Cisplatin, Gemcitabine and Bevacizumab in Combination for Metastatic Transitional Cell Cancer
This study has been completed.
Sponsor:
Hoosier Oncology Group
Collaborators:
Genentech
Eli Lilly and Company
Walther Cancer Institute
Information provided by:
Hoosier Oncology Group
ClinicalTrials.gov Identifier:
NCT00234494
First received: October 5, 2005
Last updated: January 22, 2009
Last verified: January 2009
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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 Oncology Group:
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
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 Oncology Group
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 |
Physiological Effects of Drugs Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antiviral Agents Anti-Infective Agents Enzyme Inhibitors Immunosuppressive Agents Immunologic Factors Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Growth Inhibitors |
ClinicalTrials.gov processed this record on May 16, 2013