A Trial Of PF-04856884 In Patients With Recurrent Glioblastoma

Glioblastoma Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01225510
• Other study ID #: B1131003
• Status: Withdrawn
• Phase: Phase 2
• First received: October 19, 2010
• Last updated: March 10, 2015
• Start date: January 2011
• Est. completion date: January 2013

Study information

• Verified date: March 2015
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

Description:

Notification of study being cancelled resulted in update in overall status change from "not yet recruiting" to "withdrawn."

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: January 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Glioblastoma

Intervention

Biological:
• PF-04856884
PF-04856884 at a dose of 15 mg/kg/week
• PF-04856884
PF-04856884 at a dose of 15 mg/kg/week

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival rate at Month 6 (PFS6) defined as the patient progression free status at Month 6.		1 year	No
Secondary	Corticosteroid doses at baseline and on-study		4 months	Yes
Secondary	Overall Response Rate (ORR)		2 years	No
Secondary	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	No
Secondary	Time to death is defined as the time from first study drug to death due to any cause.		2 years	No
Secondary	Overall survival (OS) defined as the time from first dose of study drug to death due to any cause.		2 years	No
Secondary	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	No
Secondary	Immunogenicity determined by measuring anti-PF-04856884 antibodies following therapy		4 months	Yes
Secondary	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	No

External Links

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