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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00612339
Recruitment Status : Completed
First Posted : February 11, 2008
Results First Posted : September 10, 2012
Last Update Posted : May 27, 2013
Sponsor:
Collaborators:
Genentech, Inc.
Schering-Plough
Information provided by (Responsible Party):
Duke University

Tracking Information
First Submitted Date  ICMJE January 29, 2008
First Posted Date  ICMJE February 11, 2008
Results First Submitted Date  ICMJE August 9, 2012
Results First Posted Date  ICMJE September 10, 2012
Last Update Posted Date May 27, 2013
Study Start Date  ICMJE August 2007
Actual Primary Completion Date May 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 18, 2012)
Response Rate [ Time Frame: 4 months ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: February 8, 2008)
Response Rate [ Time Frame: 6 months ]
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: February 8, 2008)
  • Progression-free survival [ Time Frame: 6 months ]
  • Incidence & severity of CNS hemorrhage & systemic hemorrhage. Incidence of > gr4 hematologic & > gr3 non-hematologic toxicities [ Time Frame: 6 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Avastin in Combination With Temozolomide for Unresectable or Multifocal GBMs and Gliosarcomas
Official Title  ICMJE Avastin in Combination With Temozolomide for Unresectable or Multifocal Glioblastoma Multiformes and Gliosarcomas
Brief Summary

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

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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Glioblastoma
  • Gliosarcoma
Intervention  ICMJE 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
Study Arms  ICMJE 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.
Intervention: Drug: Avastin and Temozolomide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 8, 2008)
41
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE May 2012
Actual Primary Completion Date May 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00612339
Other Study ID Numbers  ICMJE Pro00001022
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Duke University
Study Sponsor  ICMJE Duke University
Collaborators  ICMJE
  • Genentech, Inc.
  • Schering-Plough
Investigators  ICMJE
Principal Investigator: Katherine B Peters, MD, PhD Duke University Health System
PRS Account Duke University
Verification Date September 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP