search
Back to results

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

Primary Purpose

Advanced Carcinoma, Non-small Cell Lung Cancer

Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Aflibercept
Pemetrexed
Cisplatin
Sponsored by
Regeneron Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Carcinoma focused on measuring advanced cancer, lung cancer, NSCLC, Non-small Cell Lung Cancer, aflibercept, chemotherapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Arizona Cancer Institute, LLC
  • University of Arkansas for Medical Science
  • Stanford University Medical Center
  • Palm Beach Institute of Hematology and Oncology
  • Edward Hines Jr. VA Medical Center
  • Kentucky Cancer Clinic
  • Sidney Kimmel Comprehensive Cancer Center
  • Dartmouth-Hitchcock Medical Center
  • UNM Cancer Clinic
  • Montefiore Medical Center
  • Roswell Park Cancer Institute
  • Presbyterian Hospital Center for Cancer Research
  • Erie Regional Cancer Center
  • Schiffler Cancer Center - Medical Oncology Division
  • Princess Margaret Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Phase 1: Aflibercept 6 mg/kg and Pemetrexed and Cisplatin

Phase 1: Aflibercept 2 mg/kg and Pemetrexed and Cisplatin

Phase 1: Aflibercept 4 mg/kg and Pemetrexed and Cisplatin

Phase 2: Aflibercept 6 mg/kg and Pemetrexed and Cisplatin

Arm Description

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Phase 2: Objective Response Rate
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: Progression-free Survival (PFS)
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 1 and 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
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 and 2: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Aflibercept
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: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Pemetrexed
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: Maximum Observed Plasma Concentration (Cmax) of Aflibercept and Pemetrexed
Cmax is the maximum observed plasma concentration obtained directly from the concentration versus time curve.
Phase 1 and 2: Total Body Clearance of Aflibercept
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: Total Body Clearance of Pemetrexed
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: Terminal Half-Life (t1/2) of Aflibercept
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: Terminal Half-Life (t1/2) of Pemetrexed
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: Number of Participants With Positive Anti-drug Antibody (ADA) of Aflibercept
Serum samples were analyzed by a validated electrochemiluminescence immunoassay to detect the presence of ADA.
Phase 1 and 2: Number of Participants With All Grade Glucose Abnormalities
Phase 1 and 2: Number of Participants With All Grade Hematology Abnormalities

Full Information

First Posted
November 19, 2008
Last Updated
November 13, 2020
Sponsor
Regeneron Pharmaceuticals
Collaborators
Sanofi
search

1. Study Identification

Unique Protocol Identification Number
NCT00794417
Brief Title
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

2. Study Status

Record Verification Date
November 2020
Overall Recruitment Status
Terminated
Study Start Date
November 30, 2008 (Actual)
Primary Completion Date
June 30, 2011 (Actual)
Study Completion Date
June 30, 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Regeneron Pharmaceuticals
Collaborators
Sanofi

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Carcinoma, Non-small Cell Lung Cancer
Keywords
advanced cancer, lung cancer, NSCLC, Non-small Cell Lung Cancer, aflibercept, chemotherapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
60 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Phase 1: Aflibercept 6 mg/kg and Pemetrexed and Cisplatin
Arm Type
Experimental
Arm Description
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.
Arm Title
Phase 1: Aflibercept 2 mg/kg and Pemetrexed and Cisplatin
Arm Type
Experimental
Arm Description
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.
Arm Title
Phase 1: Aflibercept 4 mg/kg and Pemetrexed and Cisplatin
Arm Type
Experimental
Arm Description
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.
Arm Title
Phase 2: Aflibercept 6 mg/kg and Pemetrexed and Cisplatin
Arm Type
Experimental
Arm Description
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 Type
Drug
Intervention Name(s)
Aflibercept
Intervention Description
Administered in combination with the other two interventions via intravenous infusion.
Intervention Type
Drug
Intervention Name(s)
Pemetrexed
Other Intervention Name(s)
Alimta
Intervention Description
Administered in combination with the other two interventions via intravenous infusion.
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Other Intervention Name(s)
Platinol
Intervention Description
Administered in combination with the other two interventions via intravenous infusion.
Primary Outcome Measure Information:
Title
Phase 1: Recommended Dose of Aflibercept for Phase 2
Description
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.
Time Frame
Phase 1: Baseline up to 315 Days
Secondary Outcome Measure Information:
Title
Phase 2: Objective Response Rate
Description
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.
Time Frame
Phase 2: Baseline (Day 421) up to end of study (Day 972)
Title
Phase 2: Progression-free Survival (PFS)
Description
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.
Time Frame
Phase 2: Baseline (Day 421) up to end of study (Day 972)
Title
Phase 1 and 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Description
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.
Time Frame
Phase 1: Baseline up to 751 Days; Phase 2: Baseline (Day 421) up to 972 Days
Title
Phase 1 and 2: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Aflibercept
Description
The AUC0-inf was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity.
Time Frame
Phase 1 and 2: Pre-dose up to Day 22 post-dose
Title
Phase 1 and 2: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Pemetrexed
Description
The AUC0-inf was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity.
Time Frame
Phase 1 and 2: Pre-dose up to Day 1 post-dose, Day 2 post-dose (only in Phase 1)
Title
Phase 1 and 2: Maximum Observed Plasma Concentration (Cmax) of Aflibercept and Pemetrexed
Description
Cmax is the maximum observed plasma concentration obtained directly from the concentration versus time curve.
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)
Title
Phase 1 and 2: Total Body Clearance of Aflibercept
Description
Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Time Frame
Phase 1 and 2: Pre-dose up to Day 22 post-dose
Title
Phase 1 and 2: Total Body Clearance of Pemetrexed
Description
Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Time Frame
Phase 1 and 2: Pre-dose up to Day 1 post-dose, Day 2 post-dose (only in Phase 1)
Title
Phase 1 and 2: Terminal Half-Life (t1/2) of Aflibercept
Description
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.
Time Frame
Phase 1 and 2: Pre-dose up to Day 22 post-dose
Title
Phase 1 and 2: Terminal Half-Life (t1/2) of Pemetrexed
Description
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.
Time Frame
Phase 1 and 2: Pre-dose up to Day 1 post-dose, Day 2 post-dose (only in Phase 1)
Title
Phase 1 and 2: Number of Participants With Positive Anti-drug Antibody (ADA) of Aflibercept
Description
Serum samples were analyzed by a validated electrochemiluminescence immunoassay to detect the presence of ADA.
Time Frame
Phase 1: Baseline up to 315 Days; Phase 2: Baseline (Day 421) up to Day 739
Title
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
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trial Management
Organizational Affiliation
Regeneron Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Arizona Cancer Institute, LLC
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85715
Country
United States
Facility Name
University of Arkansas for Medical Science
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
Facility Name
Stanford University Medical Center
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Palm Beach Institute of Hematology and Oncology
City
Boynton Beach
State/Province
Florida
ZIP/Postal Code
33435
Country
United States
Facility Name
Edward Hines Jr. VA Medical Center
City
Hines
State/Province
Illinois
ZIP/Postal Code
60141
Country
United States
Facility Name
Kentucky Cancer Clinic
City
Hazard
State/Province
Kentucky
ZIP/Postal Code
41701
Country
United States
Facility Name
Sidney Kimmel Comprehensive Cancer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231-1000
Country
United States
Facility Name
Dartmouth-Hitchcock Medical Center
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756
Country
United States
Facility Name
UNM Cancer Clinic
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87131
Country
United States
Facility Name
Montefiore Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Facility Name
Presbyterian Hospital Center for Cancer Research
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Facility Name
Erie Regional Cancer Center
City
Erie
State/Province
Pennsylvania
ZIP/Postal Code
16505
Country
United States
Facility Name
Schiffler Cancer Center - Medical Oncology Division
City
Wheeling
State/Province
West Virginia
ZIP/Postal Code
26003
Country
United States
Facility Name
Princess Margaret Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
22805331
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.
Results Reference
result
PubMed Identifier
24292447
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.
Results Reference
result

Learn more about this trial

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

We'll reach out to this number within 24 hrs