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

Primary Purpose

Bladder Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Cisplatin
Gemcitabine
Bevacizumab
Sponsored by
Christopher Sweeney, MBBS
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Bladder Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Chicago
  • Medical & Surgical Specialists, LLC
  • Oncology Hematology Associates of SW Indiana
  • Fort Wayne Oncology & Hematology, Inc
  • Indiana University Cancer Center
  • Quality Cancer Center (MCGOP)
  • Arnett Cancer Care
  • Northern Indiana Cancer Research Consortium
  • AP&S Clinic
  • Siteman Cancer Center
  • Oncology Hematology Care, Inc.

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Single Group Assignment

Arm Description

Cisplatin + Gemcitabine + Bevacizumab

Outcomes

Primary Outcome Measures

Progression Free Survival
- To determine the progression free survival of patients with metastatic transitional cell cancer treated with cisplatin, gemcitabine and bevacizumab.

Secondary Outcome Measures

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

Full Information

First Posted
October 5, 2005
Last Updated
February 16, 2016
Sponsor
Christopher Sweeney, MBBS
Collaborators
Genentech, Inc., Eli Lilly and Company, Walther Cancer Institute, Hoosier Cancer Research Network
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1. Study Identification

Unique Protocol Identification Number
NCT00234494
Brief Title
Cisplatin, Gemcitabine and Bevacizumab in Combination for Metastatic Transitional Cell Cancer
Official Title
A Phase II Trial of Cisplatin, Gemcitabine and Bevacizumab in Combination for Metastatic Transitional Cell Cancer: Hoosier Oncology Group GU04-75
Study Type
Interventional

2. Study Status

Record Verification Date
February 2016
Overall Recruitment Status
Completed
Study Start Date
November 2005 (undefined)
Primary Completion Date
December 2008 (Actual)
Study Completion Date
December 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Christopher Sweeney, MBBS
Collaborators
Genentech, Inc., Eli Lilly and Company, Walther Cancer Institute, Hoosier Cancer Research Network

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bladder Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
45 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Single Group Assignment
Arm Type
Experimental
Arm Description
Cisplatin + Gemcitabine + Bevacizumab
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Intervention Description
Cisplatin 70 mg/m2, day 1
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Intervention Description
Gemcitabine 1250 mg/m2, day 1 and 8
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Intervention Description
Bevacizumab 15mg/kg, day 1
Primary Outcome Measure Information:
Title
Progression Free Survival
Description
- To determine the progression free survival of patients with metastatic transitional cell cancer treated with cisplatin, gemcitabine and bevacizumab.
Time Frame
36 months
Secondary Outcome Measure Information:
Title
Overall Survival Time
Description
To estimate overall survival time in months.
Time Frame
36 months
Title
Estimate Response Rates
Description
To estimate rate of partial response (PR), complete response (CR) and overall response (PR plus CR).
Time Frame
36 months
Title
Duration of Response for Responding Patients
Description
To estimate duration of response for responding patients.
Time Frame
36 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christopher Sweeney, M.B.B.S.
Organizational Affiliation
Hoosier Oncology Group, LLC
Official's Role
Study Chair
Facility Information:
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Medical & Surgical Specialists, LLC
City
Galesburg
State/Province
Illinois
ZIP/Postal Code
61401
Country
United States
Facility Name
Oncology Hematology Associates of SW Indiana
City
Evansville
State/Province
Indiana
ZIP/Postal Code
47714
Country
United States
Facility Name
Fort Wayne Oncology & Hematology, Inc
City
Fort Wayne
State/Province
Indiana
ZIP/Postal Code
46815
Country
United States
Facility Name
Indiana University Cancer Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Quality Cancer Center (MCGOP)
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Arnett Cancer Care
City
Lafayette
State/Province
Indiana
ZIP/Postal Code
47904
Country
United States
Facility Name
Northern Indiana Cancer Research Consortium
City
South Bend
State/Province
Indiana
ZIP/Postal Code
46601
Country
United States
Facility Name
AP&S Clinic
City
Terre Haute
State/Province
Indiana
ZIP/Postal Code
47804
Country
United States
Facility Name
Siteman Cancer Center
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Oncology Hematology Care, Inc.
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45242
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
21422406
Citation
Hahn NM, Stadler WM, Zon RT, Waterhouse D, Picus J, Nattam S, Johnson CS, Perkins SM, Waddell MJ, Sweeney CJ; Hoosier Oncology Group. Phase II trial of cisplatin, gemcitabine, and bevacizumab as first-line therapy for metastatic urothelial carcinoma: Hoosier Oncology Group GU 04-75. J Clin Oncol. 2011 Apr 20;29(12):1525-30. doi: 10.1200/JCO.2010.31.6067. Epub 2011 Mar 21.
Results Reference
result
Links:
URL
http://www.hoosiercancer.org
Description
Hoosier Cancer Research Network Homepage

Learn more about this trial

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

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