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

February 16, 2016 updated by: Christopher Sweeney, MBBS

A Phase II Trial of Cisplatin, Gemcitabine and Bevacizumab in Combination for Metastatic Transitional Cell Cancer: Hoosier Oncology Group GU04-75

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment (Actual)

45

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago
      • Galesburg, Illinois, United States, 61401
        • Medical & Surgical Specialists, LLC
    • Indiana
      • Evansville, Indiana, United States, 47714
        • Oncology Hematology Associates of SW Indiana
      • Fort Wayne, Indiana, United States, 46815
        • Fort Wayne Oncology & Hematology, Inc
      • Indianapolis, Indiana, United States, 46202
        • Indiana University Cancer Center
      • Indianapolis, Indiana, United States, 46202
        • Quality Cancer Center (MCGOP)
      • Lafayette, Indiana, United States, 47904
        • Arnett Cancer Care
      • South Bend, Indiana, United States, 46601
        • Northern Indiana Cancer Research Consortium
      • Terre Haute, Indiana, United States, 47804
        • AP&S Clinic
    • Missouri
      • St. Louis, Missouri, United States, 63110
        • Siteman Cancer Center
    • Ohio
      • Cincinnati, Ohio, United States, 45242
        • Oncology Hematology Care, Inc.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Single Group Assignment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival
Time Frame: 36 months
- To determine the progression free survival of patients with metastatic transitional cell cancer treated with cisplatin, gemcitabine and bevacizumab.
36 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival Time
Time Frame: 36 months
To estimate overall survival time in months.
36 months
Estimate Response Rates
Time Frame: 36 months
To estimate rate of partial response (PR), complete response (CR) and overall response (PR plus CR).
36 months
Duration of Response for Responding Patients
Time Frame: 36 months
To estimate duration of response for responding patients.
36 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Christopher Sweeney, MBBS

Collaborators

Eli Lilly and Company
Genentech, Inc.
Hoosier Cancer Research Network
Walther Cancer Institute

Investigators

  • Study Chair: Christopher Sweeney, M.B.B.S., Hoosier Oncology Group, LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2005

Primary Completion (Actual)

December 1, 2008

Study Completion (Actual)

December 1, 2008

Study Registration Dates

First Submitted

October 5, 2005

First Submitted That Met QC Criteria

October 5, 2005

First Posted (Estimate)

October 7, 2005

Study Record Updates

Last Update Posted (Estimate)

March 14, 2016

Last Update Submitted That Met QC Criteria

February 16, 2016

Last Verified

February 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HOG GU04-75

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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