Phase II Avastin + Bortezomib for Patients With Recurrent Malignant Glioma

NCT00611325 | Completed Phase 2 Results DMC

• 1 other identifier: Pro00003596
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

Primary Objective To estimate 6-month progression free survival probability of patients with recurrent glioblastoma multiforme treated with bortezomib plus Avastin. This efficacy assessment will be made separately among patients on enzyme-inducing anti-epileptic drugs and non enzyme-inducing anti-epileptic drugs. Secondary Objectives To evaluate safety \& tolerability of bortezomib plus Avastin among patients with recurrent malignant glioma. To evaluate radiographic response, progression free survival \& overall survival of patients with recurrent malignant glioma treated with bortezomib plus Avastin

Conditions

Glioblastoma; Gliosarcoma

Keywords

Glioblastoma; Gliosarcoma; Glioblastoma multiforme; Recurrent malignant glioma; GBM; Recurrent GBM; Malignant glioma; Brain tumor; Avastin; Bevacizumab; Bortezomib; Velcade

Outcome Measures

Primary Outcomes (1)

• 6-month Progression-free Survival (PFS)

  Percentage of participants surviving six months from the initiation of treatment without progression of disease. PFS was defined as the time from the initiation of treatment to the date of the first documented progression according to the Macdonald criteria, or to death due to any cause. Per Macdonald, progression is a ≥ 25% increase in the sum of the products of perpendicular diameters of enhancing lesions, any new lesion or clinical deterioration.

  6 months

Secondary Outcomes (4)

• Median Progression Free Survival (PFS)

  Time in months from the start of study treatment to the date of first progression or death. Assessed up to 60 months.

• Median Overall Survival (OS)

  Time in months from the start of study treatment to date of death due to any cause. Assessed up to 60 months.

• Radiographic Response Rate

  60 months

• Number of Patients With Grade 3 or Greater, Treatment-related, Non-hematologic Toxicities

  60 months

Study Arms (2)

EIAED

EXPERIMENTAL

Patients taking enzyme-inducing anti-epileptic drugs (EIAEDs). Avastin was administered intravenously at a dose of 15 mg/kg every 3 weeks. Bortezomib was adminstered intravenously at a dose of 2.5 mg/m2 on days 1, 4, 8, 11, 22, 25, 29, and 32 of a 42-day cycle.

Drug: Avastin; Drug: Bortezomib

Non-EIAED

EXPERIMENTAL

Patients not taking enzyme-inducing anti-epileptic drugs (EIAEDs). Avastin was administered intravenously at a dose of 15 mg/kg every 3 weeks. Bortezomib was adminstered intravenously at a dose of 1.7 mg/m2 on days 1, 4, 8, 11, 22, 25, 29, and 32 of a 42-day cycle.

Drug: Avastin; Drug: Bortezomib

Interventions

Avastin DRUG

Avastin was administered intravenously at the dose 15 mg/kg every 3 weeks.

Also known as: Bevacizumab

EIAED; Non-EIAED

Bortezomib DRUG

Bortezomib was administered on days 1, 4, 8, 11, 22, 25, 29, \& 32 of a 42-day cycle. Bortezomib was 1.7 mg/m2 for patients not taking EIAEDs \& 2.5 mg/m2 for patients taking EIAEDs.

Also known as: Velcade

EIAED; Non-EIAED

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients have histologically confirmed diagnosis of recurrent/progressive WHO grade IV malignant glioma (MG)
• Age \>18 yrs
• No prior treatment with bortezomib, \& no Avastin in last 3 months, not allowed to have progressed to Avastin regimen. No history of \> or equal to grade 2 CNS hemorrhage or grade 3 or higher toxicities while on Avastin
• At least 6 weeks from surgical resection, 4 weeks from end of radiotherapy \& enrollment in this study
• Karnofsky Performance Status (KPS) \> or equal to 70%
• Hemoglobin (Hgb) \> or = to 9 g/deciliter (dL), absolute neutrophil count (ANC) \> or = to 1,500 cells/microliter, platelets \> or = to 125,000 cells/microliter;
• Serum creatinine \<1.5 mg/dL, serum glutamic oxalocetic transaminase (SGOT) \& bilirubin \<1.5 x upper limit of normal
• Signed informed consent approved by IRB;
• If sexually active, patients must agree to take contraceptive measures for duration of treatments
• May have had up to 3 biological therapies (such as tyrosine kinase inhibitors, topoisomerase I or II inhibitors, or rapamycin)

You may not qualify if:

• Gr 2 or greater peripheral neuropathy at time of study enrollment
• No prior taxanes, as it predisposes to sensory neuropathy
• Co-medication that may interfere with study results, e.g. immuno-suppressive agents other than corticosteroids
• Greater than 3 prior recurrences
• Evidence of CNS hemorrhage on baseline MRI on CT scan (except for grade 1 hemorrhage that has been stable for at least 3 months)
• History of thrombotic or hemorrhagic stroke or myocardial infarction within 6 months
• Requires therapeutic anti-coagulation
• At least 4 weeks from Day 0 of prior monthly chemotherapy (at least 6 weeks if a nitrosourea). At least 1 week from last dose of daily chemotherapy (such as metronomic temozolomide, cytoxan) or targeted therapies administered daily (such as gleevec, tarceva)
• Pregnancy or breast feeding
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring IV antibiotics \& psychiatric illness/social situations that would limit compliance with study requirements, or disorders associated with significant immunocompromised state
• Patients with another primary malignancy that has required treatment within past year.
• Avastin-Specific Concerns:
• Any prior history of hypertensive crisis or hypertensive encephalopathy
• Systolic blood pressure (BP) \> 150 mmHg or diastolic BP \> 100 mmHg
• Unstable angina

Sponsors & Collaborators

• Duke University: lead
• Millennium Pharmaceuticals, Inc.: collaborator
• Genentech, Inc.: collaborator

Study Sites (1)

Duke University Health System

Durham, North Carolina, 27710, United States

Location

Related Links

• The Preston Robert Tisch Brain Tumor Center at DUKE

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma; Glioma; Brain Neoplasms

Interventions

Bevacizumab; Bortezomib

Condition Hierarchy (Ancestors)

Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Katherine B. Peters
• Organization: Duke University Medical Center

katherine.peters@duke.edu

(919) 684-6173

Study Officials

• Katherine B Peters, MD

  Duke Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2008
• First Posted: February 8, 2008
• Study Start: May 1, 2008
• Primary Completion: September 1, 2009
• Study Completion: October 1, 2013
• Last Updated: March 12, 2014
• Results First Posted: February 4, 2014

Record last verified: 2014-02

Locations

US (1)