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A Phase II Study of Neo-Adjuvant Cisplatin, Gemcitabine & Bevacizumab, Followed by Radical Cystectomy for Patients With Muscle Invasive, Resectable, Non-Metastatic Transitional Cell Carcinoma (TCC) of the Bladder


Phase 2
18 Years
N/A
Not Enrolling
Both
Bladder Cancer

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Trial Information

A Phase II Study of Neo-Adjuvant Cisplatin, Gemcitabine & Bevacizumab, Followed by Radical Cystectomy for Patients With Muscle Invasive, Resectable, Non-Metastatic Transitional Cell Carcinoma (TCC) of the Bladder


OBJECTIVES:

Primary

- Determine the pT0 status (pathologic complete remission rate, no evidence of disease on
cystectomy specimen) in patients with muscle-invasive, resectable, nonmetastatic
transitional cell carcinoma (TCC) of the bladder treated with neoadjuvant cisplatin,
bevacizumab, and gemcitabine hydrochloride followed by radical cystectomy and adjuvant
bevacizumab and paclitaxel.

Secondary

- Determine if urinary survivin and urocytogenetics can predict responses in patients
with muscle invasive, resectable, non-metastatic TCC of the bladder treated with
neoadjuvant cisplatin and gemcitabine chemotherapy with bevacizumab.

- Evaluate the progression-free and median survival in patients treated with neo-adjuvant
cisplatin and gemcitabine hydrochloride chemotherapy with bevacizumab followed by
radical cystectomy.

- Determine the feasibility, tolerability and toxicity of neoadjuvant cisplatin and
gemcitabine hydrochloride with bevacizumab in patients with muscle invasive,
resectable, nonmetastatic transitional cell carcinoma (TCC) of the bladder.

- Correlate pT0 on cystoscopy with pT0 on radical cystectomy in patients treated with
neoadjuvant cisplatin and gemcitabine hydrochloride chemotherapy with bevacizumab in
patients with muscle invasive, resectable, nonmetastatic transitional cell carcinoma
(TCC) of the bladder.

- Determine the influence of adjuvant paclitaxel plus bevacizumab (in pathologic
non-complete responders) on progression-free and overall survival rates.

- Determine the safety of bevacizumab use in the adjuvant setting in therapy of locally
advanced bladder cancer.

- Determine the rate of postoperative complications, following treatment with neoadjuvant
therapy (cisplatin, gemcitabine hydrochloride, and bevacizumab) and radical cystectomy.

OUTLINE: This is a multicenter study.

- Neoadjuvant therapy: Patients receive cisplatin IV over 60 minutes and bevacizumab IV
over 30-90 minutes on day 1 and gemcitabine hydrochloride IV over 30 minutes on days 1
and 8. Treatment repeats every 3 weeks for 4 courses in the absence of disease
progression or unacceptable toxicity. Patients with nonmetastatic disease at 12 weeks
proceed to surgery at least 30 days later.

- Surgery: Patients undergo radical cystectomy. Patients who achieve pT0 status
(pathologic complete remission rate, no evidence of disease on cystectomy specimen) are
observed off study. Patients with evidence of disease proceed to adjuvant therapy.

- Adjuvant therapy: Patients receive bevacizumab IV over 30-90 minutes and paclitaxel IV
over 3 hours on day 1. Treatment repeats every 3 weeks for 3 courses in the absence of
disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for 6 years.

PROJECTED ACCRUAL: A total of 25 patients will be accrued for this study.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed transitional cell cancer (TCC) of the bladder

- Staged as follows:

- Muscle invasive (T2-T4a)

- Node negative (N0)

- No histologically or cytologically proven lymph node metastases

- Nonmetastatic (M0)

- No evidence of distant metastases

- Resectable disease

- Able to begin protocol treatment within 6 weeks after transurethral resection and
cystoscopic evaluation

- No central nervous system or brain metastases

PATIENT CHARACTERISTICS:

- ECOG performance status of 0-2

- Karnofsky 60-100%

- White blood cell count ≥ 3,000/mm^3

- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- AST(SGOT) and ALT(SGPT) ≤ 2 times upper limit of normal

- Bilirubin ≤1.5 mg/dL

- Creatinine clearance ≥ 60 mL/min

- Urine protein/creatinine ratio < 1.0

- Blood pressure ≤150/100 mm Hg

- No prohibitive medical risks for chemotherapy

- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to cisplatin, gemcitabine hydrochloride, or paclitaxel

- No unstable angina

- No history of myocardial infarction within the past 6 months

- No cardiac arrhythmias

- No New York Heart Association (NYHA) congestive heart failure ≥ grade 2

- No history of stroke within the past 6 months

- No clinically significant peripheral vascular disease

- No evidence of bleeding diathesis or coagulopathy

- No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within the past 6 months

- No serious nonhealing wound, ulcer, or bone fracture

- No psychiatric illness or other psychosocial situation that would limit ability to
comply with study and/or follow-up procedures

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must agree to use adequate contraception prior to study entry and
for the duration of study participation

- No significant traumatic injury with in the past 28 days

PRIOR CONCURRENT THERAPY:

- No prior systemic chemotherapy

- No prior pelvic radiation therapy

- More than 4 weeks since prior participation in an experimental drug study other than
a Genentech-sponsored bevacizumab cancer study

- No concurrent participation in an experimental drug study other than a
Genentech-sponsored bevacizumab cancer study

- No major surgical procedure or open biopsy within the past 28 days

- No anticipation of need for major surgical procedure during the course of the study

- No minor surgical procedures, fine-needle aspirations, or core biopsies within the
past 7 days

- No concurrent treatment with hormones or other chemotherapeutic agents except the
following:

- Steroids given for adrenal failure

- Hormones administered for nondisease-related conditions (e.g., insulin for
diabetes)

- Intermittent use of dexamethasone as an antiemetic in solid tumor protocols

- No other concurrent investigational or commercial agents or therapies

Type of Study:

Interventional

Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall pT0 response rate

Safety Issue:

No

Principal Investigator

Andrew S. Kraft, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Medical University of South Carolina

Authority:

United States: Food and Drug Administration

Study ID:

CDR0000454937

NCT ID:

NCT00268450

Start Date:

September 2005

Completion Date:

April 2012

Related Keywords:

  • Bladder Cancer
  • transitional cell carcinoma of the bladder
  • stage III bladder cancer
  • stage II bladder cancer
  • recurrent bladder cancer
  • Urinary Bladder Neoplasms
  • Carcinoma, Transitional Cell

Name

Location

Hollings Cancer Center at Medical University of South Carolina Charleston, South Carolina  29425
Gibbs Regional Cancer Center at Spartanburg Regional Medical Center Spartanburg, South Carolina  29303
McLeod Regional Medical Center Florence, South Carolina  29501
Lowcountry Hematology and Oncology, PA Mount Pleasant, South Carolina  29464-3233