A Trial Of PF-04856884 In Patients With Recurrent Glioblastoma

A Phase 2 Trial Of PF-04856884 (CVX-060), A Selective Angiopoietin-2 (Ang-2) Binding CovX-body, In Patients With Recurrent Glioblastoma

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).

Study Overview

• Status: Withdrawn
• Conditions: Glioblastoma
• Intervention / Treatment: Biological: PF-04856884

Detailed Description

Notification of study being cancelled resulted in update in overall status change from "not yet recruiting" to "withdrawn."

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Primary Cohort	Biological: PF-04856884; PF-04856884 at a dose of 15 mg/kg/week; Other Names: CVX-060
Experimental: Exploratory Cohort	Biological: PF-04856884; PF-04856884 at a dose of 15 mg/kg/week; Other Names: CVX-060

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression free survival rate at Month 6 (PFS6) defined as the patient progression free status at Month 6.	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall Response Rate (ORR)	2 years
Corticosteroid doses at baseline and on-study	4 months
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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Anticipated): January 1, 2013
• Study Completion (Anticipated): January 1, 2013

Study Registration Dates

• First Submitted: October 19, 2010
• First Submitted That Met QC Criteria: October 19, 2010
• First Posted (Estimate): October 21, 2010

Study Record Updates

• Last Update Posted (Estimate): March 11, 2015
• Last Update Submitted That Met QC Criteria: March 10, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: bevacizumab; open-label; phase 2; anti-angiogenic; CVX-060; PF-04856884; recurrent glioblastoma multiforme (GBM)
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma
• Other Study ID Numbers: B1131003