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

November 13, 2020 updated by: Regeneron Pharmaceuticals

A Phase 1/2 Study of Aflibercept Administered in Combination With Pemetrexed and Cisplatin in Patients With Advanced Carcinoma

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
60

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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 Names:
  • Alimta
Drug: Cisplatin
Administered in combination with the other two interventions via intravenous infusion.
Other Names:
  • 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 Names:
  • Alimta
Drug: Cisplatin
Administered in combination with the other two interventions via intravenous infusion.
Other Names:
  • 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 Names:
  • Alimta
Drug: Cisplatin
Administered in combination with the other two interventions via intravenous infusion.
Other Names:
  • 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 Names:
  • Alimta
Drug: Cisplatin
Administered in combination with the other two interventions via intravenous infusion.
Other Names:
  • Platinol

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
Phase 1: Baseline up to 315 Days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
Phase 2: Baseline (Day 421) up to end of study (Day 972)
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.
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)
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.
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
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.
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
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.
Phase 1 and 2: Pre-dose up to Day 1 post-dose, Day 2 post-dose (only in Phase 1)
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.
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
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.
Phase 1 and 2: Pre-dose up to Day 22 post-dose
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.
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
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.
Phase 1 and 2: Pre-dose up to Day 22 post-dose
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.
Phase 1 and 2: Pre-dose up to Day 1 post-dose, Day 2 post-dose (only in Phase 1)
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.
Phase 1: Baseline up to 315 Days; Phase 2: Baseline (Day 421) up to Day 739
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
Phase 1: Baseline up to 751 Days; Phase 2: Baseline (Day 421) up to 972 Days
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
Phase 1: Baseline up to 751 Days; Phase 2: Baseline (Day 421) up to 972 Days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Regeneron Pharmaceuticals

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Sanofi

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 30, 2008

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 30, 2011

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 30, 2011

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 19, 2008

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 19, 2008

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 20, 2008

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 10, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 13, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • VGFT-ST-0708
  • TCD10767

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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