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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

DISEASE CHARACTERISTICS:

  • - Histologically confirmed supratentorial glioblastoma multiforme (GBM) - Patients with prior low-grade glioma who progressed after radiotherapy ± chemotherapy and are biopsied and found to have GBM are eligible.
  • - 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

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT00895180
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Jaishri O. Blakeley, MD
Principal Investigator Affiliation Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other, NIH, Industry
Overall Status Completed
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Adult Glioblastoma Multiforme
Additional Details

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.

Arms & Interventions

Arms

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.

Interventions

Biological: - olaratumab

Given IV

Biological: - ramucirumab

Given IV

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

UAB Comprehensive Cancer Center, Birmingham, Alabama

Status

Address

UAB Comprehensive Cancer Center

Birmingham, Alabama, 35294-3410

Los Angeles, California

Status

Address

Jonsson Comprehensive Cancer Center at UCLA

Los Angeles, California, 90095

San Francisco, California

Status

Address

University of California San Francisco Medical Center

San Francisco, California, 94143

Tampa, Florida

Status

Address

H. Lee Moffitt Cancer Center and Research Institute at University of South Florida

Tampa, Florida, 33612-9497

Baltimore, Maryland

Status

Address

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231-2410

Massachusetts General Hospital, Boston, Massachusetts

Status

Address

Massachusetts General Hospital

Boston, Massachusetts, 02114

Detroit, Michigan

Status

Address

Josephine Ford Cancer Center at Henry Ford Hospital

Detroit, Michigan, 48202

Winston-Salem, North Carolina

Status

Address

Wake Forest University Comprehensive Cancer Center

Winston-Salem, North Carolina, 27157-1096

Cleveland Clinic Taussig Cancer Center, Cleveland, Ohio

Status

Address

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, 44195

Pittsburgh, Pennsylvania

Status

Address

University of Pittsburgh School of Medicine

Pittsburgh, Pennsylvania, 15232

Madison, Wisconsin

Status

Address

University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

Madison, Wisconsin, 53792