A Phase 1/2 Study of Aflibercept Administered in Combination With Pemetrexed and Cisplatin in Patients With Advanced Carcinoma
Trial Snapshot
- Phase
- Phase 1
- Status
- Terminated
- Sponsor
- Regeneron Pharmaceuticals
- Enrollment
- 60
- Locations
- 15
- Primary Endpoint
- Phase 1: Recommended Dose of Aflibercept for Phase 2
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
Exclusion Criteria
- •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
Arms & Interventions
Phase 1: Aflibercept 6 mg/kg and Pemetrexed and 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.
Intervention: Aflibercept (Drug)
Phase 1: Aflibercept 6 mg/kg and Pemetrexed and 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.
Intervention: Pemetrexed (Drug)
Phase 1: Aflibercept 6 mg/kg and Pemetrexed and 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.
Intervention: Cisplatin (Drug)
Phase 1: Aflibercept 2 mg/kg and Pemetrexed and 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.
Intervention: Aflibercept (Drug)
Phase 1: Aflibercept 2 mg/kg and Pemetrexed and 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.
Intervention: Pemetrexed (Drug)
Phase 1: Aflibercept 2 mg/kg and Pemetrexed and 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.
Intervention: Cisplatin (Drug)
Phase 1: Aflibercept 4 mg/kg and Pemetrexed and 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.
Intervention: Aflibercept (Drug)
Phase 1: Aflibercept 4 mg/kg and Pemetrexed and 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.
Intervention: Pemetrexed (Drug)
Phase 1: Aflibercept 4 mg/kg and Pemetrexed and 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.
Intervention: Cisplatin (Drug)
Phase 2: Aflibercept 6 mg/kg and Pemetrexed and 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.
Intervention: Aflibercept (Drug)
Phase 2: Aflibercept 6 mg/kg and Pemetrexed and 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.
Intervention: Pemetrexed (Drug)
Phase 2: Aflibercept 6 mg/kg and Pemetrexed and 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.
Intervention: Cisplatin (Drug)
Outcomes
Primary Outcomes
Phase 1: Recommended Dose of Aflibercept for Phase 2
Time Frame: 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 Outcomes
- Phase 2: Progression-free Survival (PFS)(Phase 2: Baseline (Day 421) up to end of study (Day 972))
- 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)
- 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)
- 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))
- Phase 1 and 2: Terminal Half-Life (t1/2) of Aflibercept(Phase 1 and 2: Pre-dose up to Day 22 post-dose)
- Phase 2: Objective Response Rate(Phase 2: Baseline (Day 421) up to end of study (Day 972))
- 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)
- 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))
- Phase 1 and 2: Total Body Clearance of Aflibercept(Phase 1 and 2: Pre-dose up to Day 22 post-dose)
- 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))
- 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))