Bevacizumab and Irinotecan or Temozolomide in Treating Patients With Recurrent or Refractory Glioblastoma Multiforme or Gliosarcoma

NCT00433381 | Completed Phase 2 Results

• 6 other identifiers: NCI-2009-00743RTOG-0625ACRIN-6677CDR0000528259RTOG 0625U10CA021661
• Study Type: interventional
• Target: 123
• Locations: 1 country
• Sites: 93

Brief Summary

This randomized phase II trial is studying the side effects and how well giving bevacizumab together with irinotecan or temozolomide works in treating patients with recurrent or refractory glioblastoma multiforme or gliosarcoma. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Drugs used in chemotherapy, such as irinotecan and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab together with irinotecan or temozolomide may kill more tumor cells.

Conditions

Adult Glioblastoma; Adult Gliosarcoma; Recurrent Adult Brain Neoplasm

Outcome Measures

Primary Outcomes (4)

• Count/Percentage of Patients Progression-free at 6 Months for Bevacizumab and Irinotecan Hydrochloride Arm

  Progression defined as ≥ 25% increase in the size of enhancing tumor or any new tumor; or neurologically worse, and steroids stable or increased. Percentage is calculated by taking the number of patients who have survived 6 months without progression of study disease after study registration in the numerator. The denominator consists of all patients except those who were found retrospectively to be ineligible or who were lost to follow-up after less than 6 months.

  From randomization to six months.

• Count/Percentage of Patients Discontinuing Treatment Due to Treatment-related Medical Complications(Bevacizumab and Temozolomide Arm)

  This endpoint determines tolerability of this treatment arm. If tolerable, then the secondary endpoint of treatment efficacy for this arm occurs. Percentage is calculated by taking the number of patients who did not stop bevacizumab and temozolomide treatment due to medical complications in the numerator. The denominator consists of all patients except those who were found retrospectively to be ineligible or who did not begin treatment.

  From randomization to end of treatment (treatment can continue up to 24 months for patients with stable or responding tumor).

• Number of Participants With Predicted Progression-free Survival at 6 Months (PFS-6)

  Magnetic Resonance Imaging with Spectroscopy (MRS or MRSI) metabolic tumor ratios will be used to predict 6-month progression-free survival (PFS-6) over all study participants. Ratios of NAA/Cho, Cho/Cr, NAA/Cr measured at 2 weeks and 8 weeks and every 2 months until 96wks were used to predict survival, and time to progression, evaluated at 96wks, is the determinate of PFS at 6months (PFS-6). Subjects will not be analyzed by arm.

  2 and 8 weeks posttreatment, and every 2 months until 96wks

• Number of Participants With Predicted Overall Survival (OS) at 12 Months

  Magnetic Resonance Imaging with Spectroscopy (MRS or MRSI) metabolic tumor ratios will be used to predict 12-month overall survival (OS). Ratios of NAA/Cho, Cho/Cr, NAA/Cr measured at 2 weeks and 8 weeks and every 2 months until 96wks were used to predict survival, and time to death, evaluated at 96wks, is the determinate of OS at 12 months. Subjects will not be analyzed by arm.

  2 and 8 weeks posttreatment, and every 2 months until 96wks

Secondary Outcomes (10)

• Count/Percentage of Patients Progression-free at 6 Months for Bevacizumab and Temozolomide Arm

  From randomization to six months.

• Patients' Best Objective Response (Complete Response, Partial Response, Stable Disease, Progression)

  From randomization to death or last follow-up. Patients were followed up to 62.9 months.

• Agreement Between Local Interpretation and Central Interpretation of Standard MRI

  baseline visit, week 2, after every 2 cycles of treatment, and at termination of treatment

• Accuracy of Local PFS 6-mo Interpretation Using Central Review PFS-6 as the Reference Standard

  baseline visit, week 2, after every 2 cycles of treatment, and at termination of treatment

• Correlation of Degree of Cerebral Blood Volume (CBV) and Lactate (Lac) to N-acetylaspartate (NAA) (Lac/NAA) Ratio

  2 weeks following initiation of protocol treatment (T1) and at 8 weeks following chemotherapy with bevacizumab (T2)

Study Arms (2)

Arm I (bevacizumab and temozolomide)

EXPERIMENTAL

Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral temozolomide once daily on days 1-21.

Biological: Bevacizumab; Drug: Temozolomide

Arm II (bevacizumab & irinotecan hydrochloride)

EXPERIMENTAL

Patients receive bevacizumab IV as in Arm I followed by irinotecan hydrochloride IV over 90 minutes on days 1 and 15.

Biological: Bevacizumab; Drug: Irinotecan Hydrochloride

Interventions

Bevacizumab BIOLOGICAL

Given IV

Also known as: Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin, Bevacizumab Biosimilar BEVZ92, Bevacizumab Biosimilar BI 695502, Bevacizumab Biosimilar CBT 124, Bevacizumab Biosimilar FKB238, BEVACIZUMAB, LICENSE HOLDER UNSPECIFIED, Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer, Recombinant Humanized Anti-VEGF Monoclonal Antibody, rhuMab-VEGF

Arm I (bevacizumab and temozolomide); Arm II (bevacizumab & irinotecan hydrochloride)

Irinotecan Hydrochloride DRUG

Given IV

Also known as: Campto, Camptosar, Camptothecin 11, Camptothecin-11, CPT 11, CPT-11, Irinomedac, U-101440E

Arm II (bevacizumab & irinotecan hydrochloride)

Temozolomide DRUG

Given orally

Also known as: CCRG-81045, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831, M and B 39831, Methazolastone, RP-46161, SCH 52365, Temcad, Temodal, Temodar, Temomedac

Arm I (bevacizumab and temozolomide)

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed intracranial glioblastoma multiforme (GBM) or gliosarcoma
• Original histology of low-grade glioma with subsequent histological diagnosis of GBM or gliosarcoma allowed
• Recurrent or refractory disease, meeting all of the following criteria:
• Must have received prior temozolomide
• Pathologic or imaging confirmation of tumor progression or regrowth required
• Confirmation of true progressive disease (rather than radiation necrosis) by positron emission tomography, thallium scanning, MRI spectroscopy, or surgical documentation required for patients who received prior interstitial brachytherapy, Gliadel wafer, or stereotactic radiosurgery
• Unequivocal radiographic evidence of tumor progression by MRI within the past 14 days (while on a stable dose of steroids for ? 5 days)
• No acute intratumoral hemorrhage on MRI
• Patients with MRI demonstrating old hemorrhage or subacute blood after a neurosurgical procedure (biopsy or resection) are eligible
• Karnofsky performance status 70-100%
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for at least 6 months after completion of bevacizumab therapy
• Systolic blood pressure ? 160 mm Hg or diastolic blood pressure ? 90 mm Hg (antihypertensive medication allowed)
• Able to undergo brain MRI scans with intravenous gadolinium

Sponsors & Collaborators

• National Cancer Institute (NCI): lead
• American College of Radiology Imaging Network: collaborator
• Radiation Therapy Oncology Group: collaborator

Study Sites (93)

Mobile Infirmary Medical Center

Mobile, Alabama, 36607, United States

Location

Fairbanks Memorial Hospital

Fairbanks, Alaska, 99701, United States

Location

Arizona Oncology Services Foundation

Scottsdale, Arizona, 85260, United States

Location

Alta Bates Summit Medical Center-Herrick Campus

Berkeley, California, 94704, United States

Location

Mills-Peninsula Medical Center

Burlingame, California, 94010, United States

Location

John Muir Medical Center-Concord Campus

Concord, California, 94520, United States

Location

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

Marin General Hospital

Greenbrae, California, 94904, United States

Location

Sutter Cancer Research Consortium

Novato, California, 94945, United States

Location

California Pacific Medical Center-Pacific Campus

San Francisco, California, 94115, United States

Location

Sutter Solano Medical Center/Cancer Center

Vallejo, California, 94589, United States

Location

John Muir Medical Center-Walnut Creek

Walnut Creek, California, 94598, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

Boca Raton Regional Hospital

Boca Raton, Florida, 33486, United States

Location

University of Florida Health Science Center - Gainesville

Gainesville, Florida, 32610, United States

Location

Saint Luke's Mountain States Tumor Institute

Boise, Idaho, 83712, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

Saint Vincent Anderson Regional Hospital/Cancer Center

Anderson, Indiana, 46016, United States

Location

Franciscan Saint Francis Health-Beech Grove

Beech Grove, Indiana, 46107, United States

Location

IU Health Methodist Hospital

Indianapolis, Indiana, 46202, United States

Location

Reid Health

Richmond, Indiana, 47374, United States

Location

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

Location

Anne Arundel Medical Center

Annapolis, Maryland, 21401, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Borgess Medical Center

Kalamazoo, Michigan, 49001, United States

Location

Bronson Methodist Hospital

Kalamazoo, Michigan, 49007, United States

Location

West Michigan Cancer Center

Kalamazoo, Michigan, 49007, United States

Location

William Beaumont Hospital-Royal Oak

Royal Oak, Michigan, 48073, United States

Location

Fairview Ridges Hospital

Burnsville, Minnesota, 55337, United States

Location

Mercy Hospital

Coon Rapids, Minnesota, 55433, United States

Location

Fairview-Southdale Hospital

Edina, Minnesota, 55435, United States

Location

Unity Hospital

Fridley, Minnesota, 55432, United States

Location

Minnesota Oncology Hematology PA-Maplewood

Maplewood, Minnesota, 55109, United States

Location

Abbott-Northwestern Hospital

Minneapolis, Minnesota, 55407, United States

Location

North Memorial Medical Health Center

Robbinsdale, Minnesota, 55422, United States

Location

Park Nicollet Clinic - Saint Louis Park

Saint Louis Park, Minnesota, 55416, United States

Location

United Hospital

Saint Paul, Minnesota, 55102, United States

Location

Ridgeview Medical Center

Waconia, Minnesota, 55387, United States

Location

Minnesota Oncology Hematology PA-Woodbury

Woodbury, Minnesota, 55125, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Northern Rockies Radiation Oncology Center

Billings, Montana, 59101, United States

Location

Cheshire Medical Center-Dartmouth-Hitchcock Keene

Keene, New Hampshire, 03431, United States

Location

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

John F Kennedy Medical Center

Edison, New Jersey, 08818, United States

Location

New Mexico Oncology Hematology Consultants

Albuquerque, New Mexico, 87109, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Highland Hospital

Rochester, New York, 14620, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Mission Hospital-Memorial Campus

Asheville, North Carolina, 28801, United States

Location

Carolinas Medical Center/Levine Cancer Institute

Charlotte, North Carolina, 28203, United States

Location

Akron General Medical Center

Akron, Ohio, 44307, United States

Location

Grandview Hospital

Dayton, Ohio, 45405, United States

Location

Good Samaritan Hospital - Dayton

Dayton, Ohio, 45406, United States

Location

Miami Valley Hospital

Dayton, Ohio, 45409, United States

Location

Samaritan North Health Center

Dayton, Ohio, 45415, United States

Location

Dayton NCI Community Oncology Research Program

Dayton, Ohio, 45420, United States

Location

Veteran Affairs Medical Center

Dayton, Ohio, 45428, United States

Location

Blanchard Valley Hospital

Findlay, Ohio, 45840, United States

Location

Atrium Medical Center-Middletown Regional Hospital

Franklin, Ohio, 45005-1066, United States

Location

Kettering Medical Center

Kettering, Ohio, 45429, United States

Location

Upper Valley Medical Center

Troy, Ohio, 45373, United States

Location

Greene Memorial Hospital

Xenia, Ohio, 45385, United States

Location

Legacy Mount Hood Medical Center

Gresham, Oregon, 97030, United States

Location

Providence Milwaukie Hospital

Milwaukie, Oregon, 97222, United States

Location

Legacy Good Samaritan Hospital and Medical Center

Portland, Oregon, 97210, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

Adventist Medical Center

Portland, Oregon, 97216, United States

Location

Providence Saint Vincent Medical Center

Portland, Oregon, 97225, United States

Location

Legacy Emanuel Hospital and Health Center

Portland, Oregon, 97227, United States

Location

Legacy Meridian Park Hospital

Tualatin, Oregon, 97062, United States

Location

Radiation Therapy Oncology Group

Philadelphia, Pennsylvania, 19103, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

American Fork Hospital / Huntsman Intermountain Cancer Center

American Fork, Utah, 84003, United States

Location

Sandra L Maxwell Cancer Center

Cedar City, Utah, 84720, United States

Location

Cottonwood Hospital Medical Center

Murray, Utah, 84107, United States

Location

Intermountain Medical Center

Murray, Utah, 84107, United States

Location

McKay-Dee Hospital Center

Ogden, Utah, 84403, United States

Location

Utah Valley Regional Medical Center

Provo, Utah, 84604, United States

Location

Intermountain Health Care

Salt Lake City, Utah, 84103, United States

Location

Utah Cancer Specialists-Salt Lake City

Salt Lake City, Utah, 84106, United States

Location

LDS Hospital

Salt Lake City, Utah, 84143, United States

Location

Dixie Medical Center Regional Cancer Center

St. George, Utah, 84770, United States

Location

Norris Cotton Cancer Center-North

Saint Johnsbury, Vermont, 05819, United States

Location

Saint Francis Hospital

Federal Way, Washington, 98003, United States

Location

EvergreenHealth Medical Center

Kirkland, Washington, 98033, United States

Location

Virginia Mason Medical Center

Seattle, Washington, 98101, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

PeaceHealth Southwest Medical Center

Vancouver, Washington, 98664, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

Froedtert and the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma; Brain Neoplasms

Interventions

Bevacizumab; Immunoglobulin G; Disulfides; Irinotecan; Temozolomide

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; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immunoglobulin Isotypes; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals; Camptothecin; Alkaloids; Heterocyclic Compounds; Dacarbazine; Triazenes; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Wendy Seiferheld
• Organization: NRG Oncology

seiferheldw@nrgoncology.org

Study Officials

• Mark Gilbert

  Radiation Therapy Oncology Group

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2007
• First Posted: February 12, 2007
• Study Start: March 1, 2007
• Primary Completion: January 21, 2010
• Study Completion: February 16, 2011
• Last Updated: September 17, 2018
• Results First Posted: May 1, 2013

Record last verified: 2018-08

Locations

US (93)