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

Non-small Cell Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00794417
• Other study ID #: VGFT-ST-0708
• Secondary ID: TCD10767
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: November 30, 2008
• Est. completion date: June 30, 2011

Study information

• Verified date: November 2020
• Source: Regeneron Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 60
• Est. completion date: June 30, 2011
• Est. primary completion date: June 30, 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Carcinoma
• Carcinoma
• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

Drug:
• Aflibercept
Administered in combination with the other two interventions via intravenous infusion.
• Pemetrexed
Administered in combination with the other two interventions via intravenous infusion.
• Cisplatin
Administered in combination with the other two interventions via intravenous infusion.

Locations

Country	Name	City	State
Canada	Princess Margaret Hospital	Toronto	Ontario
United States	UNM Cancer Clinic	Albuquerque	New Mexico
United States	Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland
United States	Palm Beach Institute of Hematology and Oncology	Boynton Beach	Florida
United States	Montefiore Medical Center	Bronx	New York
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Presbyterian Hospital Center for Cancer Research	Charlotte	North Carolina
United States	Erie Regional Cancer Center	Erie	Pennsylvania
United States	Kentucky Cancer Clinic	Hazard	Kentucky
United States	Edward Hines Jr. VA Medical Center	Hines	Illinois
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	University of Arkansas for Medical Science	Little Rock	Arkansas
United States	Stanford University Medical Center	Stanford	California
United States	Arizona Cancer Institute, LLC	Tucson	Arizona
United States	Schiffler Cancer Center - Medical Oncology Division	Wheeling	West Virginia

Sponsors (2)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals	Sanofi

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (2)

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 previ — View 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 c — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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: Baseline (Day 421) up to end of study (Day 972)
Secondary	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 2: Baseline (Day 421) up to end of study (Day 972)
Secondary	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: Baseline up to 751 Days; Phase 2: Baseline (Day 421) up to 972 Days
Secondary	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: Pre-dose up to Day 22 post-dose
Secondary	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: Pre-dose up to Day 1 post-dose, Day 2 post-dose (only in Phase 1)
Secondary	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: 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)
Secondary	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: Pre-dose up to Day 22 post-dose
Secondary	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: Pre-dose up to Day 1 post-dose, Day 2 post-dose (only in Phase 1)
Secondary	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: Pre-dose up to Day 22 post-dose
Secondary	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: Pre-dose up to Day 1 post-dose, Day 2 post-dose (only in Phase 1)
Secondary	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: Baseline up to 315 Days; Phase 2: Baseline (Day 421) up to Day 739
Secondary	Phase 1 and 2: Number of Participants With All Grade Glucose Abnormalities		Phase 1: Baseline up to 751 Days; Phase 2: Baseline (Day 421) up to 972 Days
Secondary	Phase 1 and 2: Number of Participants With All Grade Hematology Abnormalities		Phase 1: Baseline up to 751 Days; Phase 2: Baseline (Day 421) up to 972 Days