Adult Glioblastoma MultiformePhase 2NCT00895180
Ramucirumab or Anti-PDGFR Alpha Monoclonal Antibody IMC-3G3 in Treating Patients With Recurrent Glioblastoma Multiforme
A Phase 2 study testing olaratumab and ramucirumab in people with Adult Glioblastoma Multiforme, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 11 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adult Glioblastoma Multiforme
- What is being tested?
- olaratumab and ramucirumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 11 sitesUnited States
- Study dates
- Jul 2010to 4 Mar 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United States11 sites
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, 21231-2410
UAB Comprehensive Cancer Center
Birmingham, Alabama, 35294-3410
Massachusetts General Hospital
Boston, Massachusetts, 02114
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, 44195
Josephine Ford Cancer Center at Henry Ford Hospital
Detroit, Michigan, 48202
Jonsson Comprehensive Cancer Center at UCLA
Los Angeles, California, 90095
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
Madison, Wisconsin, 53792
University of Pittsburgh School of Medicine
Pittsburgh, Pennsylvania, 15232
University of California San Francisco Medical Center
San Francisco, California, 94143
H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
Tampa, Florida, 33612-9497
Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, 27157-1096
About this study
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
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.
Read the 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.
- Conditions
- Adult Glioblastoma Multiforme
- Being tested
- olaratumab, ramucirumab
- Keywords
- recurrent adult brain tumor, adult glioblastoma, adult giant cell glioblastoma, adult gliosarcoma
- Medical subject headings
- Glioblastoma, Brain Neoplasms, Gliosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
olaratumabBiological
Also called anti-PDGFR alpha monoclonal antibody, IMC-3G3
Given IV
ramucirumabBiological
Given IV
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Biological: olaratumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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)
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.
Measured: 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])
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.
Measured: Start of Treatment to PD Up To 20 Months
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.
Measured: Start of Treatment to Death Up To 27 Months
Pharmacokinetics (PK): Concentration Maximum (Cmax) and Concentration Minimum (Cmin) of Ramucirumab
Measured: Cycle 7, Day 1: Prior to Infusion,1 hour (hr) Post Infusion
PK: Cmax and Cmin of Olaratumab
Measured: Cycle 3, Day 1: Prior to Infusion, 1 hr Post Infusion
Pharmacodynamics (PD) Profiles
Measured: Cycle 7, Day 1: Prior to Infusion, 1 hr Post Infusion
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.
Measured: Start of Treatment to 30-day Post Infusion Follow Up (Up to 6 Months)
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.
Measured: Start of Treatment to 30-day Post Infusion Follow Up (Up to 6 Months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2009 (estimated)
- Study startJul 2010
- Primary completion22 Jun 2012
- Study completion4 Mar 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Adult Glioblastoma MultiformeStudies of the same condition, open and under way.
- More trials run by Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), Eli Lilly and Company
- Responsible party
- Sponsor
- Investigators
- Jaishri O. Blakeley, MD, Study chair, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00895180
- Sponsor's protocol ID
- ABTC-0901 CDR0000641230
- Other IDs
- U01CA137443, ABTC-0901, IMCL-CP-19-0801
- Status last verified
- Nov 2017
- First submitted
- 7 May 2009
- Last updated
- 27 Dec 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 27 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00895180
- Acronym / sponsor ID
- ABTC-0901 CDR0000641230
- Conditions
- Adult Glioblastoma Multiforme
- Keywords
- recurrent adult brain tumor, adult glioblastoma, adult giant cell glioblastoma, adult gliosarcoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), Eli Lilly and Company
- Study start
- Jul 2010
- Primary completion
- 22 Jun 2012 (actual)
- Study completion
- 4 Mar 2014 (actual)
- First posted
- 8 May 2009 (estimated)
- Results
- Posted 29 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Experimental | Biological: ramucirumabPatients 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 | Experimental | Biological: olaratumabPatients receive olaratumab IV over 60-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| olaratumabAlso: anti-PDGFR alpha monoclonal antibody, IMC-3G3Given IV | Biological | Group 2 |
| ramucirumabGiven IV | Biological | Group 1 |
Primary outcome
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).
8 secondary outcomes
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)
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
Median Overall Survival (OS)
Time frame: Start of Treatment to Death Up To 27 Months
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 Anti-Ramucirumab Antibodies (ADA)
Time frame: Start of Treatment to 30-day Post Infusion Follow Up (Up to 6 Months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Dec 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jaishri O. Blakeley, MD study chair
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing olaratumab and ramucirumab in people with Adult Glioblastoma Multiforme, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 11 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Mar 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Dec 2017.