Phase 2
N=80
Ramucirumab or Anti-PDGFR Alpha Monoclonal Antibody IMC-3G3 in Treating Patients With Recurrent Glioblastoma Multiforme
Adult Glioblastoma Multiforme
Bottom Line
View on ClinicalTrials.gov: NCT00895180 ↗Enrolled (actual)
80
Serious AEs
33.8%
Results posted
Mar 2017
Primary outcome: Primary: Percentage of Participants Who Achieved Progression-Free Survival Rate at 6 Months (PFS-6) — 12.5; 7.5 percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- olaratumab (Biological); ramucirumab (Biological)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
- Primary completion
- Jun 2012
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants Who Achieved Progression-Free Survival Rate at 6 Months (PFS-6) |
12.5; 7.5 | — |
| 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) |
13; 14; 38; 39 | — |
| SECONDARY Percentage of Participants (Pts) With Complete Response (CR), Partial Response (PR) and Minor Response (MR) (Objective Response Rate [ORR]) |
0; 2.5 | — |
| SECONDARY Median Overall Survival (OS) |
49.5; 34.3 | — |
| SECONDARY Pharmacokinetics (PK): Concentration Maximum (Cmax) and Concentration Minimum (Cmin) of Ramucirumab |
85.0; 396 | — |
| SECONDARY PK: Cmax and Cmin of Olaratumab |
145; 515 | — |
| SECONDARY Pharmacodynamics (PD) Profiles |
— | — |
| SECONDARY Percentage of Participants With Anti-Olaratumab Antibodies (ADA) |
— | — |
| SECONDARY Percentage of Participants With Anti-Ramucirumab Antibodies (ADA) |
3.1 | — |
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
Data sourced from ClinicalTrials.gov (NCT00895180). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.