Clinical trial NCT00895180: Ramucirumab or Anti-PDGFR Alpha Monoclonal Antibody IMC-3G3 in Treating Patients With Recurrent Glioblastoma Multiforme
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Adult Glioblastoma Multiforme
Keywords: recurrent adult brain tumor
adult glioblastoma
adult giant cell glioblastoma
adult gliosarcoma
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: Eli Lilly and Company
First posted: 2009-05-08
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Percentage of Participants Who Achieved Progression-Free Survival Rate at 6 Months (PFS-6)
timeFrame: Start of treatment to PD or Death Up To 6 Months
Secondary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events as Assessed by NCI CTCAE v4.0 (National Cancer Institute-Common Terminology Criteria for Adverse Events)
timeFrame: Start of Treatment to End of Study (Up to 13 Months)
measure: Percentage of Participants (Pts) With Complete Response (CR), Partial Response (PR) and Minor Response (MR) (Objective Response Rate [ORR])
timeFrame: Start of Treatment to PD Up To 20 Months
measure: Median Overall Survival (OS)
timeFrame: Start of Treatment to Death Up To 27 Months
measure: Pharmacokinetics (PK): Concentration Maximum (Cmax) and Concentration Minimum (Cmin) of Ramucirumab
timeFrame: Cycle 7, Day 1: Prior to Infusion,1 hour (hr) Post Infusion
measure: PK: Cmax and Cmin of Olaratumab
timeFrame: Cycle 3, Day 1: Prior to Infusion, 1 hr Post Infusion
measure: Pharmacodynamics (PD) Profiles
timeFrame: Cycle 7, Day 1: Prior to Infusion, 1 hr Post Infusion
measure: Percentage of Participants With Anti-Olaratumab Antibodies (ADA)
timeFrame: Start of Treatment to 30-day Post Infusion Follow Up (Up to 6 Months)
measure: Percentage of Participants With Anti-Ramucirumab Antibodies (ADA)
timeFrame: Start of Treatment to 30-day Post Infusion Follow Up (Up to 6 Months)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: UAB Comprehensive Cancer Center
state: Alabama
city: Los Angeles
country: United States
facility: Jonsson Comprehensive Cancer Center at UCLA
state: California
city: San Francisco
country: United States
facility: University of California San Francisco Medical Center
state: California
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
state: Florida
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Josephine Ford Cancer Center at Henry Ford Hospital
state: Michigan
city: Winston-Salem
country: United States
facility: Wake Forest University Comprehensive Cancer Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh School of Medicine
state: Pennsylvania
city: Madison
country: United States
facility: University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
state: Wisconsin
Study officials:
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Jaishri O. Blakeley, MD
role: STUDY_CHAIR
References: