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

A Randomized Phase II Trial of Bevacizumab With Irinotecan or Bevacizumab With Temozolomide in Recurrent Glioblastoma

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.

Study Overview

• Status: Completed
• Conditions: Adult Glioblastoma; Adult Gliosarcoma; Recurrent Adult Brain Neoplasm
• Intervention / Treatment: Biological: Bevacizumab; Drug: Irinotecan Hydrochloride; Drug: Temozolomide

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the efficacy of bevacizumab and irinotecan hydrochloride, in terms of 6-month progression-free survival rate, in patients with recurrent or refractory intracranial glioblastoma multiforme or gliosarcoma.

II. Determine the adverse event profile and tolerability of bevacizumab and temozolomide in these patients.

SECONDARY OBJECTIVES:

I. Determine the efficacy of bevacizumab and temozolomide, in terms of 6-month progression-free survival rate, in patients previously treated with temozolomide.

II. Determine the efficacy of bevacizumab and irinotecan hydrochloride, in terms of objective response, in patients with measurable disease.

III. Determine the efficacy of bevacizumab and temozolomide, in terms of objective response, in patients with measurable disease who were previously treated with temozolomide.

IV. Determine the toxicity profile and tolerability of bevacizumab and irinotecan hydrochloride in these patients.

TERTIARY OBJECTIVES:

I. Assess the potential role of perfusion MRI and magnetic resonance spectroscopy imaging as an early indicator of response to therapy after 2 weeks of treatment with bevacizumab.

II. Assess the potential role of perfusion MRI and magnetic resonance spectroscopy imaging as a prognostic indicator based on images taken at baseline, at 2 weeks, and after 2 courses of study treatment.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age (< 50 vs >= 50 years of age) and Karnofsky performance status (70-80% vs 90-100%). Patients are randomized to 1 of 2 treatment arms with a 2:1 ratio (arm I:arm II).

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

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

In both arms, treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. All patients undergo MRI at baseline and at every 2 courses (no 2-week MRI) per standard of care until progression or discontinuation of treatment to assess areas of breakdown of the blood-brain barrier. Patients undergo an additional MRI after study therapy. Consenting patients also undergo diffusion and perfusion MRI and magnetic resonance spectroscopic imaging for correlative studies.

After completion of study therapy, patients are followed up for at least 1 month.

• Study Type: Interventional
• Enrollment (Actual): 123
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Mobile, Alabama, United States, 36607
      • Mobile Infirmary Medical Center
  • Alaska
    • Fairbanks, Alaska, United States, 99701
      • Fairbanks Memorial Hospital
  • Arizona
    • Scottsdale, Arizona, United States, 85260
      • Arizona Oncology Services Foundation
  • California
    • Berkeley, California, United States, 94704
      • Alta Bates Summit Medical Center-Herrick Campus
    • Burlingame, California, United States, 94010
      • Mills-Peninsula Medical Center
    • Concord, California, United States, 94520
      • John Muir Medical Center-Concord Campus
    • Duarte, California, United States, 91010
      • City of Hope Comprehensive Cancer Center
    • Greenbrae, California, United States, 94904
      • Marin General Hospital
    • Novato, California, United States, 94945
      • Sutter Cancer Research Consortium
    • San Francisco, California, United States, 94115
      • California Pacific Medical Center-Pacific Campus
    • Vallejo, California, United States, 94589
      • Sutter Solano Medical Center/Cancer Center
    • Walnut Creek, California, United States, 94598
      • John Muir Medical Center-Walnut Creek
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Boca Raton Regional Hospital
    • Gainesville, Florida, United States, 32610
      • University of Florida Health Science Center - Gainesville
  • Idaho
    • Boise, Idaho, United States, 83712
      • Saint Luke's Mountain States Tumor Institute
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Comprehensive Cancer Center
  • Indiana
    • Anderson, Indiana, United States, 46016
      • Saint Vincent Anderson Regional Hospital/Cancer Center
    • Beech Grove, Indiana, United States, 46107
      • Franciscan Saint Francis Health-Beech Grove
    • Indianapolis, Indiana, United States, 46202
      • IU Health Methodist Hospital
    • Richmond, Indiana, United States, 47374
      • Reid Health
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa/Holden Comprehensive Cancer Center
  • Maryland
    • Annapolis, Maryland, United States, 21401
      • Anne Arundel Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Comprehensive Cancer Center
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Kalamazoo, Michigan, United States, 49007
      • West Michigan Cancer Center
    • Kalamazoo, Michigan, United States, 49007
      • Bronson Methodist Hospital
    • Kalamazoo, Michigan, United States, 49001
      • Borgess Medical Center
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital-Royal Oak
  • Minnesota
    • Burnsville, Minnesota, United States, 55337
      • Fairview Ridges Hospital
    • Coon Rapids, Minnesota, United States, 55433
      • Mercy Hospital
    • Edina, Minnesota, United States, 55435
      • Fairview-Southdale Hospital
    • Fridley, Minnesota, United States, 55432
      • Unity Hospital
    • Maplewood, Minnesota, United States, 55109
      • Minnesota Oncology Hematology PA-Maplewood
    • Minneapolis, Minnesota, United States, 55407
      • Abbott-Northwestern Hospital
    • Robbinsdale, Minnesota, United States, 55422
      • North Memorial Medical Health Center
    • Saint Louis Park, Minnesota, United States, 55416
      • Park Nicollet Clinic - Saint Louis Park
    • Saint Paul, Minnesota, United States, 55102
      • United Hospital
    • Waconia, Minnesota, United States, 55387
      • Ridgeview Medical Center
    • Woodbury, Minnesota, United States, 55125
      • Minnesota Oncology Hematology PA-Woodbury
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Montana
    • Billings, Montana, United States, 59101
      • Northern Rockies Radiation Oncology Center
  • New Hampshire
    • Keene, New Hampshire, United States, 03431
      • Cheshire Medical Center-Dartmouth-Hitchcock Keene
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • New Jersey
    • Edison, New Jersey, United States, 08818
      • John F Kennedy Medical Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • New Mexico Oncology Hematology Consultants
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center
    • Rochester, New York, United States, 14642
      • University of Rochester
    • Rochester, New York, United States, 14620
      • Highland Hospital
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mission Hospital-Memorial Campus
    • Charlotte, North Carolina, United States, 28203
      • Carolinas Medical Center/Levine Cancer Institute
  • Ohio
    • Akron, Ohio, United States, 44307
      • Akron General Medical Center
    • Dayton, Ohio, United States, 45406
      • Good Samaritan Hospital - Dayton
    • Dayton, Ohio, United States, 45409
      • Miami Valley Hospital
    • Dayton, Ohio, United States, 45415
      • Samaritan North Health Center
    • Dayton, Ohio, United States, 45420
      • Dayton NCI Community Oncology Research Program
    • Dayton, Ohio, United States, 45405
      • Grandview Hospital
    • Dayton, Ohio, United States, 45428
      • Veteran Affairs Medical Center
    • Findlay, Ohio, United States, 45840
      • Blanchard Valley Hospital
    • Franklin, Ohio, United States, 45005-1066
      • Atrium Medical Center-Middletown Regional Hospital
    • Kettering, Ohio, United States, 45429
      • Kettering Medical Center
    • Troy, Ohio, United States, 45373
      • Upper Valley Medical Center
    • Xenia, Ohio, United States, 45385
      • Greene Memorial Hospital
  • Oregon
    • Gresham, Oregon, United States, 97030
      • Legacy Mount Hood Medical Center
    • Milwaukie, Oregon, United States, 97222
      • Providence Milwaukie Hospital
    • Portland, Oregon, United States, 97210
      • Legacy Good Samaritan Hospital and Medical Center
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
    • Portland, Oregon, United States, 97225
      • Providence Saint Vincent Medical Center
    • Portland, Oregon, United States, 97227
      • Legacy Emanuel Hospital and Health Center
    • Portland, Oregon, United States, 97216
      • Adventist Medical Center
    • Tualatin, Oregon, United States, 97062
      • Legacy Meridian Park Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
    • Philadelphia, Pennsylvania, United States, 19103
      • Radiation Therapy Oncology Group
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center
  • Utah
    • American Fork, Utah, United States, 84003
      • American Fork Hospital / Huntsman Intermountain Cancer Center
    • Cedar City, Utah, United States, 84720
      • Sandra L Maxwell Cancer Center
    • Murray, Utah, United States, 84107
      • Intermountain Medical Center
    • Murray, Utah, United States, 84107
      • Cottonwood Hospital Medical Center
    • Ogden, Utah, United States, 84403
      • McKay-Dee Hospital Center
    • Provo, Utah, United States, 84604
      • Utah Valley Regional Medical Center
    • Saint George, Utah, United States, 84770
      • Dixie Medical Center Regional Cancer Center
    • Salt Lake City, Utah, United States, 84106
      • Utah Cancer Specialists-Salt Lake City
    • Salt Lake City, Utah, United States, 84143
      • LDS Hospital
    • Salt Lake City, Utah, United States, 84103
      • Intermountain Health Care
  • Vermont
    • Saint Johnsbury, Vermont, United States, 05819
      • Norris Cotton Cancer Center-North
  • Washington
    • Federal Way, Washington, United States, 98003
      • Saint Francis Hospital
    • Kirkland, Washington, United States, 98033
      • EvergreenHealth Medical Center
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center
    • Vancouver, Washington, United States, 98664
      • PeaceHealth Southwest Medical Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospital and Clinics
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert and The Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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
• Absolute neutrophil count ? 1,500 cells/mm?
• Platelet count ? 100,000 cells/mm?
• Hemoglobin ? 10 g/dL (transfusion or other intervention allowed)
• WBC ? 3,000 cells/mm?
• AST < 2 times upper limit of normal
• Bilirubin ? 1.6 mg/dL
• Creatinine < 1.5 mg/dL
• Urine protein:creatinine ratio ? 0.5 by urinalysis OR total urinary protein < 1,000 mg by 24-hour urine collection
• INR < 1.4 (for patients not on warfarin)
• No patients with severely impaired renal function (i.e., estimated glomerular filtration rate < 30 mL/min or on dialysis)
• No other prior invasive malignancy, except nonmelanomatous skin cancer or carcinoma in situ of the cervix, unless the patient has been disease free and off therapy for that disease for ? 3 years

• No severe, active comorbidity, defined as any of the following:

  • Transmural myocardial infarction or unstable angina within the past 6 months
  • Evidence of recent myocardial infarction or ischemia manifested as ST elevation of ? 2 mm by EKG performed within the past 14 days
  • New York Heart Association class II-IV congestive heart failure requiring hospitalization within the past 12 months
  • History of stroke or transient ischemic attack within the past 6 months
  • Cerebrovascular accident within the past 6 months
  • Serious and inadequately controlled cardiac arrhythmia
  • Significant vascular disease (e.g., aortic aneurysm or history of aortic dissection)
  • Clinically significant peripheral vascular disease
  • Evidence of bleeding diathesis or coagulopathy
  • Serious or nonhealing wound, ulcer, or bone fracture
  • Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
  • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of study entry
  • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within the past 14 days
  • Acquired immune deficiency syndrome (AIDS)
• No significant traumatic injury within the past 28 days
• No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
• No condition that impairs the ability to swallow pills (e.g., gastrointestinal tract disease resulting in an inability to take oral medication; requirement for IV alimentation; prior surgical procedures affecting absorption; or active peptic ulcer disease)
• No disease that would obscure toxicity or dangerously alter drug metabolism
• No concurrent major surgical procedures
• Recovered from prior therapy

• Recent resection of recurrent or progressive tumor allowed provided the following criteria are met:

  • Failed prior radiotherapy that was completed ? 42 days ago
  • Residual disease after resection of recurrent glioblastoma is not mandated
• More than 28 days since prior surgery or open biopsy
• More than 7 days since prior core or needle biopsy
• At least 28 days since prior investigational agents
• At least 14 days since prior vincristine
• At least 42 days since prior nitrosoureas
• At least 21 days since prior procarbazine
• At least 28 days since other prior cytotoxic therapy
• At least 7 days since prior noncytotoxic agents (e.g., interferon, tamoxifen, thalidomide, or isotretinoin [except radiosensitizers])

• At least 14 days since prior enzyme-inducing antiepileptic drugs (EIAEDs)

  • Concurrent non-hepatic EIAEDs allowed
• No other concurrent CYP3A4 inducers, such as rifampin or Hypericum perforatum (St. John's wort)

• Concurrent full-dose anticoagulants (e.g., warfarin or low molecular weight heparin) allowed provided all of the following criteria are met:

  • No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)
  • In-range INR (usually between 2 and 3) on a stable dose of oral anticoagulants or on a stable dose of low molecular weight heparin
• No concurrent highly active antiretroviral therapy
• No concurrent prophylactic use of growth factors

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (bevacizumab and temozolomide); Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral temozolomide once daily on days 1-21.	Biological: Bevacizumab; Given IV; Other Names: Avastin; Anti-VEGF; Anti-VEGF Humanized Monoclonal Antibody; Anti-VEGF rhuMAb; Bevacizumab Biosimilar BEVZ92; Bevacizumab Biosimilar BI 695502; Bevacizumab Biosimilar CBT 124; Bevacizumab Biosimilar FKB238; 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; BEVACIZUMAB, LICENSE HOLDER UNSPECIFIED; Drug: Temozolomide; Given orally; Other Names: Temodar; SCH 52365; Temodal; Temcad; Methazolastone; RP-46161; Temomedac; 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
Experimental: Arm II (bevacizumab & irinotecan hydrochloride); Patients receive bevacizumab IV as in Arm I followed by irinotecan hydrochloride IV over 90 minutes on days 1 and 15.	Biological: Bevacizumab; Given IV; Other Names: Avastin; Anti-VEGF; Anti-VEGF Humanized Monoclonal Antibody; Anti-VEGF rhuMAb; Bevacizumab Biosimilar BEVZ92; Bevacizumab Biosimilar BI 695502; Bevacizumab Biosimilar CBT 124; Bevacizumab Biosimilar FKB238; 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; BEVACIZUMAB, LICENSE HOLDER UNSPECIFIED; Drug: Irinotecan Hydrochloride; Given IV; Other Names: Campto; Camptosar; U-101440E; CPT-11; Camptothecin 11; Camptothecin-11; CPT 11; Irinomedac

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Count/Percentage of Patients Progression-free at 6 Months for Bevacizumab and Temozolomide 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.
Patients' Best Objective Response (Complete Response, Partial Response, Stable Disease, Progression)	Tumor size measured in millimeters and is the largest crosssectional area using perpendicular measurements of contrast enhancing abnormality. Complete response (CR): Complete disappearance of all enhancing tumor on consecutive MRI scans at least 1 month apart, off corticosteroids, and neurologically stable or improved. Partial response (PR): ≥ 50% decrease in size of enhancing tumor on consecutive MRI scans at least 1 month apart, corticosteroids stable or reduced, and neurologically stable or improved. Progressive disease (PD): ≥ 25% increase in the size of enhancing tumor or any new tumor; or neurologically worse, and steroids stable or increased. Stable disease (SD): Does not qualify for CR, PR, or PD.	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	Local and central interpretations of the standard MRI were assessed for progression and survival at all available imaging (baseline visit, week 2, and after every 2 cycles of treatment, and at termination of treatment). Patients who suffer clinical progression without radiographic confirmation of progression were considered to have progressive disease in determination of PFS-6. Subjects participated in the MR substudies regardless of therapeutic intervention	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	Local reads were treated as the test and central reads were treated as the reference standard. Thus, a participant meeting the definition of progression on any standard MRI central interpretation (baseline visit, week 2, after every 2 cycles of treatment, and at termination of treatment) was considered positive for PFS-6. Therefore, a true positive is defined as a positive local interpretation for a subject with a positive central read.	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	Aim not included in final (February 10, 2009) protocol (removed from section 2).	2 weeks following initiation of protocol treatment (T1) and at 8 weeks following chemotherapy with bevacizumab (T2)
Correlation of Degree of Cerebral Blood Volume (CBV) and Lactate (Lac) to Patient Response	Aim not included in final (February 10, 2009) protocol (removed from section 2)	2 weeks following initiation of protocol treatment (T1)
Predictive Value of CBV and Lac/NAA in Assessing 6-month Progression-free Survival	Aim not included in final (February 10, 2009) protocol (removed from section 2)	2 weeks following initiation of protocol treatment (T1)
Change in Perfusion MRI Markers at Week 2 as Predictors of 12mo Overall Survival (OS)	To assess the potential role of perfusion MRI as a prognostic indicator for 12-month OS based on the change in MRI markers evaluated before treatment and 2 weeks following initiation of protocol treatment. Percent change in mean tumor relative cerebral blood volume (rCBV) derived from dynamic susceptibility contrast (DSC) MRI normalized to white matter (nRCBV) and standardized rCBV (sRCBV) between baseline and week 2 are the prognostic indicators.	Baseline and 2 Weeks
Change in Perfusion MRI Markers at Week 8 as Predictors of 12mo Overall Survival (OS)	To assess the potential role of perfusion MRI as a prognostic indicator for 12-month OS based on the change in MRI markers evaluated before treatment and 8 weeks following initiation of protocol treatment. Percent change in mean tumor relative cerebral blood volume (rCBV) derived from dynamic susceptibility contrast (DSC) MRI normalized to white matter (nRCBV) and standardized rCBV (sRCBV) between baseline and week 8 are the prognostic indicators.	Baseline and 8 weeks
Change in Perfusion MRI Markers at Week 16 as Predictors of 12mo Overall Survival (OS)	To assess the potential role of perfusion MRI as a prognostic indicator for 12-month OS based on the change in MRI markers evaluated before treatment and 16 weeks following initiation of protocol treatment. Percent change in mean tumor relative cerebral blood volume (rCBV) derived from dynamic susceptibility contrast (DSC) MRI normalized to white matter (nRCBV) and standardized rCBV (sRCBV) between baseline and week 16 are the prognostic indicators.	Baseline and 16 Weeks

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Collaborators: Radiation Therapy Oncology Group; American College of Radiology Imaging Network
• Investigators: Principal Investigator: Mark Gilbert, Radiation Therapy Oncology Group

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2007
• Primary Completion (Actual): January 21, 2010
• Study Completion (Actual): February 16, 2011

Study Registration Dates

• First Submitted: February 8, 2007
• First Submitted That Met QC Criteria: February 8, 2007
• First Posted (Estimate): February 12, 2007

Study Record Updates

• Last Update Posted (Actual): September 17, 2018
• Last Update Submitted That Met QC Criteria: August 17, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Disease Attributes; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Glioblastoma; Recurrence; Brain Neoplasms; Gliosarcoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Phytogenic; Topoisomerase Inhibitors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Topoisomerase I Inhibitors; Antibodies; Temozolomide; Immunoglobulins; Bevacizumab; Irinotecan; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Immunoglobulin G; Endothelial Growth Factors; Camptothecin
• Other Study ID Numbers: NCI-2009-00743 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA021661 (U.S. NIH Grant/Contract); RTOG-0625 (Other Identifier: CTEP); ACRIN-6677 (Other Identifier: ACRIN); CDR0000528259 (Registry Identifier: CDR); RTOG 0625 (Other Identifier: Radiation Therapy Oncology Group)