Clinical trial NCT00794417: A Study of Aflibercept Administered in Combination With Pemetrexed and Cisplatin in Participants With Advanced Carcinoma
Official title: A Phase 1/2 Study of Aflibercept Administered in Combination With Pemetrexed and Cisplatin in Patients With Advanced Carcinoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Advanced Carcinoma
Non-small Cell Lung Cancer
Keywords: advanced cancer
lung cancer
NSCLC
Non-small Cell Lung Cancer
aflibercept
chemotherapy
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2008-11-20
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Phase 1: Recommended Dose of Aflibercept for Phase 2
timeFrame: Phase 1: Baseline up to 315 Days
Secondary outcomes:
measure: Phase 2: Objective Response Rate
timeFrame: Phase 2: Baseline (Day 421) up to end of study (Day 972)
measure: Phase 2: Progression-free Survival (PFS)
timeFrame: Phase 2: Baseline (Day 421) up to end of study (Day 972)
measure: Phase 1 and 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
timeFrame: Phase 1: Baseline up to 751 Days; Phase 2: Baseline (Day 421) up to 972 Days
measure: Phase 1 and 2: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Aflibercept
timeFrame: Phase 1 and 2: Pre-dose up to Day 22 post-dose
measure: Phase 1 and 2: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Pemetrexed
timeFrame: Phase 1 and 2: Pre-dose up to Day 1 post-dose, Day 2 post-dose (only in Phase 1)
measure: Phase 1 and 2: Maximum Observed Plasma Concentration (Cmax) of Aflibercept and Pemetrexed
timeFrame: 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)
measure: Phase 1 and 2: Total Body Clearance of Aflibercept
timeFrame: Phase 1 and 2: Pre-dose up to Day 22 post-dose
measure: Phase 1 and 2: Total Body Clearance of Pemetrexed
timeFrame: Phase 1 and 2: Pre-dose up to Day 1 post-dose, Day 2 post-dose (only in Phase 1)
measure: Phase 1 and 2: Terminal Half-Life (t1/2) of Aflibercept
timeFrame: Phase 1 and 2: Pre-dose up to Day 22 post-dose
measure: Phase 1 and 2: Terminal Half-Life (t1/2) of Pemetrexed
timeFrame: Phase 1 and 2: Pre-dose up to Day 1 post-dose, Day 2 post-dose (only in Phase 1)
measure: Phase 1 and 2: Number of Participants With Positive Anti-drug Antibody (ADA) of Aflibercept
timeFrame: Phase 1: Baseline up to 315 Days; Phase 2: Baseline (Day 421) up to Day 739
measure: Phase 1 and 2: Number of Participants With All Grade Glucose Abnormalities
timeFrame: Phase 1: Baseline up to 751 Days; Phase 2: Baseline (Day 421) up to 972 Days
measure: Phase 1 and 2: Number of Participants With All Grade Hematology Abnormalities
timeFrame: Phase 1: Baseline up to 751 Days; Phase 2: Baseline (Day 421) up to 972 Days
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Cancer Institute, LLC
state: Arizona
city: Little Rock
country: United States
facility: University of Arkansas for Medical Science
state: Arkansas
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Boynton Beach
country: United States
facility: Palm Beach Institute of Hematology and Oncology
state: Florida
city: Hines
country: United States
facility: Edward Hines Jr. VA Medical Center
state: Illinois
city: Hazard
country: United States
facility: Kentucky Cancer Clinic
state: Kentucky
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center
state: Maryland
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Albuquerque
country: United States
facility: UNM Cancer Clinic
state: New Mexico
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Charlotte
country: United States
facility: Presbyterian Hospital Center for Cancer Research
state: North Carolina
city: Erie
country: United States
facility: Erie Regional Cancer Center
state: Pennsylvania
city: Wheeling
country: United States
facility: Schiffler Cancer Center - Medical Oncology Division
state: West Virginia
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Chen 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.