Trial of Vascular Endothelial Growth Factor (VEGF), Bevacizumab, in Combination With Cytotoxic Chemotherapy for Endometrial Cancer
|Endometrial Carcinoma||Drug: carboplatin, paclitaxel, and bevacizumab||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A Phase II Trial of a Vascular Endothelial Growth Factor (VEGF) Monoclonal Antibody, AVASTIN, in Combination With Cytotoxic Chemotherapy CARBOPLATIN and PACLITAXEL for Recurrent/Advanced Endometrial Cancer|
- Number of Participants With Progression Free Survival (PFS=Date of Progression of Disease or Death) at 6 Months Using Bevacizumab, Carboplatin, and Paclitaxel in Patients With Measurable Disease for Advanced/Recurrent Endometrial Cancer [ Time Frame: 58 months ]Number of patients with progression free survival measured at 6 months. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST version 1.0), as a 20% increased in the sum of the longest diameter of target lesions, or a measure increase in a non-target lesion, or the appearance of new lesions.
- Median Progression Free Survival of This Treatment Regimen in Patients With Advanced/Recurrent Endometrial Cancer. [ Time Frame: 58 months ]Median progression free survival measured in months. Progression of disease is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST version 1.0), as a 20% increased in the sum of the longest diameter of the target lesions, or a measurable increased in a non-target lesion, or the appearance of a new lesion.
- Number of Participants With Adverse Events Grades 1-5 [ Time Frame: 58 months ]Toxicity and safety was monitored before every treatment cycle, during, and after treatment. Bevacizumab was discontinued if the following criteria was met: grade 4 hypertension, reversible posterior leukoencephalopathy syndrome or hypertensive encephalopathy, grade 4 nephritic syndrome, arterial thrombosis, symptomatic grade 4 or recurrent/worsening venous thromboembolic events after resumption of bevacizumab treatment, grade 3 hemorrhage, bowel perforation or fistula and any complete wound disruption.
|Study Start Date:||December 2007|
|Study Completion Date:||February 2012|
|Primary Completion Date:||February 2012 (Final data collection date for primary outcome measure)|
Drug: carboplatin, paclitaxel, and bevacizumab
All patients enrolled will receive carboplatin AUC 5 plus paclitaxel 175 mg/m2 (135 mg/m2 if prior radiation to greater than 25% of bone marrow) plus bevacizumab 15 mg/kg every 3 weeks.
Other Name: Avastin
- Patients with a concomitant malignancy other than non-melanoma skin cancer. Patients with a prior malignancy who have been disease-free for greater than 5 years or who received prior chemotherapy for that malignancy.
- Patients in whom pathological confirmation of the tumor is not obtainable. General Medical Exclusions
- Patients with concomitant medical illness such as serious uncontrolled infection, uncontrolled angina, or serious peripheral neuropathy, which, in the opinion of the treating physician, make the treatments prescribed on this study unreasonably hazardous for the patient.
- Patients with third degree or complete heart block are not eligible unless a pacemaker is in place. Patients on medications which alter cardiac conduction, such as digitalis, beta-blockers, or calcium channel blockers, or who have other conduction abnormalities or cardiac dysfunction may be placed on study at the discretion of the investigator.
- Patients whose circumstances will not permit study completion or adequate follow-up.
- Patients who are sensitive to E. Coli-derived drug preparations.
- Life expectancy of less than 12 weeks.
- Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored avastin cancer study.
- Inadequately controlled hypertension (defined as systolic blood pressure greater than 150 and/or diastolic blood pressure greater than 100 mmHg on antihypertensive medications).
- Any prior history of hypertensive crisis or hypertensive encephalopathy.
- New York Heart Association (NYHA) Grade II or greater congestive heart failure (see Appendix C).
- History of myocardial infarction or unstable angina within 6 months prior to study enrollment.
- History of stroke or transient ischemic attack within 6 months prior to study enrollment.
- Known CNS disease.
- Significant vascular disease (e.g., aortic aneurysm, aortic dissection). Symptomatic peripheral vascular disease
- Evidence of bleeding diathesis or coagulopathy. Blood coagulation parameters: PT such that international normalized ratio (INR) is less than 1.5 (or an in range INR, between 2 and 3, if a patient is on a stable dose of therapeutic warfarin) and a PTT less than 1.5 times the institutional upper limit of normal.
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study.
- Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment.
-History of abdominal fistula, gastrointestinal perforation, or intra- abdominal abscess within 6 months prior to study enrollment. Patients with clinical symptoms or signs of gastrointestinal obstruction and who require parenteral hydration and/or nutrition.
- Serious, non-healing wound, ulcer, or bone fracture.
- Proteinuria at screening as demonstrated by:
- Urine protein:creatinine (UPC) ratio greater than or equal to 1.0 at screening
- Known hypersensitivity to any component of avastin.
- Pregnant (positive pregnancy test) or lactating. Refusal to use of effective means of contraception (men and women) in subjects of child-bearing potential.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00879359
|United States, Ohio|
|Cleveland, Ohio, United States, 44129|
|Principal Investigator:||Peter Rose, MD||The Cleveland Clinic|