • Radiation: radiation therapy
    Given once or twice daily
  • Experimental: Arm I
    Patients receive induction therapy comprising fluorouracil IV, cisplatin IV, and radiotherapy in weeks 1-4. Patients then undergo either radical cystectomy or receive consolidation therapy comprising fluorouracil IV, cisplatin IV, and radiotherapy in weeks 8-10.
    Interventions:
    • Drug: cisplatin
    • Drug: fluorouracil
    • Radiation: radiation therapy
  • Experimental: Arm II
    Patients receive induction therapy comprising gemcitabine hydrochloride IV and radiotherapy in weeks 1-4. Patients then undergo either radical cystectomy or receive consolidation therapy comprising gemcitabine hydrochloride IV and radiotherapy in weeks 8-10.
    Interventions:
    • Drug: gemcitabine hydrochloride
    • Radiation: radiation therapy
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
64
Not Provided
January 2018   (final data collection date for primary outcome measure)

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed primary transitional cell carcinoma (TCC) of the bladder within the past 8 weeks

    • Exhibits histological evidence of muscularis propria invasion
  • Clinical stage T2-T4a, NX or N0, M0 disease

    • TCC involvement of the prostatic urethra allowed provided it was visibly completely resected AND there is no evidence of stromal invasion of the prostate
    • No histologically or cytologically confirmed lymph node metastases

      • Radiologic evidence of lymph node positivity allowed provided the lymph node is further evaluated by lymphadenectomy or percutaneous needle biopsy AND confirmed to be negative
    • No evidence of distant metastases
  • Operable disease

    • Has undergone transurethral resection of the bladder tumor within the past 8 weeks
    • Judged to be a candidate for radical cystectomy
  • Adequately functioning bladder after thorough evaluation by an urologist
  • No tumor-related hydronephrosis

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)
  • Creatinine clearance ≥ 60 mL/min
  • Serum creatinine ≤ 1.5 mg/dL (serum creatinine ≤ 1.8 mg/dL allowed provided creatinine clearance is > 60 mL/min)
  • Serum bilirubin ≤ 2.0 mg/dL
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Able to tolerate systemic chemotherapy combined with pelvic radiotherapy and a radical cystectomy as determined by the urologist, radiation oncologist, and medical oncologist
  • No other malignancy within the past 5 years except for nonmelanoma skin cancer, stage T1a prostate cancer, or carcinoma in situ of the cervix
  • No severe, active co-morbidities, including any of the following:

    • Unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months
    • Transmural myocardial infarction within the past 6 months
    • Acute bacterial or fungal infection requiring IV antibiotics
    • Chronic obstructive pulmonary disease exacerbation or other respiratory illness that requires hospitalization or precludes study therapy
    • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
    • AIDS
  • No prior allergic reaction to any of the study drugs

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior pelvic radiotherapy
  • No prior systemic chemotherapy for any cancer
  • No concurrent drugs that have potential nephrotoxicity or ototoxicity (e.g., aminoglycosides)
  • No concurrent intensity-modulated radiotherapy
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
 
NCT00777491
RTOG 0712, CDR0000616858
Yes
Radiation Therapy Oncology Group
Radiation Therapy Oncology Group
National Cancer Institute (NCI)
Principal Investigator: John J. Coen, MD Helen and Harry Gray Cancer Center at Hartford Hospital
Study Chair: Donald S. Kaufman, MD Massachusetts General Hospital
Study Chair: Cheryl T. Lee, MD University of Michigan Cancer Center
Study Chair: Chin-Lee Wu, MD, PhD Massachusetts General Hospital
Radiation Therapy Oncology Group
April 2014

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