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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


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Bladder Cancer

Thank you

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 CenterAnn Arbor, Michigan  48109-0752
Saint Joseph Mercy Cancer CenterAnn Arbor, Michigan  48106-0995
West Michigan Cancer CenterKalamazoo, Michigan  49007-3731
Winship Cancer Institute of Emory UniversityAtlanta, Georgia  30322
Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical CenterBoise, Idaho  83706
Parkview Regional Cancer Center at Parkview HealthFort Wayne, Indiana  46805
Cancer Institute at St. John's HospitalSpringfield, Illinois  62701
Hudner Oncology Center at Saint Anne's Hospital - Fall RiverFall River, Massachusetts  02721
Georgia Cancer Center for Excellence at Grady Memorial HospitalAtlanta, Georgia  30303
St. Agnes Hospital Cancer CenterBaltimore, Maryland  21229