NCT01062425

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
261

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Feb 2010

Longer than P75 for phase_2

Geographic Reach
1 country

105 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 3, 2010

Completed
1 day until next milestone

First Posted

Study publicly available on registry

February 4, 2010

Completed
22 days until next milestone

Study Start

First participant enrolled

February 26, 2010

Completed
5.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 6, 2015

Completed
10 months until next milestone

Results Posted

Study results publicly available

September 19, 2016

Completed
5.7 years until next milestone

Study Completion

Last participant's last visit for all outcomes

May 20, 2022

Completed
Last Updated

July 26, 2022

Status Verified

May 1, 2022

Enrollment Period

5.8 years

First QC Date

February 3, 2010

Results QC Date

July 28, 2016

Last Update Submit

June 28, 2022

Conditions

Outcome Measures

Primary Outcomes (1)

  • 6-month Progression-free Survival Rate

    Six-month progression-free survival is the rate of patients who have NOT progressed at six months, where progressive disease is defined as any of the following: ≥ 25% increase in sum of the products of perpendicular diameters of enhancing lesions; any new lesion; or clinical deterioration. Progression will be determined by central review of MRI exams, assessed using MacDonald criteria for progression versus response on 2D T1 and T2 weighted images.

    From randomization to 6 months.

Secondary Outcomes (3)

  • Overall Survival (OS)

    From randomization to time of death due to any cause. Patients are followed until death. Analysis occurs after all patients have been potentially followed for six months.

  • Progression-free Survival (PFS)

    From randomization to time of first progression or death due to any cause. Patients are followed until death. Analysis occurs after all patients have been potentially followed for six months.

  • Incidence of Grade 3+ Toxicities

    From randomization to six months.

Study Arms (2)

Cediranib, TMZ, and RT

EXPERIMENTAL

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.

Radiation: 3-Dimensional Conformal Radiation TherapyDrug: Cediranib MaleateRadiation: Intensity-Modulated Radiation TherapyOther: Laboratory Biomarker AnalysisDrug: Temozolomide

Placebo, TMZ, and RT

ACTIVE COMPARATOR

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.

Radiation: 3-Dimensional Conformal Radiation TherapyRadiation: Intensity-Modulated Radiation TherapyOther: Laboratory Biomarker AnalysisOther: Placebo AdministrationDrug: Temozolomide

Interventions

Undergo 3-dimensional conformal radiotherapy

Also known as: 3-dimensional radiation therapy, 3D Conformal, 3D CONFORMAL RADIATION THERAPY, 3D CRT, 3D-CRT, Conformal Therapy, Radiation Conformal Therapy, Radiation, 3D Conformal
Cediranib, TMZ, and RTPlacebo, TMZ, and RT

Given PO

Also known as: AZD2171, AZD2171 Maleate, Recentin
Cediranib, TMZ, and RT

Undergo intensity-modulated radiation therapy

Also known as: IMRT, Intensity Modulated RT, Intensity-Modulated Radiotherapy, Radiation, Intensity-Modulated Radiotherapy
Cediranib, TMZ, and RTPlacebo, TMZ, and RT

Correlative studies

Cediranib, TMZ, and RTPlacebo, TMZ, and RT

Given PO

Placebo, TMZ, and RT

Given PO

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, TMZ
Cediranib, TMZ, and RTPlacebo, TMZ, and RT

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • +13 more criteria

You may not qualify if:

  • 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
  • +14 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (105)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, 35233, United States

Location

The Kirklin Clinic at Acton Road

Birmingham, Alabama, 35243, United States

Location

Arizona Oncology Services Foundation

Scottsdale, Arizona, 85260, United States

Location

Banner University Medical Center - Tucson

Tucson, Arizona, 85719, United States

Location

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

Saint Joseph Hospital - Orange

Orange, California, 92868, United States

Location

Poudre Valley Hospital

Fort Collins, Colorado, 80524, United States

Location

Smilow Cancer Hospital Care Center at Saint Francis

Hartford, Connecticut, 06105, United States

Location

The Hospital of Central Connecticut

New Britain, Connecticut, 06050, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

Christiana Care Health System-Christiana Hospital

Newark, Delaware, 19718, United States

Location

AdventHealth Orlando

Orlando, Florida, 32803, United States

Location

Bay Medical Center

Panama City, Florida, 32401, United States

Location

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

Location

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Queen's Medical Center

Honolulu, Hawaii, 96813, United States

Location

University of Hawaii Cancer Center

Honolulu, Hawaii, 96813, United States

Location

The Cancer Center of Hawaii-Liliha

Honolulu, Hawaii, 96817, United States

Location

Saint Alphonsus Cancer Care Center-Boise

Boise, Idaho, 83706, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

OSF Saint Francis Medical Center

Peoria, Illinois, 61637, United States

Location

Carle Cancer Center

Urbana, Illinois, 61801, United States

Location

Radiation Oncology Associates PC

Fort Wayne, Indiana, 46804, United States

Location

Parkview Hospital Randallia

Fort Wayne, Indiana, 46805, United States

Location

IU Health Methodist Hospital

Indianapolis, Indiana, 46202, United States

Location

University of Kansas Cancer Center

Kansas City, Kansas, 66160, United States

Location

Kansas City NCI Community Oncology Research Program

Prairie Village, Kansas, 66208, United States

Location

Baptist Health Lexington

Lexington, Kentucky, 40503, United States

Location

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, 40536, United States

Location

Maine Medical Center- Scarborough Campus

Scarborough, Maine, 04074, United States

Location

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Saint Joseph Mercy Hospital

Ann Arbor, Michigan, 48106, United States

Location

Henry Ford Macomb Hospital-Clinton Township

Clinton Township, Michigan, 48038, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Ascension Saint John Hospital

Detroit, Michigan, 48236, United States

Location

Genesys Regional Medical Center-West Flint Campus

Flint, Michigan, 48532, United States

Location

West Michigan Cancer Center

Kalamazoo, Michigan, 49007, United States

Location

Sparrow Hospital

Lansing, Michigan, 48912, United States

Location

Saint Joseph Mercy Oakland

Pontiac, Michigan, 48341, United States

Location

Lake Huron Medical Center

Port Huron, Michigan, 48060, United States

Location

Ascension Saint Mary's Hospital

Saginaw, Michigan, 48601, United States

Location

Saint John Macomb-Oakland Hospital

Warren, Michigan, 48093, United States

Location

Mercy Hospital

Coon Rapids, Minnesota, 55433, United States

Location

Minnesota Oncology Hematology PA-Maplewood

Maplewood, Minnesota, 55109, United States

Location

Regions Hospital

Saint Paul, Minnesota, 55101, United States

Location

United Hospital

Saint Paul, Minnesota, 55102, United States

Location

Saint Luke's Hospital of Kansas City

Kansas City, Missouri, 64111, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Nebraska Methodist Hospital

Omaha, Nebraska, 68114, United States

Location

Sparta Cancer Treatment Center

Sparta, New Jersey, 07871, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Carolinas Medical Center/Levine Cancer Institute

Charlotte, North Carolina, 28203, United States

Location

Novant Health Forsyth Medical Center

Winston-Salem, North Carolina, 27103, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

Summa Health System - Akron Campus

Akron, Ohio, 44304, United States

Location

Cleveland Clinic Akron General

Akron, Ohio, 44307, United States

Location

Summa Health System - Barberton Campus

Barberton, Ohio, 44203, United States

Location

University of Cincinnati Cancer Center-UC Medical Center

Cincinnati, Ohio, 45219, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

University Hospitals Portage Medical Center

Ravenna, Ohio, 44266, United States

Location

UH Seidman Cancer Center at Salem Regional Medical Center

Salem, Ohio, 44460, United States

Location

University of Cincinnati Cancer Center-West Chester

West Chester, Ohio, 45069, United States

Location

Cancer Treatment Center

Wooster, Ohio, 44691, United States

Location

Natalie Warren Bryant Cancer Center at Saint Francis

Tulsa, Oklahoma, 74136, United States

Location

Clackamas Radiation Oncology Center

Clackamas, Oregon, 97015, 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

Providence Saint Vincent Medical Center

Portland, Oregon, 97225, United States

Location

Jefferson Abington Hospital

Abington, Pennsylvania, 19001, United States

Location

Saint Luke's University Hospital-Bethlehem Campus

Bethlehem, Pennsylvania, 18015, United States

Location

Bryn Mawr Hospital

Bryn Mawr, Pennsylvania, 19010, United States

Location

Northeast Radiation Oncology Center

Dunmore, Pennsylvania, 18512, United States

Location

UPMC Cancer Centers - Arnold Palmer Pavilion

Greensburg, Pennsylvania, 15601, United States

Location

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, 17033-0850, United States

Location

Paoli Memorial Hospital

Paoli, Pennsylvania, 19301, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

UPMC Washington Hospital Radiation Oncology

Washington, Pennsylvania, 15301, United States

Location

Reading Hospital

West Reading, Pennsylvania, 19611, United States

Location

Lankenau Medical Center

Wynnewood, Pennsylvania, 19096, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Spartanburg Medical Center

Spartanburg, South Carolina, 29303, United States

Location

Rapid City Regional Hospital

Rapid City, South Dakota, 57701, United States

Location

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, 75390, United States

Location

University of Texas Medical Branch

Galveston, Texas, 77555-0565, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, 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

Utah Cancer Specialists-Salt Lake City

Salt Lake City, Utah, 84106, United States

Location

LDS Hospital

Salt Lake City, Utah, 84143, United States

Location

Saint George Regional Medical Center

St. George, Utah, 84770, United States

Location

Inova Fairfax Hospital

Falls Church, Virginia, 22042, United States

Location

Virginia Mason Medical Center

Seattle, Washington, 98101, United States

Location

Swedish Medical Center-First Hill

Seattle, Washington, 98122-4307, United States

Location

University of Washington Medical Center - Montlake

Seattle, Washington, 98195, United States

Location

Compass Oncology Vancouver

Vancouver, Washington, 98684, United States

Location

Wheeling Hospital/Schiffler Cancer Center

Wheeling, West Virginia, 26003, United States

Location

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Aspirus Regional Cancer Center

Wausau, Wisconsin, 54401, United States

Location

MeSH Terms

Conditions

GlioblastomaGliosarcoma

Interventions

Radiotherapy, ConformalcediranibRadiotherapy, Intensity-ModulatedTemozolomide

Condition Hierarchy (Ancestors)

AstrocytomaGliomaNeoplasms, NeuroepithelialNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Glandular and EpithelialNeoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Radiotherapy, Computer-AssistedRadiotherapyTherapeuticsDacarbazineTriazenesOrganic ChemicalsImidazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Results Point of Contact

Title
Wendy Seiferheld, M.S.
Organization
NRG Oncology

Study Officials

  • Tracy T Batchelor

    NRG Oncology

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 3, 2010

First Posted

February 4, 2010

Study Start

February 26, 2010

Primary Completion

December 6, 2015

Study Completion

May 20, 2022

Last Updated

July 26, 2022

Results First Posted

September 19, 2016

Record last verified: 2022-05

Locations