A Study of Aflibercept Administered in Combination With Pemetrexed and Cisplatin in Participants With Advanced Carcinoma
- Conditions
- Advanced CarcinomaNon-small Cell Lung Cancer
- Interventions
- Registration Number
- NCT00794417
- Lead Sponsor
- Regeneron Pharmaceuticals
- Brief Summary
The purpose of the study was to determine whether the combination of aflibercept, pemetrexed and cisplatin is safe and effective in treating non-small cell lung cancer (NSCLC).
- Detailed Description
The study was conducted in two phases. In phase 1, patients with advanced cancer received different doses of aflibercept in combination with approved doses of pemetrexed and cisplatin. The objective of phase 1 was to determine the safest dose of the combined study medications. This dose was administered to patients with previously untreated NSCLC in phase 2. The phase 2 portion of the study determined if the combination is effective in treating NSCLC.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 60
- Confirmation of cancer by biopsy (tissue sample)
- Phase 1: patients with advanced or metastatic disease that have failed conventional therapy
- Phase 2: patients with previously untreated NSCLC, excluding squamous cell histology and cavitating lesions
- Age ≥18 years
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Adequate renal, liver and bone marrow function.
- Negative pregnancy test (serum or urine) in females of childbearing potential within 7 days of the initial dose of aflibercept
- Ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
- Institutional Review Board (IRB) approved, signed and dated informed consent form
-
Prior treatment with study medications
-
Untreated, symptomatic, or progressive Central Nervous System cancer and/or spinal cord compression. Patients with treated brain metastases must have been without symptoms for at least 3 months
-
Surgery up to 4 weeks prior to the initial administration of aflibercept and/or incomplete wound healing
-
Anti-VEGF therapy up to 4 weeks prior to the initial administration of aflibercept (for phase 1 only)
-
Chemotherapy up to 4 weeks prior to the initial administration of aflibercept (for phase 1 only)
-
Other investigational treatment up to 4 weeks prior to the initial administration of aflibercept
-
Any of the following up to 6 months (24 weeks) prior to the initial administration of aflibercept:
- Severe cardiovascular disease or event
- Cerebrovascular accident, transient ischemic attack, or moderate to severe peripheral neuropathy
- Erosive esophagitis or gastritis, infectious or inflammatory bowel disease, and diverticulitis
- Deep vein thrombosis, pulmonary embolism, or other clotting event
- Episode(s)of moderate to severe, continuous bleeding
-
Breast-feeding or pregnancy
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Phase 1: Aflibercept 6 mg/kg and Pemetrexed and Cisplatin Aflibercept Participants received intravenous infusion of aflibercept 6 mg/kg followed by pemetrexed 500 mg/m\^2 and then cisplatin 75 mg/m\^2 on Day 1 of each 3 week cycle (1 Cycle = 21 Days in this study) until disease progression, unacceptable toxicity, withdrawal of consent or if another study withdrawal criterion has been met. Phase 1: Aflibercept 6 mg/kg and Pemetrexed and Cisplatin Pemetrexed Participants received intravenous infusion of aflibercept 6 mg/kg followed by pemetrexed 500 mg/m\^2 and then cisplatin 75 mg/m\^2 on Day 1 of each 3 week cycle (1 Cycle = 21 Days in this study) until disease progression, unacceptable toxicity, withdrawal of consent or if another study withdrawal criterion has been met. Phase 1: Aflibercept 4 mg/kg and Pemetrexed and Cisplatin Aflibercept Participants received intravenous infusion of aflibercept 4 mg/kg followed by pemetrexed 500 mg/m\^2 and then cisplatin 75 mg/m\^2 on Day 1 of each 3 week cycle (1 Cycle = 21 Days in this study) until disease progression, unacceptable toxicity, withdrawal of consent or if another study withdrawal criterion has been met. Phase 1: Aflibercept 6 mg/kg and Pemetrexed and Cisplatin Cisplatin Participants received intravenous infusion of aflibercept 6 mg/kg followed by pemetrexed 500 mg/m\^2 and then cisplatin 75 mg/m\^2 on Day 1 of each 3 week cycle (1 Cycle = 21 Days in this study) until disease progression, unacceptable toxicity, withdrawal of consent or if another study withdrawal criterion has been met. Phase 2: Aflibercept 6 mg/kg and Pemetrexed and Cisplatin Cisplatin Participants received intravenous infusion of aflibercept 6 mg/kg followed by pemetrexed 500 mg/m\^2 and then cisplatin 75 mg/m\^2 on Day 1 of each 3 week cycle (1 Cycle = 21 Days in this study) for 6 cycles. Phase 1: Aflibercept 2 mg/kg and Pemetrexed and Cisplatin Aflibercept Participants received intravenous infusion of aflibercept 2 milligrams per kilogram (mg/kg) followed by pemetrexed 500 mg/square meter (m\^2) and then cisplatin 75 mg/m\^2 on Day 1 of each 3 week cycle (1 Cycle = 21 Days in this study) until disease progression, unacceptable toxicity, withdrawal of consent or if another study withdrawal criterion has been met. Phase 1: Aflibercept 2 mg/kg and Pemetrexed and Cisplatin Pemetrexed Participants received intravenous infusion of aflibercept 2 milligrams per kilogram (mg/kg) followed by pemetrexed 500 mg/square meter (m\^2) and then cisplatin 75 mg/m\^2 on Day 1 of each 3 week cycle (1 Cycle = 21 Days in this study) until disease progression, unacceptable toxicity, withdrawal of consent or if another study withdrawal criterion has been met. Phase 1: Aflibercept 2 mg/kg and Pemetrexed and Cisplatin Cisplatin Participants received intravenous infusion of aflibercept 2 milligrams per kilogram (mg/kg) followed by pemetrexed 500 mg/square meter (m\^2) and then cisplatin 75 mg/m\^2 on Day 1 of each 3 week cycle (1 Cycle = 21 Days in this study) until disease progression, unacceptable toxicity, withdrawal of consent or if another study withdrawal criterion has been met. Phase 1: Aflibercept 4 mg/kg and Pemetrexed and Cisplatin Cisplatin Participants received intravenous infusion of aflibercept 4 mg/kg followed by pemetrexed 500 mg/m\^2 and then cisplatin 75 mg/m\^2 on Day 1 of each 3 week cycle (1 Cycle = 21 Days in this study) until disease progression, unacceptable toxicity, withdrawal of consent or if another study withdrawal criterion has been met. Phase 1: Aflibercept 4 mg/kg and Pemetrexed and Cisplatin Pemetrexed Participants received intravenous infusion of aflibercept 4 mg/kg followed by pemetrexed 500 mg/m\^2 and then cisplatin 75 mg/m\^2 on Day 1 of each 3 week cycle (1 Cycle = 21 Days in this study) until disease progression, unacceptable toxicity, withdrawal of consent or if another study withdrawal criterion has been met. Phase 2: Aflibercept 6 mg/kg and Pemetrexed and Cisplatin Aflibercept Participants received intravenous infusion of aflibercept 6 mg/kg followed by pemetrexed 500 mg/m\^2 and then cisplatin 75 mg/m\^2 on Day 1 of each 3 week cycle (1 Cycle = 21 Days in this study) for 6 cycles. Phase 2: Aflibercept 6 mg/kg and Pemetrexed and Cisplatin Pemetrexed Participants received intravenous infusion of aflibercept 6 mg/kg followed by pemetrexed 500 mg/m\^2 and then cisplatin 75 mg/m\^2 on Day 1 of each 3 week cycle (1 Cycle = 21 Days in this study) for 6 cycles.
- Primary Outcome Measures
Name Time Method Phase 1: Recommended Dose of Aflibercept for Phase 2 Phase 1: Baseline up to 315 Days Recommended Dose was defined as the highest combination dose at which fewer than 33 percent (%) of participants experienced dose limiting toxicity during the first cycle of therapy.
- Secondary Outcome Measures
Name Time Method Phase 2: Progression-free Survival (PFS) Phase 2: Baseline (Day 421) up to end of study (Day 972) PFS was defined as the time in days from the date of first study drug administration to the date of first documentation of tumor progression or death from any cause, whichever occurs first, as assessed by the modified RECIST. Median time of PFS was estimated using Kaplan-Meier method.
Phase 1 and 2: Number of Participants With All Grade Glucose Abnormalities Phase 1: Baseline up to 751 Days; Phase 2: Baseline (Day 421) up to 972 Days Phase 1 and 2: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Aflibercept Phase 1 and 2: Pre-dose up to Day 22 post-dose The AUC0-inf was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity.
Phase 1 and 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) Phase 1: Baseline up to 751 Days; Phase 2: Baseline (Day 421) up to 972 Days An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (for example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) was defined as an adverse event with an onset that occurs after receiving study drug. Any TEAE included participants with both serious and non-serious AEs.
Phase 1 and 2: Total Body Clearance of Pemetrexed Phase 1 and 2: Pre-dose up to Day 1 post-dose, Day 2 post-dose (only in Phase 1) Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Phase 1 and 2: Terminal Half-Life (t1/2) of Aflibercept Phase 1 and 2: Pre-dose up to Day 22 post-dose Terminal half-life was defined as the time required for the plasma concentration of drug to decrease 50 percent in the final stage of its elimination.
Phase 2: Objective Response Rate Phase 2: Baseline (Day 421) up to end of study (Day 972) Objective response rate was defined as the percentage of participants who achieved complete response (CR) or partial response (PR) as assessed by modified Response Evaluation Criteria in Solid Tumors (RECIST). CR was defined as disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking the Baseline sum LD as reference.
Phase 1 and 2: Number of Participants With Positive Anti-drug Antibody (ADA) of Aflibercept Phase 1: Baseline up to 315 Days; Phase 2: Baseline (Day 421) up to Day 739 Serum samples were analyzed by a validated electrochemiluminescence immunoassay to detect the presence of ADA.
Phase 1 and 2: Maximum Observed Plasma Concentration (Cmax) of Aflibercept and Pemetrexed Phase 1 and 2: Aflibercept: Pre-dose up to Day 22 post-dose; Pemetrexed: Pre-dose up to Day 1 post-dose, Day 2 post-dose (only in Phase 1) Cmax is the maximum observed plasma concentration obtained directly from the concentration versus time curve.
Phase 1 and 2: Total Body Clearance of Aflibercept Phase 1 and 2: Pre-dose up to Day 22 post-dose Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Phase 1 and 2: Number of Participants With All Grade Hematology Abnormalities Phase 1: Baseline up to 751 Days; Phase 2: Baseline (Day 421) up to 972 Days Phase 1 and 2: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Pemetrexed Phase 1 and 2: Pre-dose up to Day 1 post-dose, Day 2 post-dose (only in Phase 1) The AUC0-inf was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity.
Phase 1 and 2: Terminal Half-Life (t1/2) of Pemetrexed Phase 1 and 2: Pre-dose up to Day 1 post-dose, Day 2 post-dose (only in Phase 1) Terminal half-life was defined as the time required for the plasma concentration of drug to decrease 50 percent in the final stage of its elimination.
Trial Locations
- Locations (15)
Stanford University Medical Center
🇺🇸Stanford, California, United States
Palm Beach Institute of Hematology and Oncology
🇺🇸Boynton Beach, Florida, United States
Kentucky Cancer Clinic
🇺🇸Hazard, Kentucky, United States
Sidney Kimmel Comprehensive Cancer Center
🇺🇸Baltimore, Maryland, United States
Dartmouth-Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
UNM Cancer Clinic
🇺🇸Albuquerque, New Mexico, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Presbyterian Hospital Center for Cancer Research
🇺🇸Charlotte, North Carolina, United States
Erie Regional Cancer Center
🇺🇸Erie, Pennsylvania, United States
Princess Margaret Hospital
🇨🇦Toronto, Ontario, Canada
Arizona Cancer Institute, LLC
🇺🇸Tucson, Arizona, United States
Schiffler Cancer Center - Medical Oncology Division
🇺🇸Wheeling, West Virginia, United States
University of Arkansas for Medical Science
🇺🇸Little Rock, Arkansas, United States
Edward Hines Jr. VA Medical Center
🇺🇸Hines, Illinois, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States