Cisplatin, Gemcitabine and Bevacizumab in Combination for Metastatic Transitional Cell Cancer

This study has been completed.
Sponsor:
Collaborators:
Genentech
Eli Lilly and Company
Walther Cancer Institute
Information provided by:
Hoosier Cancer Research Network
ClinicalTrials.gov Identifier:
NCT00234494
First received: October 5, 2005
Last updated: January 22, 2009
Last verified: January 2009
  Purpose

Cisplatin is a very important agent for the treatment of TCC as it has a single agent response rate of approximately 15%. However, it has been most important as a part of combination chemotherapy, MVAC initially and now in combination with gemcitabine. Single agent gemcitabine has demonstrated an overall response rate (ORR) of approximately 25%, including some complete responses (CR), with minimal toxicity in patients with advanced bladder cancer. Bevacizumab, a murine anti-human VEGF monoclonal antibody, has been advanced for use in combination with cytotoxic chemotherapy to delay time to disease progression in patients with metastatic solid tumors.

This trial is designed to further assess the efficacy, safety and tolerability of this regimen in this patient population.


Condition Intervention Phase
Bladder Cancer
Drug: Cisplatin
Drug: Gemcitabine
Drug: Bevacizumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Cisplatin, Gemcitabine and Bevacizumab in Combination for Metastatic Transitional Cell Cancer: Hoosier Oncology Group GU04-75

Resource links provided by NLM:


Further study details as provided by Hoosier Cancer Research Network:

Primary Outcome Measures:
  • - To determine the progression free survival of patients with metastatic transitional cell cancer treated with cisplatin, gemcitabine and bevacizumab. [ Time Frame: 36 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To estimate the time to event efficacy variables, including duration of response for responding patients, time to treatment failure and overall survival time [ Time Frame: 36 months ] [ Designated as safety issue: No ]
  • To characterize the quantitative and qualitative toxicities of cisplatin gemcitabine and bevacizumab in this patient population. [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]
  • To estimate rate of partial response (PR), complete response (CR) and overall response (PR plus CR). [ Time Frame: 36 months ] [ Designated as safety issue: No ]

Enrollment: 45
Study Start Date: November 2005
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Cisplatin + Gemcitabine + Bevacizumab
Drug: Cisplatin
Cisplatin 70 mg/m2, day 1
Drug: Gemcitabine
Gemcitabine 1250 mg/m2, day 1 and 8
Drug: Bevacizumab
Bevacizumab 15mg/kg, day 1

Detailed Description:

OUTLINE: This is a multi-center study.

  • Cisplatin 70 mg/m2 Day 1
  • Gemcitabine 1250 mg/m2 Day 1 and 8
  • Bevacizumab 15 mg/kg Day 1

Review toxicity every cycle (every 3 weeks) Review for radiographic response every 2 cycles (every six weeks)

Progressive disease = off protocol therapy

Patients will be treated for up to a maximum of 8 cycles of cisplatin and gemcitabine (24 weeks of therapy). If a patient has not progressed by the end of 24 weeks (completion of cisplatin and gemcitabine), then patient will be treated with bevacizumab at 15 mg/kg every three weeks for a maximum of 12 months of bevacizumab therapy (since study entry).

If at any time patient has undue toxicity or progressive disease, patient will be removed from the study and followed until progression and for survival.

If the patient has Grade 3 or 4 neurotoxicity and/or the creatinine rises above 2.0, then the cisplatin will be discontinued and the patient continued on study and treated with gemcitabine and bevacizumab at the same dose and schedule.

ECOG Performance Status 0 or 1

Hematopoietic:

  • White blood cell count > 3000/mm3
  • Absolute neutrophil count (ANC) > 1500 mm/3
  • Platelet count > 100,000/mm3
  • Hemoglobin > 8 g/dL (may be transfused or receive erythropoietin support to maintain or exceed this level).
  • INR < 1.5
  • No full dose/therapeutic anticoagulation with either low molecular weight heparin or unfractionated heparin or coumadin

Hepatic:

  • Total bilirubin of <1.5 mg/dL
  • ALT <5 times upper limit of normal for subjects with documented liver metastases; <2.5 times the upper limit of normal for subjects without evidence of liver metastases.

Renal:

  • Serum creatinine of < 1.5 mg/dL.
  • Urine protein:creatinine ratio < 1.0 at screening

Cardiovascular:

  • No history of myocardial infarction or stroke within the last 6 months
  • No uncontrolled hypertension (blood pressure of >160 systolic and/or 110 diastolic mmHg on medication)
  • No unstable angina, New York Heart Association (NYHA) Grade II or greater congestive heart failure
  • No unstable symptomatic arrhythmia requiring medication (subjects with chronic atrial arrhythmia, i.e., atrial fibrillation or paroxysmal supraventricular tachycardia are eligible), or clinically significant peripheral vascular disease.

Pulmonary:

  • Not specified
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Previously untreated or relapsed locally advanced or metastatic transitional cell carcinoma of the bladder. (Patients with pathology showing ANY component of non-transitional cell histology are not eligible).
  • Relapsed patients may have received prior chemotherapy ≥ one year prior to study registration as part of a neoadjuvant or adjuvant regimen and must not have had intervening therapy from the end of that treatment until study entry.
  • Measurable disease as per RECIST.
  • Prior radiation therapy, immunotherapy, cytokine, biologic or vaccine therapy must be greater than 28 days prior to being registered for protocol therapy,

Exclusion Criteria:

  • No known central nervous system metastasis. (imaging of brain only required if clinically indicated)
  • No prior organ allograft.
  • No history of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the subject at high risk from treatment complications.
  • No evidence of bleeding diathesis or coagulopathy.
  • No history of serious, non-healing wound, ulcer or bone fracture
  • No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to being registered for protocol therapy.
  • No prior history of malignancy in the past 5 years with the exception of basal cell and squamous cell carcinoma of the skin. Other cancers with low potential for metastasis, such as in situ cancers (e.g., Grade 1, TA TCC (low grade superficial bladder cancer), colonic polyp with focus of adenocarcinoma) can also be enrolled after approval from the study chair.
  • No major surgical procedure, open biopsy, or significant traumatic injury less than 28 days prior to being registered for protocol therapy.
  • Patients are not eligible if the need for any major surgical procedure is anticipated during the course of the study.
  • Any minor surgical procedures, fine needle aspirations or core biopsies must be greater than 7 days prior to being registered for protocol therapy except procedures to secure a vascular access device which must be greater than 7 days prior to the start of protocol therapy.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00234494

Locations
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
Medical & Surgical Specialists, LLC
Galesburg, Illinois, United States, 61401
United States, Indiana
Oncology Hematology Associates of SW Indiana
Evansville, Indiana, United States, 47714
Fort Wayne Oncology & Hematology, Inc
Fort Wayne, Indiana, United States, 46815
Quality Cancer Center (MCGOP)
Indianapolis, Indiana, United States, 46202
Indiana University Cancer Center
Indianapolis, Indiana, United States, 46202
Arnett Cancer Care
Lafayette, Indiana, United States, 47904
Northern Indiana Cancer Research Consortium
South Bend, Indiana, United States, 46601
AP&S Clinic
Terre Haute, Indiana, United States, 47804
United States, Missouri
Siteman Cancer Center
St. Louis, Missouri, United States, 63110
United States, Ohio
Oncology Hematology Care, Inc.
Cincinnati, Ohio, United States, 45242
Sponsors and Collaborators
Hoosier Cancer Research Network
Genentech
Eli Lilly and Company
Walther Cancer Institute
Investigators
Study Chair: Christopher Sweeney, M.B.B.S. Hoosier Oncology Group, LLC
  More Information

Additional Information:
No publications provided

Responsible Party: Noah Hahn, M.D., Hoosier Oncology Group
ClinicalTrials.gov Identifier: NCT00234494     History of Changes
Other Study ID Numbers: HOG GU04-75
Study First Received: October 5, 2005
Last Updated: January 22, 2009
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Gemcitabine
Bevacizumab
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on August 28, 2014