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

Primary Purpose

Adult Glioblastoma Multiforme

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
olaratumab
ramucirumab
Sponsored by
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adult Glioblastoma Multiforme focused on measuring recurrent adult brain tumor, adult glioblastoma, adult giant cell glioblastoma, adult gliosarcoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • UAB Comprehensive Cancer Center
  • Jonsson Comprehensive Cancer Center at UCLA
  • University of California San Francisco Medical Center
  • H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
  • Massachusetts General Hospital
  • Josephine Ford Cancer Center at Henry Ford Hospital
  • Wake Forest University Comprehensive Cancer Center
  • Cleveland Clinic Taussig Cancer Center
  • University of Pittsburgh School of Medicine
  • University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Group 1

Group 2

Arm 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.

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.

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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.
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.
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.
Pharmacokinetics (PK): Concentration Maximum (Cmax) and Concentration Minimum (Cmin) of Ramucirumab
PK: Cmax and Cmin of Olaratumab
Pharmacodynamics (PD) Profiles
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.
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.

Full Information

First Posted
May 7, 2009
Last Updated
November 30, 2017
Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
National Cancer Institute (NCI), Eli Lilly and Company
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1. Study Identification

Unique Protocol Identification Number
NCT00895180
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
Study Type
Interventional

2. Study Status

Record Verification Date
November 2017
Overall Recruitment Status
Completed
Study Start Date
July 2010 (undefined)
Primary Completion Date
June 22, 2012 (Actual)
Study Completion Date
March 4, 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
National Cancer Institute (NCI), Eli Lilly and Company

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adult Glioblastoma Multiforme
Keywords
recurrent adult brain tumor, adult glioblastoma, adult giant cell glioblastoma, adult gliosarcoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
80 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group 1
Arm Type
Experimental
Arm 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.
Arm Title
Group 2
Arm Type
Experimental
Arm 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.
Intervention Type
Biological
Intervention Name(s)
olaratumab
Other Intervention Name(s)
anti-PDGFR alpha monoclonal antibody, IMC-3G3
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
ramucirumab
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Percentage of Participants Who Achieved Progression-Free Survival Rate at 6 Months (PFS-6)
Description
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).
Time Frame
Start of treatment to PD or Death Up To 6 Months
Secondary Outcome Measure Information:
Title
Number of Participants With Treatment Emergent Adverse Events as Assessed by NCI CTCAE v4.0 (National Cancer Institute-Common Terminology Criteria for Adverse Events)
Description
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.
Time Frame
Start of Treatment to End of Study (Up to 13 Months)
Title
Percentage of Participants (Pts) With Complete Response (CR), Partial Response (PR) and Minor Response (MR) (Objective Response Rate [ORR])
Description
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.
Time Frame
Start of Treatment to PD Up To 20 Months
Title
Median Overall Survival (OS)
Description
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.
Time Frame
Start of Treatment to Death Up To 27 Months
Title
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
Title
PK: Cmax and Cmin of Olaratumab
Time Frame
Cycle 3, Day 1: Prior to Infusion, 1 hr Post Infusion
Title
Pharmacodynamics (PD) Profiles
Time Frame
Cycle 7, Day 1: Prior to Infusion, 1 hr Post Infusion
Title
Percentage of Participants With Anti-Olaratumab Antibodies (ADA)
Description
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.
Time Frame
Start of Treatment to 30-day Post Infusion Follow Up (Up to 6 Months)
Title
Percentage of Participants With Anti-Ramucirumab Antibodies (ADA)
Description
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.
Time Frame
Start of Treatment to 30-day Post Infusion Follow Up (Up to 6 Months)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jaishri O. Blakeley, MD
Organizational Affiliation
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Official's Role
Study Chair
Facility Information:
Facility Name
UAB Comprehensive Cancer Center
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294-3410
Country
United States
Facility Name
Jonsson Comprehensive Cancer Center at UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
University of California San Francisco Medical Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612-9497
Country
United States
Facility Name
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231-2410
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Josephine Ford Cancer Center at Henry Ford Hospital
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Wake Forest University Comprehensive Cancer Center
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157-1096
Country
United States
Facility Name
Cleveland Clinic Taussig Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
University of Pittsburgh School of Medicine
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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