Adult Glioblastoma Multiforme Clinical Trial
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
| Verified date | November 2017 |
| Source | Sidney Kimmel Comprehensive Cancer Center |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 80 |
| Est. completion date | March 4, 2014 |
| Est. primary completion date | June 22, 2012 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility |
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)a/ß, 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 |
| Country | Name | City | State |
|---|---|---|---|
| United States | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore | Maryland |
| United States | UAB Comprehensive Cancer Center | Birmingham | Alabama |
| United States | Massachusetts General Hospital | Boston | Massachusetts |
| United States | Cleveland Clinic Taussig Cancer Center | Cleveland | Ohio |
| United States | Josephine Ford Cancer Center at Henry Ford Hospital | Detroit | Michigan |
| United States | Jonsson Comprehensive Cancer Center at UCLA | Los Angeles | California |
| United States | University of Wisconsin Paul P. Carbone Comprehensive Cancer Center | Madison | Wisconsin |
| United States | University of Pittsburgh School of Medicine | Pittsburgh | Pennsylvania |
| United States | University of California San Francisco Medical Center | San Francisco | California |
| United States | H. Lee Moffitt Cancer Center and Research Institute at University of South Florida | Tampa | Florida |
| United States | Wake Forest University Comprehensive Cancer Center | Winston-Salem | North Carolina |
| Lead Sponsor | Collaborator |
|---|---|
| Sidney Kimmel Comprehensive Cancer Center | ImClone LLC, National Cancer Institute (NCI) |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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 | Number of Participants With Treatment Emergent Adverse Events as Assessed by NCI CTCAE v4.0 (National Cancer Institute-Common Terminology Criteria for Adverse Events) | The number of participants who experienced serious adverse events (SAEs) that were considered to be related to ramucirumab or olaratumab. A summary of other non-serious adverse events and all serious adverse events, regardless of causality, is located in the Reported Adverse Events Section. | Start of Treatment to End of Study (Up to 13 Months) | |
| Secondary | Percentage of Participants (Pts) With Complete Response (CR), Partial Response (PR) and Minor Response (MR) (Objective Response Rate [ORR]) | The pts achievement of both measurement and confirmation criteria for a status of CR, PR or MR based on the modified RANO criteria.CR requires all of the following:complete disappearance of all enhancing measurable and non-measurable disease sustained for at least 4 weeks (wks);no new lesions;no corticosteroids;and stable or improved clinically.PR requires all of the following:= 50% decrease compared with baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions sustained for at least 4 wks;no new lesions;stable or reduced corticosteroid dose;and stable or improved clinically.MR requires = 25% reduction in sum of products of the perpendicular diameters of all measureable enhancing lesions sustained for at least 4 wks and no new lesions or progression of non-measurable lesions. PD is defined by any of these: = 25% increase in sum of the products of perpendicular diameters of enhancing lesions;any new lesion;or clinical deterioration. | Start of Treatment to PD Up To 20 Months | |
| Secondary | Median Overall Survival (OS) | OS is the time from the start of treatment to the date of death. Participants who had not expired by the data analysis cutoff date were censored at their last date known to be alive. | Start of Treatment to Death Up To 27 Months | |
| Secondary | Pharmacokinetics (PK): Concentration Maximum (Cmax) and Concentration Minimum (Cmin) of Ramucirumab | Cycle 7, Day 1: Prior to Infusion,1 hour (hr) Post Infusion | ||
| Secondary | PK: Cmax and Cmin of Olaratumab | Cycle 3, Day 1: Prior to Infusion, 1 hr Post Infusion | ||
| Secondary | Pharmacodynamics (PD) Profiles | Cycle 7, Day 1: Prior to Infusion, 1 hr Post Infusion | ||
| Secondary | Percentage of Participants With Anti-Olaratumab Antibodies (ADA) | Percentage of Participants with Treatment Emergent (TE) anti-olaratumab antibodies were participants with a 4-fold increase (2 dilutions) increase over a positive baseline antibody titer or for a negative baseline titer, a participant with an increase from the baseline to a level of 1:20. | Start of Treatment to 30-day Post Infusion Follow Up (Up to 6 Months) | |
| Secondary | Percentage of Participants With Anti-Ramucirumab Antibodies (ADA) | Percentage of Participants with Treatment Emergent (TE) anti-ramucirumab antibodies were participants with a 4-fold increase (2 dilutions) increase over a positive baseline antibody titer or for a negative baseline titer, a participant with an increase from the baseline to a level of 1:20. | Start of Treatment to 30-day Post Infusion Follow Up (Up to 6 Months) |