Ramucirumab or Anti-PDGFR Alpha Monoclonal Antibody IMC-3G3 in Treating Patients With Recurrent Glioblastoma Multiforme
Condition: Adult Glioblastoma Multiforme
MeSH terms: Glioblastoma
Intervention: olaratumab; ramucirumab
Intervention description: Given IV; Given IV
Intervention MeSH terms: Ramucirumab; Olaratumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 80.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: recurrent adult brain tumor; adult glioblastoma; adult giant cell glioblastoma; adult gliosarcoma

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.
    

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