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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

Phase 2
18 Years
Open (Enrolling)
Glioblastoma Multiforme

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Trial Information

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

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.

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

- 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.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free Survival (PFS)

Outcome Time Frame:

18 months

Safety Issue:


Principal Investigator

John D Hainsworth, M.D.

Investigator Role:

Study Chair

Investigator Affiliation:

Sarah Cannon Research Institute


United States: Food and Drug Administration

Study ID:




Start Date:

January 2009

Completion Date:

December 2012

Related Keywords:

  • Glioblastoma Multiforme
  • Glioblastoma Multiforme
  • Radiation Therapy
  • Temozolomide
  • Bevacizumab
  • Everolimus
  • Glioblastoma



Florida Cancer Specialists Fort Myers, Florida  33901
Northeast Georgia Medical Center Gainesville, Georgia  30501
Research Medical Center Kansas City, Missouri  64132
Consultants in Blood Disorders and Cancer Louisville, Kentucky  40207
South Carolina Oncology Associates, PA Columbia, South Carolina  29210
Virginia Cancer Institute Richmond, Virginia  23230
Methodist Cancer Center Omaha, Nebraska  68114
Peninsula Cancer Institute Newport News, Virginia  23601
Center for Cancer and Blood Disorders Bethesda, Maryland  20817
Clearview Cancer Institute Huntsville, Alabama  35805
Grand Rapids Clinical Oncology Program Grand Rapids, Michigan  49503
St. Louis Cancer Care Chesterfield, Missouri  63017
Tennessee Oncology, PLLC Clarksville, Tennessee  37043