A Trial Of PF-04856884 In Patients With Recurrent Glioblastoma

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.