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

Johns Hopkins Medicine

Status and phase: Completed; Phase 2

Conditions: Adult Glioblastoma Multiforme

Treatments: Biological: olaratumab; Biological: ramucirumab

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT00895180

IMCL-CP-19-0801

U01CA137443 (U.S. NIH Grant/Contract)

ABTC-0901 CDR0000641230

ABTC-0901

Details and patient eligibility

About

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.

Full 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.

Enrollment: 80 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and 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 design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

80 participants in 2 patient groups

Group 1

Experimental group

Description:

Patients receive ramucirumab IV over 1 hour on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Treatment:

Biological: ramucirumab

Group 2

Experimental group

Description:

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.

Treatment:

Biological: olaratumab