Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Biomarker/Laboratory analysis, Treatment	Approved-not yet active	18 and over	NCI	ABTC-0901 ABTC 0901, NCT00895180

Objectives

Primary

1. 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

1. To evaluate the acute and late toxicities associated with these regimens.
2. To assess the objective tumor response rate.
3. To estimate the overall survival of these patients.
4. To describe the pharmacokinetic and pharmacodynamic profiles and immunogenicity of these regimens.

Entry 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

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

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 ≥ 8 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

Expected Enrollment

Outcomes

Progression-free survival rate at 6 months

Acute and late toxicities as assessed by NCI CTCAE v3.0
Objective tumor response rate
Overall survival
Pharmacokinetic and pharmacodynamic profiles and immunogenicity

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.

Trial Contact Information

Trial Lead Organizations

Adult Brain Tumor Consortium

Jaishri Blakeley, MD, Protocol chair		Ph: 410-955-8837

Registry Information
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
Trial Start Date		2009-03-01 (estimated)
Trial Completion Date		2010-04-01 (estimated)
Registered in ClinicalTrials.gov		NCT00895180
Date Submitted to PDQ		2009-04-29
Information Last Verified		2009-05-06
NCI Grant/Contract Number		CA137433