RATIONALE: Monoclonal antibodies, such as ramucirumab and anti-PDGFR alpha monoclonal antibody IMC-3G3 (Olaratumab), can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. PURPOSE: This phase II trial is studying how well ramucirumab or anti-PDGFR alpha monoclonal antibody IMC-3G3 works in treating patients with recurrent glioblastoma multiforme.
OBJECTIVES: Primary * To assess the progression-free survival rate at 6 months after treatment with ramucirumab or anti-PDGFR alpha monoclonal antibody IMC-3G3 in patients with recurrent glioblastoma multiforme. Secondary * To evaluate the acute and late toxicities associated with these regimens. * To assess the objective tumor response rate. * To estimate the overall survival of these patients. * To describe the pharmacokinetic and pharmacodynamic profiles and immunogenicity of these regimens. OUTLINE: This is a multicenter study. Patients are sequentially assigned to 1 of 2 treatment groups. * Group 1: Patients receive ramucirumab IV over 1 hour on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. * Group 2: Patients receive anti-PDGFR alpha monoclonal antibody IMC-3G3 IV over 60-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
80
Given IV
Given IV
UAB Comprehensive Cancer Center
Birmingham, Alabama, United States
Jonsson Comprehensive Cancer Center at UCLA
Los Angeles, California, United States
University of California San Francisco Medical Center
San Francisco, California, United States
H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
Tampa, Florida, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Josephine Ford Cancer Center at Henry Ford Hospital
Detroit, Michigan, United States
Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, United States
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States
University of Pittsburgh School of Medicine
Pittsburgh, Pennsylvania, United States
...and 1 more locations
Percentage of Participants Who Achieved Progression-Free Survival Rate at 6 Months (PFS-6)
PFS was defined as the start of treatment to the earliest date of tumor progression or death from any cause based on the modified Response Assessment in Neuro-Oncology Group through the American Society of Clinical Oncology (RANO) criteria. Progression is defined by any of the following: ≥ 25% increase in sum of the products of perpendicular diameters of enhancing lesions; any new lesion; or clinical deterioration. RANO is a standardized response criteria using bi-dimensional measurements of the largest contrast-enhancing area (Macdonald, 1990).
Time frame: Start of treatment to PD or Death Up To 6 Months
Number of Participants With Treatment Emergent Adverse Events as Assessed by NCI CTCAE v4.0 (National Cancer Institute-Common Terminology Criteria for Adverse Events)
The number of participants who experienced serious adverse events (SAEs) that were considered to be related to ramucirumab or olaratumab. A summary of other non-serious adverse events and all serious adverse events, regardless of causality, is located in the Reported Adverse Events Section.
Time frame: Start of Treatment to End of Study (Up to 13 Months)
Percentage of Participants (Pts) With Complete Response (CR), Partial Response (PR) and Minor Response (MR) (Objective Response Rate [ORR])
The pts achievement of both measurement and confirmation criteria for a status of CR, PR or MR based on the modified RANO criteria.CR requires all of the following:complete disappearance of all enhancing measurable and non-measurable disease sustained for at least 4 weeks (wks);no new lesions;no corticosteroids;and stable or improved clinically.PR requires all of the following:≥ 50% decrease compared with baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions sustained for at least 4 wks;no new lesions;stable or reduced corticosteroid dose;and stable or improved clinically.MR requires ≥ 25% reduction in sum of products of the perpendicular diameters of all measureable enhancing lesions sustained for at least 4 wks and no new lesions or progression of non-measurable lesions. PD is defined by any of these: ≥ 25% increase in sum of the products of perpendicular diameters of enhancing lesions;any new lesion;or clinical deterioration.
Time frame: Start of Treatment to PD Up To 20 Months
Median Overall Survival (OS)
OS is the time from the start of treatment to the date of death. Participants who had not expired by the data analysis cutoff date were censored at their last date known to be alive.
Time frame: Start of Treatment to Death Up To 27 Months
Pharmacokinetics (PK): Concentration Maximum (Cmax) and Concentration Minimum (Cmin) of Ramucirumab
Time frame: Cycle 7, Day 1: Prior to Infusion,1 hour (hr) Post Infusion
PK: Cmax and Cmin of Olaratumab
Time frame: Cycle 3, Day 1: Prior to Infusion, 1 hr Post Infusion
Pharmacodynamics (PD) Profiles
Time frame: Cycle 7, Day 1: Prior to Infusion, 1 hr Post Infusion
Percentage of Participants With Anti-Olaratumab Antibodies (ADA)
Percentage of Participants with Treatment Emergent (TE) anti-olaratumab antibodies were participants with a 4-fold increase (2 dilutions) increase over a positive baseline antibody titer or for a negative baseline titer, a participant with an increase from the baseline to a level of 1:20.
Time frame: Start of Treatment to 30-day Post Infusion Follow Up (Up to 6 Months)
Percentage of Participants With Anti-Ramucirumab Antibodies (ADA)
Percentage of Participants with Treatment Emergent (TE) anti-ramucirumab antibodies were participants with a 4-fold increase (2 dilutions) increase over a positive baseline antibody titer or for a negative baseline titer, a participant with an increase from the baseline to a level of 1:20.
Time frame: Start of Treatment to 30-day Post Infusion Follow Up (Up to 6 Months)
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