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

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.

Condition or disease Intervention/treatment Phase
Glioblastoma Multiforme Radiation: Radiation therapy Drug: Temozolomide Drug: Bevacizumab Drug: Everolimus Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 68 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : January 2009
Actual Primary Completion Date : October 2009
Actual Study Completion Date : May 2013

Arm Intervention/treatment
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

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

Primary Outcome Measures :
  1. Progression-free Survival (PFS) [ Time Frame: 18 months ]

Secondary Outcome Measures :
  1. To Assess the Toxicity of This Novel Multimodality Regimen [ Time Frame: 18 months ]
  2. To Assess the Overall Survival of Patients With Glioblastoma Multiforme Following Treatment With This Novel Multimodality Regimen [ Time Frame: 18 months ]
  3. To Assess the Complete Response Rate of Patients With Glioblastoma Multiforme Following Treatment With This Novel Multimodality Regimen [ Time Frame: 18 months ]

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00805961

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United States, Alabama
Clearview Cancer Institute
Huntsville, Alabama, United States, 35805
United States, Florida
Florida Cancer Specialists
Fort Myers, Florida, United States, 33901
United States, Georgia
Northeast Georgia Medical Center
Gainesville, Georgia, United States, 30501
United States, Kentucky
Consultants in Blood Disorders and Cancer
Louisville, Kentucky, United States, 40207
United States, Maryland
Center for Cancer and Blood Disorders
Bethesda, Maryland, United States, 20817
United States, Michigan
Grand Rapids Clinical Oncology Program
Grand Rapids, Michigan, United States, 49503
United States, Missouri
St. Louis Cancer Care
Chesterfield, Missouri, United States, 63017
Research Medical Center
Kansas City, Missouri, United States, 64132
United States, Nebraska
Methodist Cancer Center
Omaha, Nebraska, United States, 68114
United States, South Carolina
South Carolina Oncology Associates, PA
Columbia, South Carolina, United States, 29210
United States, Tennessee
Tennessee Oncology, PLLC
Nashville, Tennessee, United States, 37023
United States, Virginia
Peninsula Cancer Institute
Newport News, Virginia, United States, 23601
Virginia Cancer Institute
Richmond, Virginia, United States, 23235
Sponsors and Collaborators
SCRI Development Innovations, LLC
Genentech, Inc.
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Study Chair: John D Hainsworth, M.D. SCRI Development Innovations, LLC
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Responsible Party: SCRI Development Innovations, LLC Identifier: NCT00805961    
Other Study ID Numbers: SCRI CNS 10
First Posted: December 10, 2008    Key Record Dates
Results First Posted: September 21, 2012
Last Update Posted: August 28, 2013
Last Verified: August 2012
Keywords provided by SCRI Development Innovations, LLC:
Glioblastoma Multiforme
Radiation Therapy
Additional relevant MeSH terms:
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Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Immunosuppressive Agents
Immunologic Factors
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action