Ramucirumab or Anti-PDGFR Alpha Monoclonal Antibody IMC-3G3 in Treating Patients With Recurrent Glioblastoma Multiforme

NCT ID: NCT00895180

Last Updated: 2017-12-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-07-31
• Study Completion Date: 2014-03-04

Brief Summary

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.

Detailed Description

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.

Conditions

Adult Glioblastoma Multiforme

Keywords

recurrent adult brain tumor; adult glioblastoma; adult giant cell glioblastoma; adult gliosarcoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study 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 Type: EXPERIMENTAL

ramucirumab

Intervention Type: BIOLOGICAL

Given IV

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.

Group Type: EXPERIMENTAL

olaratumab

Intervention Type: BIOLOGICAL

Given IV

Interventions

olaratumab

Given IV

Intervention Type: BIOLOGICAL

ramucirumab

Given IV

Intervention Type: BIOLOGICAL

Other Intervention Names

anti-PDGFR alpha monoclonal antibody; IMC-3G3

Eligibility Criteria

Inclusion Criteria

• Progressive or recurrent disease after radiotherapy ± chemotherapy
• Measurable disease by contrast-enhanced MRI or CT scan

PATIENT CHARACTERISTICS:

• Karnofsky performance status 60-100%
• Life expectancy ≥ 3 months
• Absolute neutrophil count ≥ 1,500/millimeter cubed (mm³)
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 9 gram/deciliter (g/dL)
• Creatinine ≤ 1.5 milligram/deciliter (mg/dL) OR creatinine clearance > 60 mL/min
• Total bilirubin ≤ 1.5 mg/dL
• Transaminases ≤ 3 times upper limit of normal (ULN)
• Urine protein ≤ 2+ by dipstick or urinalysis or ≤ 1,000 mg by 24-hour urine collection
• International Normalized Ratio (INR) ≤ 1.5
• Partial Thromboplastin Time (PTT) ≤ 5 seconds above ULN
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for ≥ 12 weeks after completion of study treatment
• Mini Mental State Exam score ≥ 15
• Able to undergo magnetic resonance imaging (MRI) (i.e., no pacemaker, aneurysm clip, or claustrophobia)
• No concurrent serious infection or medical illness that would jeopardize the ability of the patient to receive the treatment outlined in this study with reasonable safety including, but not limited to, any of the following:

• Uncontrolled hypertension
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Cardiac arrhythmia
• Psychiatric illness/social situation that would limit compliance with study requirements
• No other malignancy within the past 5 years, except curatively treated carcinoma in situ or basal cell carcinoma of the skin
• No major bleeding episode within the past 3 months
• No myocardial infarction, unstable angina pectoris, cerebrovascular accident, or transient ischemic attack within the past 6 months
• No serious or non-healing wound, ulcer, or bone fracture
• No uncontrolled or poorly controlled hypertension, despite standard medical management
• No known allergy to any of the treatment components
• No known HIV positivity or AIDS-related illness
• No uncontrolled thrombotic or hemorrhagic disorders
• No grade 3-4 gastrointestinal bleeding within the past 3 months
• No gross hemoptysis (≥ ½ teaspoon) within the past 2 months

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered from prior therapy
• At least 3 months since prior radiotherapy
• At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas)
• At least 2 weeks since prior FDA-approved, non-cytotoxic agents (e.g., celecoxib, thalidomide)
• At least 3 weeks since prior investigational, non-cytotoxic agents
• More than 28 days since prior major surgery, including brain biopsy
• More than 7 days since prior subcutaneous venous access device placement
• No prior treatment with other agents that directly inhibit Platelet-Derived Growth Factor Receptor (PDGFR)α/β, Platelet-Derived Growth Factor (PDGF), Vascular Endothelial Growth Factor (VEGF), or Vascular Endothelial Growth Factor Receptor (VEGFR)s
• No concurrent therapeutic anticoagulation, chronic daily treatment with aspirin (> 325 mg/day), or other known inhibitors of platelet function
• No concurrent prophylactic hematopoietic growth factors (e.g., erythropoietin, Granulocyte Colony Stimulating Factor (G-CSF), Granulocyte-macrophage Colony Stimulating Factor (GM-CSF), or Interleukin (IL-11) during the first course of treatment
• No concurrent elective or planned surgery
• No other concurrent therapy for the tumor (e.g., chemotherapy or investigational agents)

• Concurrent steroids allowed

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Eli Lilly and Company

INDUSTRY

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jaishri O. Blakeley, MD

Role: STUDY_CHAIR

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Locations

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

University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

Madison, Wisconsin, United States

Countries

United States

Other Identifiers

U01CA137443

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ABTC-0901

Identifier Type: -

Identifier Source: secondary_id

IMCL-CP-19-0801

Identifier Type: -

Identifier Source: secondary_id

ABTC-0901 CDR0000641230

Identifier Type: -

Identifier Source: org_study_id