Temozolomide and Radiation Therapy With or Without Cediranib Maleate in Treating Patients With Newly Diagnosed Glioblastoma

NCT ID: NCT01062425

Last Updated: 2022-07-26

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

261 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-02-26

Study Completion Date

2022-05-20

Brief Summary

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This randomized phase II trial studies temozolomide, radiation therapy, and cediranib maleate to see how well they work compared with temozolomide, radiation therapy, and a placebo in treating patients with newly diagnosed glioblastoma (a type of brain tumor). Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high energy x-rays to kill tumor cells. Cediranib maleate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. It is not yet known whether temozolomide and radiation therapy are more effective when given with or without cediranib maleate in treating glioblastoma.

Detailed Description

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PRIMARY OBJECTIVES:

I. To determine if the addition of cediranib (cediranib maleate) to chemoradiation treatment enhances treatment efficacy as measured by the 6-month progression-free survival rate.

SECONDARY OBJECTIVES:

I. To determine if the addition of cediranib to chemoradiation treatment enhances treatment efficacy as measured by overall survival.

II. To determine if the addition of cediranib to chemoradiation treatment enhances treatment efficacy as measured by progression-free survival.

III. To determine if there is an association between tumor O6-methylguanine-deoxyribonucleic acid (DNA) methyltransferase (MGMT) gene methylation status and treatment response and outcome.

IV. To compare and record the toxicities of the cediranib + chemoradiation arm versus the chemoradiation arm.

V. To evaluate whether 6-month progression-free survival is associated with overall survival.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive cediranib maleate orally (PO) once daily (QD) for 3 days. Patients then undergo radiation therapy (intensity-modulated radiation therapy or 3-dimensional conformal radiation therapy) QD, 5 days a week, for 6 weeks and receive temozolomide PO QD and cediranib maleate PO QD for 6 weeks. Patients then receive temozolomide PO QD alone on days 1-5. Treatment with temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive placebo PO QD for 3 days. Patients then undergo radiation therapy (intensity-modulated radiation therapy or 3-dimensional conformal radiation therapy) QD, 5 days a week, for 6 weeks and receive temozolomide PO QD and placebo PO QD for 6 weeks. Patients then receive temozolomide PO QD alone on days 1-5. Treatment with temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for 1 year, and then every 6 months thereafter.

Conditions

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Adult Glioblastoma Adult Gliosarcoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Cediranib, TMZ, and RT

Cediranib (3 days) followed by radiation therapy (RT) + daily temozolomide (TMZ) + cediranib followed by cediranib monotherapy (4 weeks) followed by TMZ + cediranib for 12 cycle maximum.

Group Type EXPERIMENTAL

3-Dimensional Conformal Radiation Therapy

Intervention Type RADIATION

Undergo 3-dimensional conformal radiotherapy

Cediranib Maleate

Intervention Type DRUG

Given PO

Intensity-Modulated Radiation Therapy

Intervention Type RADIATION

Undergo intensity-modulated radiation therapy

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Temozolomide

Intervention Type DRUG

Given PO

Placebo, TMZ, and RT

Placebo (3 days) followed by radiation therapy (RT) + daily temozolomide (TMZ) + placebo followed by placebo monotherapy (4 weeks) followed by TMZ + placebo for 12 cycle maximum.

Group Type ACTIVE_COMPARATOR

3-Dimensional Conformal Radiation Therapy

Intervention Type RADIATION

Undergo 3-dimensional conformal radiotherapy

Intensity-Modulated Radiation Therapy

Intervention Type RADIATION

Undergo intensity-modulated radiation therapy

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Placebo Administration

Intervention Type OTHER

Given PO

Temozolomide

Intervention Type DRUG

Given PO

Interventions

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3-Dimensional Conformal Radiation Therapy

Undergo 3-dimensional conformal radiotherapy

Intervention Type RADIATION

Cediranib Maleate

Given PO

Intervention Type DRUG

Intensity-Modulated Radiation Therapy

Undergo intensity-modulated radiation therapy

Intervention Type RADIATION

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Placebo Administration

Given PO

Intervention Type OTHER

Temozolomide

Given PO

Intervention Type DRUG

Other Intervention Names

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3-dimensional radiation therapy 3D Conformal 3D CONFORMAL RADIATION THERAPY 3D CRT 3D-CRT Conformal Therapy Radiation Conformal Therapy Radiation, 3D Conformal AZD2171 AZD2171 Maleate Recentin IMRT Intensity Modulated RT Intensity-Modulated Radiotherapy Radiation, Intensity-Modulated Radiotherapy 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 TMZ

Eligibility Criteria

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Inclusion Criteria

* Histologically proven diagnosis of glioblastoma or gliosarcoma (World Health Organization \[WHO\] grade IV) confirmed by central review prior to step 2 registration
* Tumor tissue that is determined by central pathology review prior to step 2 registration to be of sufficient size for analysis of MGMT status

* Patients must have at least 1 block of tumor tissue; submission of 2 blocks is strongly encouraged
* Cavitron ultrasonic aspirator (CUSA)-derived material is not allowed; fresh frozen tumor tissue acquisition is encouraged
* Diagnosis must be made by surgical excision, either partial or complete; stereotactic biopsy is not allowed because it will not provide sufficient tissue for MGMT analysis
* The tumor tissue must be sent as soon as possible to maximize the likelihood of eligibility; tumor tissue may not be submitted later than 28 days after the surgical procedure, because tissue analysis will not be able to be performed in time for treatment to commence by the mandatory 6-week post-surgery outer limit; submission of tissue earlier than 28 days post-surgery is highly recommended
* The tumor must have a supratentorial component
* History/physical examination, including neurologic examination, within 14 days prior to step 2 registration
* The patient must have recovered from the effects of surgery, post-operative infection, and other complications before step 2 registration
* A diagnostic contrast-enhanced magnetic resonance imaging (MRI) of the brain must be performed preoperatively and postoperatively prior to step 1 registration; the postoperative scan must be performed within 28 days prior to step 1 registration
* Documentation of steroid doses/concurrent medications within 14 days prior to step 2 registration
* Karnofsky performance status \>= 70 within 14 days prior to step 2 registration
* Complete blood count (CBC)/differential obtained within 14 days prior to step 2 registration on study, with adequate bone marrow function defined as follows:
* Absolute neutrophil count (ANC) \>= 1,800 cells/mm\^3
* Platelets \>= 100,000 cells/mm\^3
* Hemoglobin \>=10.0 g/dl (Note: The use of transfusion or other intervention to achieve hemoglobin (Hgb) \>= 10.0 g/dl is acceptable)
* Adequate renal function, as defined below:
* Blood urea nitrogen (BUN) =\< 30 mg/dl within 14 days prior to step 2 registration
* Creatinine =\< 1.7 mg/dl within 14 days prior to step 2 registration
* Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =\< 3 x normal range within 14 days prior to step 2 registration
* Systolic blood pressure =\< 140 mm Hg AND diastolic pressure =\< 90 mm Hg within 14 days prior to step 2 registration in the presence or absence of a stable regimen of anti-hypertensive therapy
* Prothrombin time/international normalized ratio (PT INR) \< 1.4 for patients not on warfarin confirmed by testing within 1 week of step 2 registration
* Patients on full-dose anticoagulants (e.g., warfarin or low molecular weight \[LMW\] heparin) must meet both of the following criteria:

* 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 anticoagulant or on a stable dose of low molecular weight heparin
* Patient must provide study specific informed consent prior to step 1 registration
* Women of childbearing potential and male participants must practice adequate contraception
* For females of child-bearing potential, negative serum pregnancy test within 14 days prior to step 2 registration

Exclusion Criteria

* Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease free for \>= 3 years; (for example, carcinoma in situ of the breast, oral cavity, and cervix are all permissible)
* Recurrent or multifocal malignant gliomas
* Metastases detected below the tentorium or beyond the cranial vault
* Prior chemotherapy or radiosensitizers for cancers of the head and neck region; note that prior chemotherapy for a different cancer is allowable (except temozolomide or cediranib); prior use of Gliadel wafers or any other intratumoral or intracavitary treatment are not permitted
* Prior radiotherapy to the head or neck (except for T1 glottic cancer), resulting in overlap of radiation fields
* Severe, active co-morbidity, defined as follows:

* Unstable angina and/or congestive heart failure requiring hospitalization
* Transmural myocardial infarction within the last 6 months
* Evidence of recent myocardial infarction or ischemia by the findings of S-T elevations of \>= 2 mm using the analysis of an electrocardiogram (EKG) performed within 14 days of step 2 registration
* New York Heart Association grade II or greater congestive heart failure requiring hospitalization within 12 months prior to step 2 registration
* History of stroke, cerebral vascular accident (CVA) or transient ischemic attack within 6 months
* Serious and inadequately controlled cardiac arrhythmia
* Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection) or clinically significant peripheral vascular disease
* Evidence of bleeding diathesis or coagulopathy
* Serious or non-healing wound, ulcer, or bone fracture or history of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to step 2 registration, with the exception of the craniotomy for tumor resection
* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of step 2 registration
* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of step 2 registration
* Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
* Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol
* Active connective tissue disorders, such as lupus or scleroderma, which in the opinion of the treating physician may put the patient at high risk for radiation toxicity
* Any other major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy
* Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception
* Pregnant or lactating women
* Prior allergic reaction to temozolomide
* Patients treated on any other therapeutic clinical protocols within 30 days prior to step 1 registration or during participation in the study
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to cediranib
* Mean QTc \>500 msec (with Bazett's correction) in screening electrocardiogram or history of familial long QT syndrome or other significant ECG abnormality noted within 14 days of treatment
* Patients receiving concurrent vascular endothelial growth factor (VEGF) inhibitors are prohibited from participating in this study
* Patients must not be on enzyme-inducing anti-epileptic drugs (EIAED); patients may be on non-enzyme inducing anti-epileptic drugs (NEIAED) or may not be taking any anti-epileptic drugs; in patients who have previously been on EIAED there must be at least a 14 day period since the last dose of an EIAED before the first dose of cediranib
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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NRG Oncology

OTHER

Sponsor Role collaborator

Radiation Therapy Oncology Group

NETWORK

Sponsor Role collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Tracy T Batchelor

Role: PRINCIPAL_INVESTIGATOR

NRG Oncology

Locations

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University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, United States

Site Status

The Kirklin Clinic at Acton Road

Birmingham, Alabama, United States

Site Status

Arizona Oncology Services Foundation

Scottsdale, Arizona, United States

Site Status

Banner University Medical Center - Tucson

Tucson, Arizona, United States

Site Status

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Site Status

Saint Joseph Hospital - Orange

Orange, California, United States

Site Status

Poudre Valley Hospital

Fort Collins, Colorado, United States

Site Status

Smilow Cancer Hospital Care Center at Saint Francis

Hartford, Connecticut, United States

Site Status

The Hospital of Central Connecticut

New Britain, Connecticut, United States

Site Status

Yale University

New Haven, Connecticut, United States

Site Status

Christiana Care Health System-Christiana Hospital

Newark, Delaware, United States

Site Status

AdventHealth Orlando

Orlando, Florida, United States

Site Status

Bay Medical Center

Panama City, Florida, United States

Site Status

Emory University Hospital Midtown

Atlanta, Georgia, United States

Site Status

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, United States

Site Status

Queen's Medical Center

Honolulu, Hawaii, United States

Site Status

University of Hawaii Cancer Center

Honolulu, Hawaii, United States

Site Status

The Cancer Center of Hawaii-Liliha

Honolulu, Hawaii, United States

Site Status

Saint Alphonsus Cancer Care Center-Boise

Boise, Idaho, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

OSF Saint Francis Medical Center

Peoria, Illinois, United States

Site Status

Carle Cancer Center

Urbana, Illinois, United States

Site Status

Radiation Oncology Associates PC

Fort Wayne, Indiana, United States

Site Status

Parkview Hospital Randallia

Fort Wayne, Indiana, United States

Site Status

IU Health Methodist Hospital

Indianapolis, Indiana, United States

Site Status

University of Kansas Cancer Center

Kansas City, Kansas, United States

Site Status

Kansas City NCI Community Oncology Research Program

Prairie Village, Kansas, United States

Site Status

Baptist Health Lexington

Lexington, Kentucky, United States

Site Status

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, United States

Site Status

Maine Medical Center- Scarborough Campus

Scarborough, Maine, United States

Site Status

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Site Status

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Saint Joseph Mercy Hospital

Ann Arbor, Michigan, United States

Site Status

Henry Ford Macomb Hospital-Clinton Township

Clinton Township, Michigan, United States

Site Status

Henry Ford Hospital

Detroit, Michigan, United States

Site Status

Ascension Saint John Hospital

Detroit, Michigan, United States

Site Status

Genesys Regional Medical Center-West Flint Campus

Flint, Michigan, United States

Site Status

West Michigan Cancer Center

Kalamazoo, Michigan, United States

Site Status

Sparrow Hospital

Lansing, Michigan, United States

Site Status

Saint Joseph Mercy Oakland

Pontiac, Michigan, United States

Site Status

Lake Huron Medical Center

Port Huron, Michigan, United States

Site Status

Ascension Saint Mary's Hospital

Saginaw, Michigan, United States

Site Status

Saint John Macomb-Oakland Hospital

Warren, Michigan, United States

Site Status

Mercy Hospital

Coon Rapids, Minnesota, United States

Site Status

Minnesota Oncology Hematology PA-Maplewood

Maplewood, Minnesota, United States

Site Status

Regions Hospital

Saint Paul, Minnesota, United States

Site Status

United Hospital

Saint Paul, Minnesota, United States

Site Status

Saint Luke's Hospital of Kansas City

Kansas City, Missouri, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Nebraska Methodist Hospital

Omaha, Nebraska, United States

Site Status

Sparta Cancer Treatment Center

Sparta, New Jersey, United States

Site Status

University of Rochester

Rochester, New York, United States

Site Status

Carolinas Medical Center/Levine Cancer Institute

Charlotte, North Carolina, United States

Site Status

Novant Health Forsyth Medical Center

Winston-Salem, North Carolina, United States

Site Status

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Site Status

Summa Health System - Akron Campus

Akron, Ohio, United States

Site Status

Cleveland Clinic Akron General

Akron, Ohio, United States

Site Status

Summa Health System - Barberton Campus

Barberton, Ohio, United States

Site Status

University of Cincinnati Cancer Center-UC Medical Center

Cincinnati, Ohio, United States

Site Status

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Site Status

University Hospitals Portage Medical Center

Ravenna, Ohio, United States

Site Status

UH Seidman Cancer Center at Salem Regional Medical Center

Salem, Ohio, United States

Site Status

University of Cincinnati Cancer Center-West Chester

West Chester, Ohio, United States

Site Status

Cancer Treatment Center

Wooster, Ohio, United States

Site Status

Natalie Warren Bryant Cancer Center at Saint Francis

Tulsa, Oklahoma, United States

Site Status

Clackamas Radiation Oncology Center

Clackamas, Oregon, United States

Site Status

Legacy Good Samaritan Hospital and Medical Center

Portland, Oregon, United States

Site Status

Providence Portland Medical Center

Portland, Oregon, United States

Site Status

Providence Saint Vincent Medical Center

Portland, Oregon, United States

Site Status

Jefferson Abington Hospital

Abington, Pennsylvania, United States

Site Status

Saint Luke's University Hospital-Bethlehem Campus

Bethlehem, Pennsylvania, United States

Site Status

Bryn Mawr Hospital

Bryn Mawr, Pennsylvania, United States

Site Status

Northeast Radiation Oncology Center

Dunmore, Pennsylvania, United States

Site Status

UPMC Cancer Centers - Arnold Palmer Pavilion

Greensburg, Pennsylvania, United States

Site Status

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

Paoli Memorial Hospital

Paoli, Pennsylvania, United States

Site Status

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

Site Status

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

Site Status

UPMC Washington Hospital Radiation Oncology

Washington, Pennsylvania, United States

Site Status

Reading Hospital

West Reading, Pennsylvania, United States

Site Status

Lankenau Medical Center

Wynnewood, Pennsylvania, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Spartanburg Medical Center

Spartanburg, South Carolina, United States

Site Status

Rapid City Regional Hospital

Rapid City, South Dakota, United States

Site Status

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, United States

Site Status

University of Texas Medical Branch

Galveston, Texas, United States

Site Status

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status

Intermountain Medical Center

Murray, Utah, United States

Site Status

McKay-Dee Hospital Center

Ogden, Utah, United States

Site Status

Utah Valley Regional Medical Center

Provo, Utah, United States

Site Status

Utah Cancer Specialists-Salt Lake City

Salt Lake City, Utah, United States

Site Status

LDS Hospital

Salt Lake City, Utah, United States

Site Status

Saint George Regional Medical Center

St. George, Utah, United States

Site Status

Inova Fairfax Hospital

Falls Church, Virginia, United States

Site Status

Virginia Mason Medical Center

Seattle, Washington, United States

Site Status

Swedish Medical Center-First Hill

Seattle, Washington, United States

Site Status

University of Washington Medical Center - Montlake

Seattle, Washington, United States

Site Status

Compass Oncology Vancouver

Vancouver, Washington, United States

Site Status

Wheeling Hospital/Schiffler Cancer Center

Wheeling, West Virginia, United States

Site Status

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, United States

Site Status

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Aspirus Regional Cancer Center

Wausau, Wisconsin, United States

Site Status

Countries

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United States

Other Identifiers

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NCI-2011-02012

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000665163

Identifier Type: -

Identifier Source: secondary_id

RTOG-0837

Identifier Type: -

Identifier Source: secondary_id

RTOG 0837

Identifier Type: OTHER

Identifier Source: secondary_id

RTOG-0837

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA180868

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10CA021661

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2011-02012

Identifier Type: -

Identifier Source: org_study_id

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