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

NCT00895180 | Completed Phase 2 Results DMC

• 4 other identifiers: ABTC-0901 CDR0000641230U01CA137443ABTC-0901IMCL-CP-19-0801
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 11

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.

Conditions

Adult Glioblastoma Multiforme

Keywords

recurrent adult brain tumor; adult glioblastoma; adult giant cell glioblastoma; adult gliosarcoma

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Who Achieved Progression-Free Survival Rate at 6 Months (PFS-6)

  PFS was defined as the start of treatment to the earliest date of tumor progression or death from any cause based on the modified Response Assessment in Neuro-Oncology Group through the American Society of Clinical Oncology (RANO) criteria. Progression is defined by any of the following: ≥ 25% increase in sum of the products of perpendicular diameters of enhancing lesions; any new lesion; or clinical deterioration. RANO is a standardized response criteria using bi-dimensional measurements of the largest contrast-enhancing area (Macdonald, 1990).

  Start of treatment to PD or Death Up To 6 Months

Secondary Outcomes (8)

• Number of Participants With Treatment Emergent Adverse Events as Assessed by NCI CTCAE v4.0 (National Cancer Institute-Common Terminology Criteria for Adverse Events)

  Start of Treatment to End of Study (Up to 13 Months)

• Percentage of Participants (Pts) With Complete Response (CR), Partial Response (PR) and Minor Response (MR) (Objective Response Rate [ORR])

  Start of Treatment to PD Up To 20 Months

• Median Overall Survival (OS)

  Start of Treatment to Death Up To 27 Months

• Pharmacokinetics (PK): Concentration Maximum (Cmax) and Concentration Minimum (Cmin) of Ramucirumab

  Cycle 7, Day 1: Prior to Infusion,1 hour (hr) Post Infusion

• PK: Cmax and Cmin of Olaratumab

  Cycle 3, Day 1: Prior to Infusion, 1 hr Post Infusion

Study Arms (2)

Group 1

EXPERIMENTAL

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

Group 2

EXPERIMENTAL

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.

Biological: olaratumab

Interventions

olaratumab BIOLOGICAL

Given IV

Also known as: anti-PDGFR alpha monoclonal antibody, IMC-3G3

Group 2

ramucirumab BIOLOGICAL

Given IV

Group 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• National Cancer Institute (NCI): collaborator
• Eli Lilly and Company: collaborator

Study Sites (11)

UAB Comprehensive Cancer Center

Birmingham, Alabama, 35294-3410, United States

Location

Jonsson Comprehensive Cancer Center at UCLA

Los Angeles, California, 90095, United States

Location

University of California San Francisco Medical Center

San Francisco, California, 94143, United States

Location

H. Lee Moffitt Cancer Center and Research Institute at University of South Florida

Tampa, Florida, 33612-9497, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231-2410, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Josephine Ford Cancer Center at Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Wake Forest University Comprehensive Cancer Center

Winston-Salem, North Carolina, 27157-1096, United States

Location

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, 44195, United States

Location

University of Pittsburgh School of Medicine

Pittsburgh, Pennsylvania, 15232, United States

Location

University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Glioblastoma; Brain Neoplasms; Gliosarcoma

Interventions

olaratumab; Ramucirumab

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Jaishri Blakely
• Organization: Sidney Kimmel Comprehensive Cancer Center

(410) 955-8893

Study Officials

• Jaishri O. Blakeley, MD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2009
• First Posted: May 8, 2009
• Study Start: July 1, 2010
• Primary Completion: June 22, 2012
• Study Completion: March 4, 2014
• Last Updated: December 27, 2017
• Results First Posted: March 29, 2017

Record last verified: 2017-11

Locations

US (11)