A Study of Aflibercept Administered in Combination With Pemetrexed and Cisplatin in Participants With Advanced Carcinoma
A Phase 1/2 Study of Aflibercept Administered in Combination With Pemetrexed and Cisplatin in Patients With Advanced Carcinoma
2 other identifiers
interventional
60
2 countries
15
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Nov 2008
Typical duration for phase_1
15 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 19, 2008
CompletedFirst Posted
Study publicly available on registry
November 20, 2008
CompletedStudy Start
First participant enrolled
November 30, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 30, 2011
CompletedStudy Completion
Last participant's last visit for all outcomes
June 30, 2011
CompletedResults Posted
Study results publicly available
December 10, 2020
CompletedDecember 10, 2020
November 1, 2020
2.6 years
November 19, 2008
September 25, 2020
November 13, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Phase 1: Recommended Dose of Aflibercept for Phase 2
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.
Phase 1: Baseline up to 315 Days
Secondary Outcomes (13)
Phase 2: Objective Response Rate
Phase 2: Baseline (Day 421) up to end of study (Day 972)
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 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: 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: 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)
- +8 more secondary outcomes
Study Arms (4)
Phase 1: Aflibercept 6 mg/kg and Pemetrexed and Cisplatin
EXPERIMENTALParticipants 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 2 mg/kg and Pemetrexed and Cisplatin
EXPERIMENTALParticipants 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
EXPERIMENTALParticipants 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
EXPERIMENTALParticipants 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.
Interventions
Administered in combination with the other two interventions via intravenous infusion.
Administered in combination with the other two interventions via intravenous infusion.
Administered in combination with the other two interventions via intravenous infusion.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Regeneron Pharmaceuticalslead
- Sanoficollaborator
Study Sites (15)
Arizona Cancer Institute, LLC
Tucson, Arizona, 85715, United States
University of Arkansas for Medical Science
Little Rock, Arkansas, 72205, United States
Stanford University Medical Center
Stanford, California, 94305, United States
Palm Beach Institute of Hematology and Oncology
Boynton Beach, Florida, 33435, United States
Edward Hines Jr. VA Medical Center
Hines, Illinois, 60141, United States
Kentucky Cancer Clinic
Hazard, Kentucky, 41701, United States
Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, 21231-1000, United States
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03756, United States
UNM Cancer Clinic
Albuquerque, New Mexico, 87131, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
Montefiore Medical Center
The Bronx, New York, 10467, United States
Presbyterian Hospital Center for Cancer Research
Charlotte, North Carolina, 28204, United States
Erie Regional Cancer Center
Erie, Pennsylvania, 16505, United States
Schiffler Cancer Center - Medical Oncology Division
Wheeling, West Virginia, 26003, United States
Princess Margaret Hospital
Toronto, Ontario, M5G 2M9, Canada
Related Publications (2)
Diaz-Padilla I, Siu LL, San Pedro-Salcedo M, Razak AR, Colevas AD, Shepherd FA, Leighl NB, Neal JW, Thibault A, Liu L, Lisano J, Gao B, Lawson EB, Wakelee HA. A phase I dose-escalation study of aflibercept administered in combination with pemetrexed and cisplatin in patients with advanced solid tumours. Br J Cancer. 2012 Aug 7;107(4):604-11. doi: 10.1038/bjc.2012.319. Epub 2012 Jul 17.
PMID: 22805331RESULTChen H, Modiano MR, Neal JW, Brahmer JR, Rigas JR, Jotte RM, Leighl NB, Riess JW, Kuo CJ, Liu L, Gao B, Dicioccio AT, Adjei AA, Wakelee HA. A phase II multicentre study of ziv-aflibercept in combination with cisplatin and pemetrexed in patients with previously untreated advanced/metastatic non-squamous non-small cell lung cancer. Br J Cancer. 2014 Feb 4;110(3):602-8. doi: 10.1038/bjc.2013.735. Epub 2013 Nov 28.
PMID: 24292447RESULT
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Clinical Trial Administrator
- Organization
- Regeneron Pharmaceuticals, Inc.
Study Officials
- STUDY DIRECTOR
Clinical Trial Management
Regeneron Pharmaceuticals
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 19, 2008
First Posted
November 20, 2008
Study Start
November 30, 2008
Primary Completion
June 30, 2011
Study Completion
June 30, 2011
Last Updated
December 10, 2020
Results First Posted
December 10, 2020
Record last verified: 2020-11