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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
ImClone LLC
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00895180
First received: May 7, 2009
Last updated: September 20, 2013
Last verified: September 2013
  Purpose

RATIONALE: Monoclonal antibodies, such as ramucirumab and anti-PDGFR alpha monoclonal antibody IMC-3G3, 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.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Biological: anti-PDGFR alpha monoclonal antibody IMC-3G3
Biological: ramucirumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures:
  • Progression-free survival rate at 6 months [ Time Frame: continous ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Acute and late toxicities as assessed by NCI CTCAE v4.0 [ Time Frame: continous ] [ Designated as safety issue: Yes ]
  • Objective tumor response rate [ Time Frame: continous ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: continous ] [ Designated as safety issue: No ]
  • Pharmacokinetic and pharmacodynamic profiles and immunogenicity [ Time Frame: continous ] [ Designated as safety issue: No ]

Estimated Enrollment: 80
Study Start Date: July 2010
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Biological: ramucirumab
Given IV
Experimental: 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.
Biological: anti-PDGFR alpha monoclonal antibody IMC-3G3
Given IV

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.

Patients undergo blood sample collection periodically for pharmacokinetic, pharmacodynamic biomarker (i.e., PDGFRα, PDGF, VEGF, VEGFR-1, and VEGFR-2), and immunogenicity analyses.

After completion of study treatment, patients are followed every 2 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin ≥ 9 g/dL
  • Creatinine ≤ 1.5 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
  • INR ≤ 1.5
  • 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 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 PDGFRα/β, PDGF, VEGF, or VEGFRs
  • 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, G-CSF, GM-CSF, or 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00895180

Locations
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
UCSF Medical Center at Parnassus
San Francisco, California, United States, 94143
United States, Georgia
Emory University Hospital - Atlanta
Atlanta, Georgia, United States, 30322
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, 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
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
ImClone LLC
Investigators
Study Chair: Jaishri O. Blakeley, MD Sidney Kimmel Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00895180     History of Changes
Other Study ID Numbers: ABTC-0901 CDR0000641230, U01CA137443, ABTC-0901, IMCL-CP-19-0801
Study First Received: May 7, 2009
Last Updated: September 20, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
recurrent adult brain tumor
adult glioblastoma
adult giant cell glioblastoma
adult gliosarcoma

Additional relevant MeSH terms:
Glioblastoma
Nervous System Neoplasms
Central Nervous System Neoplasms
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms by Site
Nervous System Diseases
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 26, 2014