A Trial Of PF-04856884 In Patients With Recurrent Glioblastoma

This study has been withdrawn prior to enrollment.
Sponsor:
Information provided by:
Pfizer
ClinicalTrials.gov Identifier:
NCT01225510
First received: October 19, 2010
Last updated: December 22, 2010
Last verified: December 2010
  Purpose

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).


Condition Intervention Phase
Glioblastoma
Biological: PF-04856884
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Progression free survival rate at Month 6 (PFS6) defined as the patient progression free status at Month 6. [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Corticosteroid doses at baseline and on-study [ Time Frame: 4 months ] [ Designated as safety issue: Yes ]
  • Overall Response Rate (ORR) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Time to death is defined as the time from first study drug to death due to any cause. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Overall survival (OS) defined as the time from first dose of study drug to death due to any cause. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Immunogenicity determined by measuring anti-PF-04856884 antibodies following therapy [ Time Frame: 4 months ] [ Designated as safety issue: Yes ]
  • 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 [ Time Frame: 4 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: January 2011
Estimated Study Completion Date: January 2013
Estimated Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Primary Cohort Biological: PF-04856884
PF-04856884 at a dose of 15 mg/kg/week
Other Name: CVX-060
Experimental: Exploratory Cohort Biological: PF-04856884
PF-04856884 at a dose of 15 mg/kg/week
Other Name: CVX-060

Detailed Description:

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01225510

Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Director, Clinical Trial Disclosure Group, Pfizer, Inc.
ClinicalTrials.gov Identifier: NCT01225510     History of Changes
Other Study ID Numbers: B1131003
Study First Received: October 19, 2010
Last Updated: December 22, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
recurrent glioblastoma multiforme (GBM)
CVX-060
PF-04856884
phase 2
open-label
bevacizumab
anti-angiogenic

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors

ClinicalTrials.gov processed this record on October 23, 2014