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

• ClinicalTrials.gov Identifier: NCT00895180
• Recruitment Status: Completed
• First Posted: May 8, 2009
• Results First Posted: March 29, 2017
• Last Update Posted: December 27, 2017
• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: National Cancer Institute (NCI); Eli Lilly and Company
• Information provided by (Responsible Party): Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Tracking Information

• First Submitted Date: May 7, 2009
• First Posted Date: May 8, 2009
• Results First Submitted Date: November 18, 2016
• Results First Posted Date: March 29, 2017
• Last Update Posted Date: December 27, 2017
• Study Start Date: July 2010
• Actual Primary Completion Date: June 22, 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 13, 2017)

Percentage of Participants Who Achieved Progression-Free Survival Rate at 6 Months (PFS-6) [ Time Frame: Start of treatment to PD or Death Up To 6 Months ]

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).

• Original Primary Outcome Measures (submitted: May 7, 2009): Progression-free survival rate at 6 months

Current Secondary Outcome Measures (submitted: February 13, 2017)

• Number of Participants With Treatment Emergent Adverse Events as Assessed by NCI CTCAE v4.0 (National Cancer Institute-Common Terminology Criteria for Adverse Events) [ Time Frame: Start of Treatment to End of Study (Up to 13 Months) ]
  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.
• Percentage of Participants (Pts) With Complete Response (CR), Partial Response (PR) and Minor Response (MR) (Objective Response Rate [ORR]) [ Time Frame: Start of Treatment to PD Up To 20 Months ]
  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.
• Median Overall Survival (OS) [ Time Frame: Start of Treatment to Death Up To 27 Months ]
  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.
• Pharmacokinetics (PK): Concentration Maximum (Cmax) and Concentration Minimum (Cmin) of Ramucirumab [ Time Frame: Cycle 7, Day 1: Prior to Infusion,1 hour (hr) Post Infusion ]
• PK: Cmax and Cmin of Olaratumab [ Time Frame: Cycle 3, Day 1: Prior to Infusion, 1 hr Post Infusion ]
• Pharmacodynamics (PD) Profiles [ Time Frame: Cycle 7, Day 1: Prior to Infusion, 1 hr Post Infusion ]
• Percentage of Participants With Anti-Olaratumab Antibodies (ADA) [ Time Frame: Start of Treatment to 30-day Post Infusion Follow Up (Up to 6 Months) ]
  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.
• Percentage of Participants With Anti-Ramucirumab Antibodies (ADA) [ Time Frame: Start of Treatment to 30-day Post Infusion Follow Up (Up to 6 Months) ]
  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.

Original Secondary Outcome Measures (submitted: May 7, 2009)

• Acute and late toxicities as assessed by NCI CTCAE v3.0
• Objective tumor response rate
• Overall survival
• Pharmacokinetic and pharmacodynamic profiles and immunogenicity

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

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.

Detailed 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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Adult Glioblastoma Multiforme

Intervention

• Biological: olaratumab
  Given IV
  Other Names:

  • anti-PDGFR alpha monoclonal antibody
  • IMC-3G3
• Biological: ramucirumab
  Given IV

Study Arms

• Experimental: 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.
  Intervention: Biological: ramucirumab
• Experimental: Group 2
  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.
  Intervention: Biological: olaratumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 7, 2009): 80
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: March 4, 2014
• Actual Primary Completion Date: June 22, 2012 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00895180
• Other Study ID Numbers: ABTC-0901 CDR0000641230; U01CA137443 ( U.S. NIH Grant/Contract ); ABTC-0901; IMCL-CP-19-0801
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Original Responsible Party: Not Provided
• Current Study Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Original Study Sponsor: National Cancer Institute (NCI)

Collaborators

• National Cancer Institute (NCI)
• Eli Lilly and Company

Investigators

• Study Chair: Jaishri O. Blakeley, MD; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

• PRS Account: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Verification Date: November 2017