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A Study of Aflibercept Administered in Combination With Pemetrexed and Cisplatin in Participants With Advanced Carcinoma

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ClinicalTrials.gov Identifier: NCT00794417
Recruitment Status : Terminated
First Posted : November 20, 2008
Results First Posted : December 10, 2020
Last Update Posted : December 10, 2020
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Regeneron Pharmaceuticals

Study Description
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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).

Condition or disease Intervention/treatment Phase
Advanced Carcinoma Non-small Cell Lung Cancer Drug: Aflibercept Drug: Pemetrexed Drug: Cisplatin Phase 1 Phase 2

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
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 60 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Study of Aflibercept Administered in Combination With Pemetrexed and Cisplatin in Patients With Advanced Carcinoma
Actual Study Start Date : November 30, 2008
Actual Primary Completion Date : June 30, 2011
Actual Study Completion Date : June 30, 2011

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: 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.
 Drug: Aflibercept
Administered in combination with the other two interventions via intravenous infusion.

Drug: Pemetrexed
Administered in combination with the other two interventions via intravenous infusion.
Other Name: Alimta

Drug: Cisplatin
Administered in combination with the other two interventions via intravenous infusion.
Other Name: Platinol
Experimental: 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.
 Drug: Aflibercept
Administered in combination with the other two interventions via intravenous infusion.

Drug: Pemetrexed
Administered in combination with the other two interventions via intravenous infusion.
Other Name: Alimta

Drug: Cisplatin
Administered in combination with the other two interventions via intravenous infusion.
Other Name: Platinol
Experimental: 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.
 Drug: Aflibercept
Administered in combination with the other two interventions via intravenous infusion.

Drug: Pemetrexed
Administered in combination with the other two interventions via intravenous infusion.
Other Name: Alimta

Drug: Cisplatin
Administered in combination with the other two interventions via intravenous infusion.
Other Name: Platinol
Experimental: 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.
 Drug: Aflibercept
Administered in combination with the other two interventions via intravenous infusion.

Drug: Pemetrexed
Administered in combination with the other two interventions via intravenous infusion.
Other Name: Alimta

Drug: Cisplatin
Administered in combination with the other two interventions via intravenous infusion.
Other Name: Platinol


Outcome Measures
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Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. Phase 2: Objective Response Rate [ Time Frame: 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.

  2. Phase 2: Progression-free Survival (PFS) [ Time Frame: 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.

  3. Phase 1 and 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) [ Time Frame: 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.

  4. Phase 1 and 2: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Aflibercept [ Time Frame: 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.

  5. Phase 1 and 2: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Pemetrexed [ Time Frame: 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.

  6. Phase 1 and 2: Maximum Observed Plasma Concentration (Cmax) of Aflibercept and Pemetrexed [ Time Frame: 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.

  7. Phase 1 and 2: Total Body Clearance of Aflibercept [ Time Frame: 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.

  8. Phase 1 and 2: Total Body Clearance of Pemetrexed [ Time Frame: 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.

  9. Phase 1 and 2: Terminal Half-Life (t1/2) of Aflibercept [ Time Frame: 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.

  10. Phase 1 and 2: Terminal Half-Life (t1/2) of Pemetrexed [ Time Frame: 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.

  11. Phase 1 and 2: Number of Participants With Positive Anti-drug Antibody (ADA) of Aflibercept [ Time Frame: 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.

  12. Phase 1 and 2: Number of Participants With All Grade Glucose Abnormalities [ Time Frame: Phase 1: Baseline up to 751 Days; Phase 2: Baseline (Day 421) up to 972 Days ]
  13. Phase 1 and 2: Number of Participants With All Grade Hematology Abnormalities [ Time Frame: Phase 1: Baseline up to 751 Days; Phase 2: Baseline (Day 421) up to 972 Days ]

Eligibility Criteria
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Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00794417


Locations
Layout table for location information
United States, Arizona
Arizona Cancer Institute, LLC
Tucson, Arizona, United States, 85715
United States, Arkansas
University of Arkansas for Medical Science
Little Rock, Arkansas, United States, 72205
United States, California
Stanford University Medical Center
Stanford, California, United States, 94305
United States, Florida
Palm Beach Institute of Hematology and Oncology
Boynton Beach, Florida, United States, 33435
United States, Illinois
Edward Hines Jr. VA Medical Center
Hines, Illinois, United States, 60141
United States, Kentucky
Kentucky Cancer Clinic
Hazard, Kentucky, United States, 41701
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States, 21231-1000
United States, New Hampshire
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756
United States, New Mexico
UNM Cancer Clinic
Albuquerque, New Mexico, United States, 87131
United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10467
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
United States, North Carolina
Presbyterian Hospital Center for Cancer Research
Charlotte, North Carolina, United States, 28204
United States, Pennsylvania
Erie Regional Cancer Center
Erie, Pennsylvania, United States, 16505
United States, West Virginia
Schiffler Cancer Center - Medical Oncology Division
Wheeling, West Virginia, United States, 26003
Canada, Ontario
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
Regeneron Pharmaceuticals
Sanofi
Investigators
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Study Director: Clinical Trial Management Regeneron Pharmaceuticals
More Information
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Publications of Results:

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Responsible Party: Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00794417    
Other Study ID Numbers: VGFT-ST-0708
TCD10767
First Posted: November 20, 2008    Key Record Dates
Results First Posted: December 10, 2020
Last Update Posted: December 10, 2020
Last Verified: November 2020
Keywords provided by Regeneron Pharmaceuticals:
advanced cancer
lung cancer
NSCLC
 Non-small Cell Lung Cancer
aflibercept
chemotherapy
Additional relevant MeSH terms:
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Carcinoma
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
 Pemetrexed
Aflibercept
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors