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
18 Years
N/A
Both
Bladder Cancer
Trial Information
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
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 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.
Inclusion Criteria
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
- 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)
- 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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Rate of distant metastasis at 3 years
Safety Issue:
No
Principal Investigator
John J. Coen, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Helen and Harry Gray Cancer Center at Hartford Hospital
Authority:
Unspecified
Study ID:
CDR0000616858
NCT ID:
NCT00777491
Start Date:
December 2008
Completion Date:
Related Keywords:
- Bladder Cancer
- stage II bladder cancer
- stage III bladder cancer
- transitional cell carcinoma of the bladder
- Urinary Bladder Neoplasms
Name | Location |
|---|---|
| University of Michigan Comprehensive Cancer Center | Ann Arbor, Michigan 48109-0752 |
| Saint Joseph Mercy Cancer Center | Ann Arbor, Michigan 48106-0995 |
| West Michigan Cancer Center | Kalamazoo, Michigan 49007-3731 |
| Winship Cancer Institute of Emory University | Atlanta, Georgia 30322 |
| Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center | Boise, Idaho 83706 |
| Parkview Regional Cancer Center at Parkview Health | Fort Wayne, Indiana 46805 |
| Cancer Institute at St. John's Hospital | Springfield, Illinois 62701 |
| Hudner Oncology Center at Saint Anne's Hospital - Fall River | Fall River, Massachusetts 02721 |
| Georgia Cancer Center for Excellence at Grady Memorial Hospital | Atlanta, Georgia 30303 |
| St. Agnes Hospital Cancer Center | Baltimore, Maryland 21229 |
