Glioblastoma
Conditions
Keywords
recurrent glioblastoma multiforme (GBM), CVX-060, PF-04856884, phase 2, open-label, bevacizumab, anti-angiogenic
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Notification of study being cancelled resulted in update in overall status change from not yet recruiting to withdrawn.
Interventions
BIOLOGICALPF-04856884
PF-04856884 at a dose of 15 mg/kg/week
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression free survival rate at Month 6 (PFS6) defined as the patient progression free status at Month 6. | 1 year |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| Corticosteroid doses at baseline and on-study | 4 months |
| 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 |
| Overall survival (OS) defined as the time from first dose of study drug to death due to any cause. | 2 years |
Outcome results
None listed