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RT, Temozolomide, and Bevacizumab Followed by Bevacizumab/Everolimus in First-line Treatment of GBM

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: NCT00805961
Recruitment Status : Completed
First Posted : December 10, 2008
Results First Posted : September 21, 2012
Last Update Posted : August 28, 2013
Sponsor:
Collaborators:
Genentech, Inc.
Novartis
Information provided by (Responsible Party):
SCRI Development Innovations, LLC

Tracking Information
First Submitted Date  ICMJE December 9, 2008
First Posted Date  ICMJE December 10, 2008
Results First Submitted Date  ICMJE August 22, 2012
Results First Posted Date  ICMJE September 21, 2012
Last Update Posted Date August 28, 2013
Study Start Date  ICMJE January 2009
Actual Primary Completion Date October 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 9, 2008)
Progression-free Survival (PFS) [ Time Frame: 18 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT00805961 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 9, 2008)
  • To Assess the Toxicity of This Novel Multimodality Regimen [ Time Frame: 18 months ]
  • To Assess the Overall Survival of Patients With Glioblastoma Multiforme Following Treatment With This Novel Multimodality Regimen [ Time Frame: 18 months ]
  • To Assess the Complete Response Rate of Patients With Glioblastoma Multiforme Following Treatment With This Novel Multimodality Regimen [ Time Frame: 18 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE RT, Temozolomide, and Bevacizumab Followed by Bevacizumab/Everolimus in First-line Treatment of GBM
Official Title  ICMJE A Phase II Study of Concurrent Radiation Therapy, Temozolomide, and Bevacizumab Followed by Bevacizumab/Everolimus in the First-line of Treatment of Patients With Glioblastoma Multiforme
Brief Summary In this phase II trial the investigators plan to incorporate two targeted agents, bevacizumab and everolimus, into the first-line multimodality therapy of glioblastoma. In the first portion of the treatment, bevacizumab will be added to standard concurrent radiation therapy plus temozolomide. After completing radiation therapy, patients will continue treatment with the combination of bevacizumab and everolimus.
Detailed Description Although this maintenance regimen departs from the standard treatment with single agent temozolomide, we feel this approach may add to the overall efficacy of treatment for the following reasons: 1) results with bevacizumab/everolimus in renal cell carcinoma suggest there is at least an additive efficacy when these drugs are used in combination; 2) the efficacy of single agent temozolomide following standard concurrent radiation therapy/temozolomide has not been proven, 3) the use of the three-drug maintenance program (i.e., bevacizumab/everolimus/temozolomide) would probably not be tolerated well on a chronic basis in this patient population; and 4) the bevacizumab/everolimus combination has potential advantages as a maintenance therapy, since it has been well tolerated for many months in patients with other malignancies.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Glioblastoma Multiforme
Intervention  ICMJE
  • Radiation: Radiation therapy
    Radiation therapy, 2.0 Gy daily, 5 days per week by single daily dose, to a total of 60 Gy over 6 weeks
    Other Name: Combined Modality Treatment
  • Drug: Temozolomide
    Temozolomide 75mg/m2 by mouth daily, beginning day 1 of radiation therapy and continuing through the last day of radiation therapy
    Other Name: Combined Modality Treatment
  • Drug: Bevacizumab
    Bevacizumab 10mg/kg IV, every 2 weeks, beginning day 1 of radiation therapy
    Other Name: Combined Modality Treatment
  • Drug: Bevacizumab
    Bevacizumab 10mg/kg IV, every 2 weeks, beginning Week 11
    Other Name: Systemic Therapy
  • Drug: Everolimus
    Everolimus 10mg by mouth daily, beginning Week 11
    Other Name: Systemic Therapy
Study Arms  ICMJE Experimental: Intervention

Combined Modality Treatment and Systemic Therapy

Combined Modality Therapy - Radiation Therapy: 2 Gy/fraction, single daily fractions Monday-Friday, to total of 60 Gy Temozolomide: 75 mg/m2 by mouth daily Bevacizumab: 10 mg/kg IV every 2 weeks (Weeks 1, 3, 5, and 7)

After the last dose of radiation, patients exhibiting an objective response, stable disease on MRI scan, or have stable/improved tumor-related symptoms will begin systemic therapy

Systemic Therapy - Bevacizumab: 10 mg/kg IV every 2 weeks Everolimus: 10 mg by mouth daily

Interventions:
  • Radiation: Radiation therapy
  • Drug: Temozolomide
  • Drug: Bevacizumab
  • Drug: Bevacizumab
  • Drug: Everolimus
Publications * Hainsworth JD, Shih KC, Shepard GC, Tillinghast GW, Brinker BT, Spigel DR. Phase II study of concurrent radiation therapy, temozolomide, and bevacizumab followed by bevacizumab/everolimus as first-line treatment for patients with glioblastoma. Clin Adv Hematol Oncol. 2012 Apr;10(4):240-6.

*   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: August 22, 2012)
68
Original Estimated Enrollment  ICMJE
 (submitted: December 9, 2008)
60
Actual Study Completion Date  ICMJE May 2013
Actual Primary Completion Date October 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age >=18 years.
  • Histologically confirmed intracranial glioblastoma multiforme (WHO grade 4).
  • Patients who have had partial or complete surgical debulking are eligible, as are those with inoperable glioblastoma.
  • No previous treatment with radiotherapy or systemic therapy. Local therapy with a Gliadel wafer placed at the time of surgical debulking is permitted.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Adequate bone marrow function
  • Adequate liver function:
  • Serum creatinine <=1.5 x institutional ULN.
  • Ability to swallow whole pills.
  • Women of child-bearing potential must have a negative serum pregnancy test performed within 7 days prior to start of treatment. Women of child-bearing potential and men must agree to use adequate contraception (barrier method of birth control) while receiving study treatment and for 6 months after the last study treatment. Hormonal contraceptives are not acceptable as a sole method of contraception. Female patients must not breast feed.
  • INR <1.3 or PT/PTT within normal limits in patients not receiving anticoagulation. However, patients receiving anticoagulation treatment with an agent such as warfarin or heparin are also eligible. For patients on warfarin, the INR should be measured prior to initiation of everolimus and monitored at least weekly, or as defined by the local standard of care, until INR is stable.
  • Fasting serum cholesterol <=300 mg/dL OR <=7.75 mmol/L AND fasting triglycerides <= 2.5 x institutional ULN.

Exclusion Criteria:

  • New York Heart Association (NYHA) grade II or greater congestive heart failure (see Appendix B) or symptomatic congestive heart failure.
  • Inadequately controlled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg).
  • History of myocardial infarction or unstable angina within 6 months prior to beginning study treatment.
  • History of stroke or transient ischemic attack within 6 months prior to beginning study treatment.
  • Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to beginning study treatment.
  • Prior history of hypertensive crisis or hypertensive encephalopathy.
  • History of hemoptysis (>=1/2 teaspoon of bright red blood per episode) within 1 month prior to beginning study treatment.
  • Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation).
  • History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1.
  • Serious, non-healing wound, active ulcer, or untreated bone fracture.
  • Proteinuria as demonstrated by urine dipstick for proteinuria >=2+. For patients with >=2+ proteinuria on dipstick urinalysis, a urine protein: creatinine (UPC) ratio will be determined or a 24-hour urine collection will be done. Patients with a UPC ratio <1 or a 24-hour urine protein <1 gram are eligible.
  • Minor surgical procedures (excluding placement of a vascular access device), fine-needle aspirations, or core biopsies within 7 days prior to starting treatment.
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to starting protocol treatment or anticipation of need for major surgical procedure during the course of study treatment. Patients who have not recovered from the side effects of any major surgery are not eligible.
  • Treatment with any investigational agents within 4 weeks of study entry.
  • Chronic, systemic treatment with corticosteroids or other immunosuppressive agents. Topical or inhaled steroids are allowed.
  • Other malignancies within the past 3 years except for adequately treated carcinoma in situ of the cervix or basal cell or superficial squamous (skin cell) carcinomas.
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 NCT00805961
Other Study ID Numbers  ICMJE SCRI CNS 10
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party SCRI Development Innovations, LLC
Study Sponsor  ICMJE SCRI Development Innovations, LLC
Collaborators  ICMJE
  • Genentech, Inc.
  • Novartis
Investigators  ICMJE
Study Chair: John D Hainsworth, M.D. SCRI Development Innovations, LLC
PRS Account SCRI Development Innovations, LLC
Verification Date August 2012

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