Clinical trial NCT01225510: A Trial Of PF-04856884 In Patients With Recurrent Glioblastoma
Official title: A Phase 2 Trial Of PF-04856884 (CVX-060), A Selective Angiopoietin-2 (Ang-2) Binding CovX-body, In Patients With Recurrent Glioblastoma
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Glioblastoma
Keywords: recurrent glioblastoma multiforme (GBM)
CVX-060
PF-04856884
phase 2
open-label
bevacizumab
anti-angiogenic
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2010-10-21
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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Notification of study being cancelled resulted in update in overall status change from "not yet recruiting" to "withdrawn."

Eligibility criteria: 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.

Primary outcomes:
measure: Progression free survival rate at Month 6 (PFS6) defined as the patient progression free status at Month 6.
timeFrame: 1 year
Secondary outcomes:
measure: Corticosteroid doses at baseline and on-study
timeFrame: 4 months
measure: Overall Response Rate (ORR)
timeFrame: 2 years
measure: 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.
timeFrame: 2 years
measure: Time to death is defined as the time from first study drug to death due to any cause.
timeFrame: 2 years
measure: Overall survival (OS) defined as the time from first dose of study drug to death due to any cause.
timeFrame: 2 years
measure: 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.
timeFrame: 2 years
measure: Immunogenicity determined by measuring anti-PF-04856884 antibodies following therapy
timeFrame: 4 months
measure: 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
timeFrame: 4 months
Other outcomes:
Locations:
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: