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.