A Safety and Efficacy Study of Carboplatin, Paclitaxel, Bevacizumab and CA4P in Non-Small Cell Lung Cancer
- Conditions
- Tumors
- Interventions
- Registration Number
- NCT00653939
- Lead Sponsor
- Mateon Therapeutics
- Brief Summary
The purpose of this study is to determine the safety, tolerability and efficacy of combretastatin A4 phosphate (CA4P), also known as fosbretabulin, in combination with bevacizumab (Avastin), carboplatin and paclitaxel in patients with chemotherapy naïve non-small cell lung cancer (NSCLC). This is a randomized parallel arm study. All participants will receive carboplatin, paclitaxel and bevacizumab, and half will additionally receive CA4P. Patients who complete the first 6 cycles of therapy and have not experienced disease progression will receive maintenance therapy with bevacizumab alone or with bevacizumab plus CA4P.
The rationale for this study is the potential additive or synergistic actions of vascular disrupting agents like CA4P with anti-angiogenic agents like bevacizumab.
- Detailed Description
Lung cancer has become the leading cause of cancer death in both men and women in the US and Europe, accounting for 29% of all cancer deaths. Non-Small Cell Lung cancer (NSCLC) accounts for approximately 80% of all lung cancer cases. Currently, no curative treatment is available for advanced stages of the disease (stages III and IV), which comprise the majority of cases. Treatment with the combination of carboplatin and paclitaxel has been shown to be effective and well tolerated in advanced stage NSCLC. Targeted therapies, such as bevacizumab, often act synergistically with chemotherapy. Bevacizumab inhibits vascular endothelial growth factor (VEGF), necessary for endothelial cell proliferation and new blood vessel formation. CA4P targets existing abnormal vasculature of tumors, impeding tumor blood flow and leading to extensive tumor cell death as a consequence of oxygen and nutrient deprivation.
This study will compare the effect of CA4P when combined with chemotherapy and bevacizumab on progression free survival (PFS) to PFS after chemotherapy and bevacizumab alone.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 63
- Pathologically confirmed Stage IIIB NSCLC with malignant pleural effusion, or Stage IV disease
- Measurable disease on CT scan (by the Response Evaluation Criteria in Solid Tumors [RECIST] criteria)
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1 (which means able to independently care for self and to perform light work) .
- Adequate blood counts
- Adequate liver and kidney function
- Subjects or their legal representatives must be able to read, understand and provide written informed consent to participate in the trial.
- Predominant Squamous Cell NSCLC histology.
- History of treatment for NSCLC with chemotherapy, biological therapy, immunotherapy (surgery or radiation therapy are accepted)
- Brain (CNS) metastasis by head CT scan or MRI
- Subjects with history of prior malignancy except for curatively treated basal cell carcinoma of the skin; cervical intra-epithelial neoplasia; or localized prostate cancer with a current prostate specific antigen (PSA) of < 4.0 mg/dL. Subjects with other curatively treated malignancies who have no evidence of metastatic disease and >2 year disease free interval may be entered after discussion with the Medical Monitor.
- History of bleeding disorders, particularly coughing up ≥ ½ teaspoon bright red blood during the last 3 months
- Certain cardiac disorders such as recent myocardial infarction (MI), severe congestive heart failure, certain types of abnormal cardiac rhythm
- Uncontrolled high blood pressure despite medications
- Uncontrolled, clinically significant active infection.
- Known HIV
- Known hypersensitivity to any of the components of CA4P, paclitaxel, carboplatin, bevacizumab, or radiologic contrast dyes.
Details of the above and additional inclusion and exclusion criteria can be discussed with an investigator.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 1: Chemotherapy+Bevacizumab Carboplatin Carboplatin (AUC 6), paclitaxel (200 mg/m2), and bevacizumab (15 mg/kg)administered intravenously on Day 1 of a 21-day cycle for up to six treatment cycles. After 6 cycles, subjects who have not progressed may continue to receive bevacizumab (15 mg/kg) alone on Day 1 every 3 weeks until progression or until 12 months from randomization. Arm 1: Chemotherapy+Bevacizumab Paclitaxel Carboplatin (AUC 6), paclitaxel (200 mg/m2), and bevacizumab (15 mg/kg)administered intravenously on Day 1 of a 21-day cycle for up to six treatment cycles. After 6 cycles, subjects who have not progressed may continue to receive bevacizumab (15 mg/kg) alone on Day 1 every 3 weeks until progression or until 12 months from randomization. Arm 1: Chemotherapy+Bevacizumab Bevacizumab Carboplatin (AUC 6), paclitaxel (200 mg/m2), and bevacizumab (15 mg/kg)administered intravenously on Day 1 of a 21-day cycle for up to six treatment cycles. After 6 cycles, subjects who have not progressed may continue to receive bevacizumab (15 mg/kg) alone on Day 1 every 3 weeks until progression or until 12 months from randomization. Arm 2: Active Comparator+Fosbretabulin Carboplatin Carboplatin (AUC 6), paclitaxel (200 mg/m2), and bevacizumab (15 mg/kg), administered intravenously Day 1 of a 21-day cycle and fosbretabulin (60 mg/m2) on Days 7, 14, and 21 for up to six treatment cycles. After 6 cycles, subjects who have not progressed may continue to receive bevacizumab (15 mg/kg) on Day 1 and fosbretabulin on Days 1, 7 and 14 every 3 weeks until progression or until 12 months from randomization. Arm 2: Active Comparator+Fosbretabulin Paclitaxel Carboplatin (AUC 6), paclitaxel (200 mg/m2), and bevacizumab (15 mg/kg), administered intravenously Day 1 of a 21-day cycle and fosbretabulin (60 mg/m2) on Days 7, 14, and 21 for up to six treatment cycles. After 6 cycles, subjects who have not progressed may continue to receive bevacizumab (15 mg/kg) on Day 1 and fosbretabulin on Days 1, 7 and 14 every 3 weeks until progression or until 12 months from randomization. Arm 2: Active Comparator+Fosbretabulin Bevacizumab Carboplatin (AUC 6), paclitaxel (200 mg/m2), and bevacizumab (15 mg/kg), administered intravenously Day 1 of a 21-day cycle and fosbretabulin (60 mg/m2) on Days 7, 14, and 21 for up to six treatment cycles. After 6 cycles, subjects who have not progressed may continue to receive bevacizumab (15 mg/kg) on Day 1 and fosbretabulin on Days 1, 7 and 14 every 3 weeks until progression or until 12 months from randomization. Arm 2: Active Comparator+Fosbretabulin Fosbretabulin Carboplatin (AUC 6), paclitaxel (200 mg/m2), and bevacizumab (15 mg/kg), administered intravenously Day 1 of a 21-day cycle and fosbretabulin (60 mg/m2) on Days 7, 14, and 21 for up to six treatment cycles. After 6 cycles, subjects who have not progressed may continue to receive bevacizumab (15 mg/kg) on Day 1 and fosbretabulin on Days 1, 7 and 14 every 3 weeks until progression or until 12 months from randomization.
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS) in the Intent-to-Treat Population Six 21-day cycles Progression was defined using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0. Based on 20% increase of the longest diameter of target lesions or appearance of one or more new non-target lesions or/and progression of non-target lesions since the treatment started.
- Secondary Outcome Measures
Name Time Method Best Overall Tumor Response Rate (RR) in the Intent-to-Treat Population Six 21-day cycles Based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0 for target lesions (assessed by MRI or CT scan): Complete Response (CR) is defined as the disappearance of all target lesions, Partial Response (PR) is defined as at least a 30% decrease in the sum of the longest diameter of target lesions, Progressive Disease is defined as at least 20% increase in the sum of the longest diameter of target lesions, Stable Disease (SD) is defined as neither shrinkage to qualify for a PR or increase to qualify for a PD.
Coagulation NCI-CTCAE Grade 3 or 4 (Safety Population) Day 1 (pretreatment) per 21-day Cycle (6 Cycles) Overall Survival (OS) Using a Multivariate Cox Regression Model in the Intent-to-Treat Population Until death or lost to follow-up, up to 12 months since randomization Chemistry NCI-CTCAE Toxicity Grade of 3 or 4 (Safety Population) Days 1 (pretreatment) per 21-day Cycle (6 Cycles) Hematology NCI-CTCAE Grade 3 or 4 (Safety Population) Days 1 (pretreatment), 7, 14, and 21 per 21-day Cycle (6 Cycles)
Trial Locations
- Locations (15)
Pacific Coast Hematology and Oncology Medical Group
🇺🇸Fountain Valley, California, United States
The Mark H. Zangmeister Center
🇺🇸Columbus, Ohio, United States
Southbay Oncology Hematology
🇺🇸Campbell, California, United States
UCLA Division of Hematology and Oncology
🇺🇸Los Angeles, California, United States
Bay Area Cancer Research Group, LLC
🇺🇸Pleasant Hill, California, United States
Boca Raton Comprehensive Cancer Center
🇺🇸Boca Raton, Florida, United States
Gabrail Cancer Center
🇺🇸Canton, Ohio, United States
Lahey Clinic Medical Center
🇺🇸Burlington, Massachusetts, United States
San Juan Oncology Associates
🇺🇸Farmington, New Mexico, United States
The Center for Cancer and Hematologic Disease
🇺🇸Cherry Hill, New Jersey, United States
Signal Point Clinical Research
🇺🇸Middletown, Ohio, United States
Blueridge Cancer Care
🇺🇸Salem, Virginia, United States
Northwest Medical Specialties
🇺🇸Tacoma, Washington, United States
Mary Babb Randolph Cancer Center-Clinical Trials Unit
🇺🇸Morgantown, West Virginia, United States
Kentuckiana Cancer Institute
🇺🇸Louisville, Kentucky, United States