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Hypofractionated Intensity-Modulated Radiation Therapy With Temozolomide and Bevacizumab for Glioblastoma Multiforme

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ClinicalTrials.gov Identifier: NCT01209442
Recruitment Status : Completed
First Posted : September 27, 2010
Last Update Posted : June 12, 2017
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
University of Colorado, Denver

Tracking Information
First Submitted Date  ICMJE September 23, 2010
First Posted Date  ICMJE September 27, 2010
Last Update Posted Date June 12, 2017
Actual Study Start Date  ICMJE September 16, 2010
Actual Primary Completion Date September 7, 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 24, 2010)
6-month progression-free survival [ Time Frame: 6 months ]
To use 6-month progression-free survival to assess the efficacy of the combination of hypofractionated IMRT delivering 60 Gy over 2 weeks with concurrent bevacizumab and temozolomide followed by 6 cycles of adjuvant bevacizumab and temozolomide.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01209442 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 24, 2010)
Overall survival, measured from the day of initial diagnosis (biopsy or surgery) to the time of death from any cause. [ Time Frame: follow up for life ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE Hypofractionated Intensity-Modulated Radiation Therapy With Temozolomide and Bevacizumab for Glioblastoma Multiforme
Official Title  ICMJE A Pilot Phase II Trial of Hypofractionated Intensity-Modulated Radiation Therapy (Hypo-IMRT) Combining With Temozolomide (TMZ) and Bevacizumab for Patients With Newly Diagnosed Glioblastoma Multiforme (GBM)
Brief Summary The purpose of this study is to find out whether Hypofractionated Intensity-Modulated Radiation Therapy (Hypo-IMRT) combining with temozolomide chemotherapy can be safely given with a targeted agent, bevacizumab, and how effective this study treatment will be in controlling your brain tumor.
Detailed Description This is a pilot phase II trial of the combination of concurrent hypofractionated IMRT (60 Gy/2 weeks), temozolomide and bevacizumab followed by 6 cycles of adjuvant bevacizumab and temozolomide in patients with grade IV malignant gliomas (glioblastoma and gliosarcoma). The study will have survival and toxicity endpoints.
Study Type  ICMJE Interventional
Study Phase Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Glioblastoma Multiforme
Intervention  ICMJE
  • Drug: Bevacizumab
    Bevacizumab will be administered at 10 mg/kg on day 1 and day 15. Four to six weeks following completion of concurrent IMRT, TMZ and bevacizumab, patients will receive 6 cycles of Bevacizumab.
    Other Name: Avastin
  • Drug: Temozolomide
    Patients will be treated with hypofractionated IMRT (60 Gy in 10 Fx) and daily temozolomide at 75 mg/m2 qd concurrent with IMRT. Four to six weeks following completion of concurrent IMRT, TMZ and bevacizumab, temozolomide will be given at 150-200 mg/m2 qd on days 1-5 of each cycle.
    Other Name: Temodar
  • Radiation: RT (Radiation Therapy)
    Patients will be treated with hypofractionated IMRT (60 Gy in 10 Fx)
Study Arms Experimental: RT with Temozolomide and Bevacizumab
Patients will be treated with hypofractionated IMRT (60 Gy in 10 Fx) and daily TMZ at 75 mg/m2 qd concurrent with IMRT (including weekends and holidays). Bevacizumab will be administered at 10 mg/kg on day 1 and day 15. Day 1 and the 1st Fx of IMRT must start on the same day. Four to six weeks following completion of concurrent IMRT, TMZ and bevacizumab therapy, patients will have a brain MRI and if there is no evidence of disease progression, patients will receive 6 cycles of Bevacizumab and TMZ. Beginning a minimum of 28 days after the last radiation treatment the bevacizumab will be dosed at 10 mg/kg on day 1 and day 15 of each cycle. TMZ will be given at 150-200 mg/m2 qd on days 1-5 of each cycle. Each cycle is 28 days.
Interventions:
  • Drug: Bevacizumab
  • Drug: Temozolomide
  • Radiation: RT (Radiation Therapy)
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: May 28, 2013)
30
Original Estimated Enrollment  ICMJE
 (submitted: September 24, 2010)
35
Actual Study Completion Date February 3, 2017
Actual Primary Completion Date September 7, 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically confirmed diagnosis of WHO grade IV primary malignant glioma (GBM or gliosarcoma).
  • Age ≥ 18 years at the time of study registration
  • Karnofsky Performance Scale ≥ 60%
  • Absolute Neutrophil Count (ANC) ≥ 1,500 cells/mm3, hemoglobin ≥ 9.0 g/dl, platelets ≥ 100,000 cells/ mm3
  • Serum creatinine ≤ 1.5 mg/dl, serum glutamate oxaloacetate transaminase (SGOT) and bilirubin ≤ 1.5 times upper limit of normal
  • Signed informed consent approved by the Institutional Review Board
  • Craniotomy or intracranial biopsy site must be adequately healed, free of drainage or cellulitis, and the underlying cranioplasty must appear intact at the time of study entry. Study treatment should be initiated > 28 days following the last surgical procedure (including open biopsy, surgical resection, wound revision, or any other major surgery involving entry into a body cavity)

Exclusion Criteria:

  • Life expectancy of less than 12 weeks
  • Prior treatment, including radiation therapy or chemotherapy, for GBM with the exception of surgery (Gliadel Wafers are allowed at the time of surgery)
  • Active malignancy, with the exception of superficial basal cell and/or superficial squamous (skin) cell, or carcinoma in situ of the cervix
  • Active infection requiring IV antibiotics
  • Pregnant or breast feeding
  • International normalized ratio (INR) > 1.5 and activated partial thromboplastin time (aPTT) > 1.5 × the upper limit of normal (ULN) (except for subjects receiving anticoagulation therapy) in the absence of therapeutic intent to anticoagulate the subject. Therapeutic anticoagulation is permitted
  • Evidence of ≥ Common Toxicity Criteria for Adverse Effects (CTCAE) v.3 grade 2 CNS hemorrhage (CNS hemorrhage when medical intervention indicated), but grade 1 CNS hemorrhage (asymptomatic radiographic findings on the baseline brain CT or MRI only) is allowed. Punctate hemorrhage or the presence of hemosiderin is not considered a Grade 1 event for the purpose of this study. )
  • Inadequately controlled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure > 100 mmHg)
  • Prior history of hypertensive crisis or hypertensive encephalopathy
  • Current New York Heart Association (NYHA) Grade II or greater congestive heart failure
  • History of myocardial infarction or unstable angina within 6 months prior to enrollment
  • History of stroke or transient ischemic attack within 6 months prior to enrollment
  • Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to enrollment
  • History of hemoptysis (≥ 1/2 teaspoon of bright red blood per episode) within 1 month prior to enrollment
  • Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to enrollment or anticipation of need for major surgical procedure during the course of the study
  • Core needle biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to enrollment
  • History of abdominal fistula or gastrointestinal perforation within 6 months prior to enrollment
  • Serious, non-healing wound, active ulcer, or untreated bone fracture
  • Proteinuria as demonstrated by a Urine protein-creatinine ratios (UPC) ratio ≥ 1.0 at screening (Appendix A).
  • Known hypersensitivity to any component of bevacizumab
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers 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 NCT01209442
Other Study ID Numbers  ICMJE 10-0274.cc
AVF4733s ( Other Grant/Funding Number: Genentech, Inc )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party University of Colorado, Denver
Study Sponsor  ICMJE University of Colorado, Denver
Collaborators  ICMJE Genentech, Inc.
Investigators  ICMJE
Principal Investigator: Douglas Ney, M.D University of Colorado, Denver
PRS Account University of Colorado, Denver
Verification Date June 2017

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