A Trial Of PF-04856884 In Patients With Recurrent Glioblastoma
Phase 2
Withdrawn
- Conditions
- Glioblastoma
- Registration Number
- NCT01225510
- Lead Sponsor
- Pfizer
- 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).
- Detailed Description
Notification of study being cancelled resulted in update in overall status change from "not yet recruiting" to "withdrawn."
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
Inclusion Criteria
- Tumor eligibility: Primary Cohort: Measurable disease; Exploratory Cohort: Measurable disease as defined above or non-measurable/evaluable disease (eg, progressing non-enhancing lesions).
- 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.
- Stable dose of corticosteroids for greater than or equal to 5 days prior to baseline Magnetic Resonance Imaging (MRI)
- Adequate organ function
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Life expectancy greater than or equal to 12 weeks.
Exclusion Criteria
- 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.).
- History of pathologic fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months of therapy.
- Evidence of bleeding diathesis or coagulopathy.
- 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.
- Minor surgical procedures, fine needle aspiration or core biopsies within 7 days prior to therapy.
- Serious non-healing wound, ulcer, or bone fracture.
- Active gastrointestinal bleeding, as evidenced by either hematemesis, hematochezia, or melena in prior 6 months.
- Hemoptysis >½ teaspoon per day within 1 week of enrollment.
- National Cancer Institute-Common Terminology Criteria for Adverse Events [NCI CTCAE] Grade 3 hemorrhage from any cause <4 weeks prior to enrollment.
- Participation in any investigational drug study within 28 days prior to study therapy.
- Evidence of preexisting uncontrolled hypertension
- Clinically significant cardiovascular disease within the 12 months prior to starting trial treatment
- Prolongation of the QT interval corrected [QTc] interval to >450 msec for men or >470 msec for women.
- 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
- Patients discontinued from prior bevacizumab or anti-VEGF agents due to toxicity.
- Patients who have failed 2 prior anti-VEGF therapies.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Primary Outcome Measures
Name Time Method Progression free survival rate at Month 6 (PFS6) defined as the patient progression free status at Month 6. 1 year
- Secondary Outcome Measures
Name Time Method 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 Corticosteroid doses at baseline and on-study 4 months