A Trial Of PF-04856884 In Patients With Recurrent Glioblastoma
Study Details
Study Description
Brief Summary
Angiopoietin-2 (Ang-2) is a protein in the body which destabilizes blood vessels and is important in stimulating tumor blood vessels. There is evidence suggesting that Ang-2 may be important for the growth and progression of Glioblastoma multiforme (GBM). PF- 04856884 (CVX-060) is a compound which binds Ang-2 and prevents its activity. The hypothesis is that PF-04856884 will be safe and effective in patients with recurrent Glioblastoma multiforme (GBM).
Condition or Disease | Intervention/Treatment | Phase |
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Phase 2 |
Detailed Description
Notification of study being cancelled resulted in update in overall status change from "not yet recruiting" to "withdrawn."
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Primary Cohort
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Biological: PF-04856884
PF-04856884 at a dose of 15 mg/kg/week
Other Names:
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Experimental: Exploratory Cohort
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Biological: PF-04856884
PF-04856884 at a dose of 15 mg/kg/week
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Progression free survival rate at Month 6 (PFS6) defined as the patient progression free status at Month 6. [1 year]
Secondary Outcome Measures
- Corticosteroid doses at baseline and on-study [4 months]
- Overall Response Rate (ORR) [2 years]
- PFS defined as the time from 1st dose of study drug to the 1st documentation of disease progression or death from any cause, whichever comes first. [2 years]
- Time to death is defined as the time from first study drug to death due to any cause. [2 years]
- Overall survival (OS) defined as the time from first dose of study drug to death due to any cause. [2 years]
- OS6 defined as the patient survival status at Month 6. The OS6 rate will be obtained as a Kaplan-Meier estimate of the time to death at Month 6. [2 years]
- Immunogenicity determined by measuring anti-PF-04856884 antibodies following therapy [4 months]
- Dynamic Contrast Enhanced Magnetic Resonance Imaging [DCE-MRI] endpoints to include changes from baseline volume transfer coefficient [Ktrans] and/or the initial area under the contrast agent concentration-time curve [IAUC] or Ki following therapy [4 months]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Tumor eligibility: Primary Cohort: Measurable disease; Exploratory Cohort: Measurable disease as defined above or non-measurable/evaluable disease (eg, progressing non-enhancing lesions).
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Histologically or cytologically confirmed recurrent GBM in 1st or 2nd relapse: Primary Cohort: Recurrence following radiation therapy and temozolomide, less than or equal to 2 prior chemotherapeutic regimens; Exploratory cohort: Prior radiation therapy, temozolomide, and bevacizumab, Recurrence of disease within 2-4 weeks of last bevacizumab dose.
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Stable dose of corticosteroids for greater than or equal to 5 days prior to baseline Magnetic Resonance Imaging (MRI)
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Adequate organ function
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Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
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Life expectancy greater than or equal to 12 weeks.
Exclusion Criteria:
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Patients who have previously received a trial drug containing the core platform antibody (eg, CVX-045, PF-04856884 (CVX-060), CVX-096, PF-05057459 (CVX-241), etc.).
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History of pathologic fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months of therapy.
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Evidence of bleeding diathesis or coagulopathy.
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Major surgical procedure (eg, craniotomy), open biopsy, significant traumatic injury within 28 days prior to therapy or anticipation of need for a major surgical procedure during the course of the trial.
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Minor surgical procedures, fine needle aspiration or core biopsies within 7 days prior to therapy.
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Serious non-healing wound, ulcer, or bone fracture.
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Active gastrointestinal bleeding, as evidenced by either hematemesis, hematochezia, or melena in prior 6 months.
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Hemoptysis >½ teaspoon per day within 1 week of enrollment.
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National Cancer Institute-Common Terminology Criteria for Adverse Events [NCI CTCAE] Grade 3 hemorrhage from any cause <4 weeks prior to enrollment.
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Participation in any investigational drug study within 28 days prior to study therapy.
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Evidence of preexisting uncontrolled hypertension
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Clinically significant cardiovascular disease within the 12 months prior to starting trial treatment
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Prolongation of the QT interval corrected [QTc] interval to >450 msec for men or >470 msec for women.
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History of allergic or anaphylactic reaction to any therapeutic or diagnostic monoclonal antibody or IgG-fusion protein.
Exclusion Criteria Specific for Primary Cohort
- Prior therapy with bevacizumab or other anti-Vascular Endothelial Growth Factor [VEGF] agents for the treatment of GBM.
Exclusion Criteria Specific for Exploratory Cohort
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Patients discontinued from prior bevacizumab or anti-VEGF agents due to toxicity.
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Patients who have failed 2 prior anti-VEGF therapies.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Pfizer
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- B1131003