Avastin in Combination With Temozolomide for Unresectable or Multifocal GBMs and Gliosarcomas

This study has been completed.
Sponsor:
Collaborators:
Genentech, Inc.
Schering-Plough
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT00612339
First received: January 29, 2008
Last updated: May 20, 2013
Last verified: September 2012
  Purpose

Primary objective- To determine efficacy of Avastin, 10 mg/kg every other week, in combination with standard 5-day temozolomide in terms of response rate.

Secondary objective- To determine safety of Avastin & Temozolomide in unresectable glioblastoma patients


Condition Intervention Phase
Glioblastoma
Gliosarcoma
Drug: Avastin and Temozolomide
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Avastin in Combination With Temozolomide for Unresectable or Multifocal Glioblastoma Multiformes and Gliosarcomas

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Response Rate [ Time Frame: 4 months ] [ Designated as safety issue: No ]
    The proportion of subjects with complete or partial response as determined by a modification of the RANO (Response Assessment in Neuro-Oncology) criteria. A confirmation of response was not required. Complete Response was defined as complete disappearance on MR/CT of all enhancing tumor and mass effect, off all corticosteroids (or receiving only adrenal replacement doses), accompanied by a stable or improving neurologic examination, and maintained for at least 4 weeks. Partial Response was defined as greater than or equal to 50% reduction in tumor size on MR/CT by bi-dimensional measurement, on a stable or decreasing dose of corticosteroids, accompanied by a stable or improving neurologic examination, and maintained for at least 4 weeks.


Enrollment: 41
Study Start Date: August 2007
Study Completion Date: May 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Avastin and Temozolomide
Avastin administered at 10 mg/kg every 2 weeks beginning a minimum of 7 days after biopsy or 28 days after craniotomy. Temozolomide dosed at 200 mg/m2 daily for 5 days in a 28-day cycle.
Drug: Avastin and Temozolomide
This is Phase II study with the combination of Avastin & Temozolomide for unresectable or multifocal WHO grade IV malignant glioma patients. Patients will receive up to 4 cycles of Avastin & Temozolomide . Avastin administered at 10 mg/kg every 14 days beginning minimum of 7 days after biopsy or 28 days after craniotomy. Temozolomide will be dosed at 200 mg/m2 daily x 5 days in 28-day cycle. Patients will have baseline MRI & repeat MRI every 4 weeks. If there is no evidence of disease progression after each cycle, or unacceptable toxicity, or as determined by investigators, patient non-compliance or patient withdraws consent to continue therapy & requests discontinuation, patients will receive up to 4 cycles of Avastin & Temozolomide, then proceed with standard XRT therapy, & future therapy after 4 cycles will be at discretion of patient & treating physicians.
Other Names:
  • Avastin - Bevacizumab
  • Temozolomide - Temodar

Detailed Description:

Subjects have histologically confirmed WHO gr IV primary malignant glioma that is unresectable/multifocal. This is Phase II study where up to 41 subjects will receive up to 4 cycles of Avastin & Temozolomide. Avastin administered at 10 mg/kg every 14 days beginning a minimum of 7 days after biopsy/28 days after craniotomy. Temozolomide dosed at 200 mg/m2 daily for 5 days in 28-day cycle. Patients will receive up to 4 cycles of Avastin & Temozolomide, then proceed with standard XRT. Study will use 2-stage "minimax" study design in which 21 subjects are accrued during 1st stage, with possibility that additional 20 patients accrued during 2nd stage. In initial Phase I & II trials, 4 potential Avastin-associated safety signals were identified: hypertension, proteinuria, thromboembolic events, & hemorrhage. Avastin-associated adverse events in Phase III trials include congestive heart failure, GI perforations, wound healing complications, & arterial thromboembolic events. Most common toxicity associated with Temozolomide has been mild myelosuppression.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Patients have histologically confirmed diagnosis of WHO gr IV primary malignant glioma. Patients will be unresectable or have multifocal disease.

  • Age ≥ 18years & life expectancy of >12 weeks
  • Evidence of measurable primary CNS neoplasm on contrast enhanced MRI.
  • Interval of <1 week between prior biopsy/4 weeks from surgical resection & enrollment on protocol
  • Karnofsky ≥60%
  • Hemoglobin ≥9g/dl, ANC ≥1,500 cells/microliter, platelets ≥125,000 cells/microliter
  • Serum creatinine ≤1.5 mg/dl, serum SGOT & bilirubin ≤1.5 x ULN
  • For patients on corticosteroids, they must have been on stable dose for 1 week prior to entry, if clinically possible, & dose should not be escalated over entry dose level
  • Signed informed consent approved by IRB prior to patient entry
  • No evidence of > grade 1 CNS hemorrhage on baseline MRI/CT scan
  • If sexually active, patients will take contraceptive measures for duration of treatments

Exclusion Criteria:

  • Pregnancy/breast feeding
  • Co-medication that may interfere with study results
  • Active infection requiring IV antibiotics
  • Prior or current Treatment w XRT/chemo for brain tumor, irrespective of grade of tumor
  • Evidence of > grade 1 CNS hemorrhage on baseline MRI or CT scan

Avastin-Specific Concerns:

  • Inadequately controlled hypertension
  • Any prior history of hypertensive crisis/hypertensive encephalopathy
  • New York Heart Association Grade II or > congestive heart failure
  • History of myocardial infarction/unstable angina < 6 months prior to study enrollment
  • History of stroke/transient ischemic attack < 6 months prior to study enrollment
  • Significant vascular disease
  • Symptomatic peripheral vascular disease
  • Evidence of bleeding diathesis/coagulopathy
  • Major surgical procedure, open biopsy,/significant traumatic injury within 28 days prior to study enrollment/anticipation of need for major surgical procedure during course of study
  • Core biopsy/other minor surgical procedure, excluding placement of vascular access device, <7 days prior to study enrollment
  • History of abdominal fistula, GI perforation, /intra-abdominal abscess <6 months prior to study enrollment
  • Serious, non-healing wound, ulcer, or bone fracture
  • Proteinuria at screening as demonstrated by either
  • UPC ratio ≥1.0 at screening OR
  • Urine dipstick for proteinuria ≥2+
  • Known hypersensitivity to any component of Avastin
  • Pregnant/lactating. Use of effective means of contraception in subjects of child-bearing potential
  • Current, ongoing treatment with full-dose warfarin or its equivalent
  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: NCT00612339

Locations
United States, North Carolina
Duke University Health System
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Duke University
Genentech, Inc.
Schering-Plough
Investigators
Principal Investigator: Katherine B Peters, MD, PhD Duke University Health System
  More Information

Additional Information:
No publications provided

Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT00612339     History of Changes
Other Study ID Numbers: Pro00001022
Study First Received: January 29, 2008
Results First Received: August 9, 2012
Last Updated: May 20, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Duke University:
Glioma
Temozolomide
Temodar
Avastin
Bevacizumab
GBM
Gliosarcoma
Multifocal GBM
Brain tumor
Unresectable GBM
Glioblastoma multiforme

Additional relevant MeSH terms:
Glioblastoma
Gliosarcoma
Astrocytoma
Glioma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Bevacizumab
Dacarbazine
Temozolomide
Alkylating Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Growth Inhibitors
Growth Substances
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014