Cisplatin, Bevacizumab, and Gemcitabine Followed by Surgery, Bevacizumab, and Paclitaxel in Treating Patients With Locally Advanced Nonmetastatic Bladder Cancer That Can Be Removed By Surgery

NCT00268450 | Terminated Phase 2 Results DMC

• 5 other identifiers: CDR0000454937MUSC-AVF-3312MUSC-HR-15537GENENTECH-AVF-3312MUSC-CTO-100892
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 4

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as cisplatin, gemcitabine, and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some find tumor cells and kill them or carry tumor-killing substances to them. Others interfere with the ability of tumor cells to grow and spread. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving combination chemotherapy together with bevacizumab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving these treatments after surgery may kill any tumor cells that remain after surgery. PURPOSE: This phase II trial is studying how well giving cisplatin, bevacizumab, and gemcitabine followed by surgery, bevacizumab, and paclitaxel works in treating patients with locally advanced nonmetastatic bladder cancer that can be removed by surgery.

Conditions

Bladder Cancer

Keywords

transitional cell carcinoma of the bladder; stage III bladder cancer; stage II bladder cancer; recurrent bladder cancer

Outcome Measures

Primary Outcomes (1)

• Complete Remission Rate

  From day of first treatment until after cycle 3

Secondary Outcomes (6)

• Urinary Survivin Levels

  Baseline, week 6 and week 12

• Urinary Cytogenitics

  baseline and week 12

• Progression Free Survival

  from first treatment until time of progression or death, whichever comes first

• Median Overall Surivial

  from first treatment until death

• Percentage of Planned Dose Received

  from first treatment until end of week 12

Study Arms (1)

study intervention

EXPERIMENTAL

Neo-adjuvant cisplatin, gemcitabine and bevacizumab followed by radical cystectomy. Patients without residual disease will enter follow up after surgery. Patients with residual disease will receive adjuvant therapy with bevacizumab and ciaplatin.

Biological: bevacizumab; Drug: cisplatin; Drug: gemcitabine hydrochloride; Drug: paclitaxel; Procedure: cysectomy

Interventions

bevacizumab BIOLOGICAL

Before surgery: given as a 15mg/kg IV over 90 minutes every 21 days for 4 cycles After surgery: given as a 15mg/kg IV over 90 minutes every 21 days for 3 cycles

Also known as: avastin

study intervention

cisplatin DRUG

Before surgery: given as a 70mg/m2 IV over 60 minutes every 21 days for 4 cycles

study intervention

gemcitabine hydrochloride DRUG

Before surgery: given as a 1000mg/m2 IV over 30 minutes on days 1 and 8 of a 21 day cycle for 4 cycles

study intervention

paclitaxel DRUG

After surgery: given as a 175 mg/m2 dose ver 3 hours every 21 days for 3 cycles

study intervention

cysectomy PROCEDURE

study intervention

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Medical University of South Carolina: lead

Study Sites (4)

Hollings Cancer Center at Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

McLeod Regional Medical Center

Florence, South Carolina, 29501, United States

Location

Lowcountry Hematology and Oncology, PA

Mt. Pleasant, South Carolina, 29464-3233, United States

Location

Gibbs Regional Cancer Center at Spartanburg Regional Medical Center

Spartanburg, South Carolina, 29303, United States

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

Bevacizumab; Cisplatin; Gemcitabine; Paclitaxel

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Results Point of Contact

• Title: Kate Anderton
• Organization: Medical University of South Carolina

anderton@musc.edu

843-792-2708

Study Officials

• Andrew S. Kraft, MD

  Medical University of South Carolina

  STUDY CHAIR

• Gustavo Leone

  Medical University of South Carolina, Hollings Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2005
• First Posted: December 22, 2005
• Study Start: September 21, 2005
• Primary Completion: April 1, 2012
• Study Completion: April 1, 2012
• Last Updated: July 12, 2018
• Results First Posted: July 12, 2018

Record last verified: 2018-05

Locations

US (4)