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

This study has been completed.
Sponsor:
Collaborators:
Genentech, Inc.
Novartis
Information provided by (Responsible Party):
SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier:
NCT00805961
First received: December 9, 2008
Last updated: July 1, 2013
Last verified: August 2012
  Purpose

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 Intervention Phase
Glioblastoma Multiforme
Radiation: Radiation therapy
Drug: Temozolomide
Drug: Bevacizumab
Drug: Everolimus
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by SCRI Development Innovations, LLC:

Primary Outcome Measures:
  • Progression-free Survival (PFS) [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To Assess the Toxicity of This Novel Multimodality Regimen [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
  • To Assess the Overall Survival of Patients With Glioblastoma Multiforme Following Treatment With This Novel Multimodality Regimen [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • To Assess the Complete Response Rate of Patients With Glioblastoma Multiforme Following Treatment With This Novel Multimodality Regimen [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Enrollment: 68
Study Start Date: January 2009
Study Completion Date: May 2013
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

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

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.
  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: NCT00805961

Locations
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.
Novartis
Investigators
Study Chair: John D Hainsworth, M.D. SCRI Development Innovations, LLC
  More Information

Publications:
Responsible Party: SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier: NCT00805961     History of Changes
Other Study ID Numbers: SCRI CNS 10
Study First Received: December 9, 2008
Results First Received: August 22, 2012
Last Updated: July 1, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by SCRI Development Innovations, LLC:
Glioblastoma Multiforme
Radiation Therapy
Temozolomide
Bevacizumab
Everolimus

Additional relevant MeSH terms:
Glioblastoma
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
Everolimus
Sirolimus
Temozolomide
Alkylating Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 20, 2014