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

NCT00805961 | Completed Phase 2 Results

• 1 other identifier: SCRI CNS 10
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 13

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.

Conditions

Glioblastoma Multiforme

Keywords

Glioblastoma Multiforme; Radiation Therapy; Temozolomide; Bevacizumab; Everolimus

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS)

  Progression-free survival is defined as the duration of time from start of treatment to time of progression or death, whichever comes first.

  18 months

Secondary Outcomes (3)

• Number of Participants Experiencing Toxicity After This Novel Multimodality Regimen

  18 months

• Overall Survival of Patients With Glioblastoma Multiforme Following Treatment With This Novel Multimodality Regimen

  18 months

• Objective Response Rate of Patients With Glioblastoma Multiforme Following Treatment With This Novel Multimodality Regimen

  18 months

Study Arms (1)

Intervention

EXPERIMENTAL

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; Drug: Temozolomide; Drug: Bevacizumab; Drug: Everolimus

Interventions

Radiation therapy RADIATION

Radiation therapy, 2.0 Gy daily, 5 days per week by single daily dose, to a total of 60 Gy over 6 weeks

Also known as: Combined Modality Treatment

Intervention

Temozolomide DRUG

Temozolomide 75mg/m2 by mouth daily, beginning day 1 of radiation therapy and continuing through the last day of radiation therapy

Also known as: Combined Modality Treatment

Intervention

Bevacizumab DRUG

Bevacizumab 10mg/kg IV, every 2 weeks, beginning day 1 of radiation therapy

Also known as: Combined Modality Treatment

Intervention

Everolimus DRUG

Everolimus 10mg by mouth daily, beginning Week 11

Also known as: Systemic Therapy

Intervention

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• SCRI Development Innovations, LLC: lead
• Genentech, Inc.: collaborator
• Novartis: collaborator

Study Sites (13)

Clearview Cancer Institute

Huntsville, Alabama, 35805, United States

Location

Florida Cancer Specialists

Fort Myers, Florida, 33901, United States

Location

Northeast Georgia Medical Center

Gainesville, Georgia, 30501, United States

Location

Consultants in Blood Disorders and Cancer

Louisville, Kentucky, 40207, United States

Location

Center for Cancer and Blood Disorders

Bethesda, Maryland, 20817, United States

Location

Grand Rapids Clinical Oncology Program

Grand Rapids, Michigan, 49503, United States

Location

St. Louis Cancer Care

Chesterfield, Missouri, 63017, United States

Location

Research Medical Center

Kansas City, Missouri, 64132, United States

Location

Methodist Cancer Center

Omaha, Nebraska, 68114, United States

Location

South Carolina Oncology Associates, PA

Columbia, South Carolina, 29210, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37023, United States

Location

Peninsula Cancer Institute

Newport News, Virginia, 23601, United States

Location

Virginia Cancer Institute

Richmond, Virginia, 23235, United States

Location

Related Publications (1)

• 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.

  PMID: 22706484 BACKGROUND

MeSH Terms

Conditions

Glioblastoma

Interventions

Radiotherapy; Combined Modality Therapy; Temozolomide; Bevacizumab; Everolimus

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Therapeutics; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sirolimus; Macrolides; Lactones

Results Point of Contact

• Title: John D. Hainsworth, MD.
• Organization: Sarah Cannon Research Institute

ASKSARAH@scresearch.net

877-691-7274

Study Officials

• John D Hainsworth, M.D.

  SCRI Development Innovations, LLC

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2008
• First Posted: December 10, 2008
• Study Start: January 1, 2009
• Primary Completion: October 1, 2009
• Study Completion: May 1, 2013
• Last Updated: December 8, 2021
• Results First Posted: September 21, 2012

Record last verified: 2021-11

Locations

US (13)