Ramucirumab or Anti-PDGFR Alpha Monoclonal Antibody IMC-3G3 in Treating Patients With Recurrent Glioblastoma Multiforme
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.
|Adult Glioblastoma Multiforme||Biological: olaratumab Biological: ramucirumab||Phase 2|
|Study Design:||Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||An Open Label, Phase 2 Study Evaluating the Safety and Efficacy of IMC-3G3 or IMC-1121B in Patients With Recurrent Glioblastoma Multiforme|
- Percentage of Participants Who Achieved Progression-Free Survival Rate at 6 Months (PFS-6) [ Time Frame: Start of treatment to PD or Death Up To 6 Months ]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).
- Number of Participants With Treatment Emergent Adverse Events as Assessed by NCI CTCAE v4.0 (National Cancer Institute-Common Terminology Criteria for Adverse Events) [ Time Frame: Start of Treatment to End of Study (Up to 13 Months) ]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.
- Percentage of Participants (Pts) With Complete Response (CR), Partial Response (PR) and Minor Response (MR) (Objective Response Rate [ORR]) [ Time Frame: Start of Treatment to PD Up To 20 Months ]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.
- Median Overall Survival (OS) [ Time Frame: Start of Treatment to Death Up To 27 Months ]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.
- 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) [ Time Frame: Start of Treatment to 30-day Post Infusion Follow Up (Up to 6 Months) ]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.
- Percentage of Participants With Anti-Ramucirumab Antibodies (ADA) [ Time Frame: Start of Treatment to 30-day Post Infusion Follow Up (Up to 6 Months) ]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.
|Study Start Date:||July 2010|
|Study Completion Date:||December 2013|
|Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
Experimental: 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.
Experimental: Group 2
Patients receive olaratumab IV over 60-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00895180
|United States, Alabama|
|UAB Comprehensive Cancer Center|
|Birmingham, Alabama, United States, 35294-3410|
|United States, California|
|Jonsson Comprehensive Cancer Center at UCLA|
|Los Angeles, California, United States, 90095|
|University of California San Francisco Medical Center|
|San Francisco, California, United States, 94143|
|United States, Florida|
|H. Lee Moffitt Cancer Center and Research Institute at University of South Florida|
|Tampa, Florida, United States, 33612-9497|
|United States, Maryland|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins|
|Baltimore, Maryland, United States, 21231-2410|
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|United States, Michigan|
|Josephine Ford Cancer Center at Henry Ford Hospital|
|Detroit, Michigan, United States, 48202|
|United States, North Carolina|
|Wake Forest University Comprehensive Cancer Center|
|Winston-Salem, North Carolina, United States, 27157-1096|
|United States, Ohio|
|Cleveland Clinic Taussig Cancer Center|
|Cleveland, Ohio, United States, 44195|
|United States, Pennsylvania|
|University of Pittsburgh School of Medicine|
|Pittsburgh, Pennsylvania, United States, 15232|
|United States, Wisconsin|
|University of Wisconsin Paul P. Carbone Comprehensive Cancer Center|
|Madison, Wisconsin, United States, 53792|
|Study Chair:||Jaishri O. Blakeley, MD||Sidney Kimmel Comprehensive Cancer Center|