Adult GlioblastomaPhase 2NCT01062425
Temozolomide and Radiation Therapy With or Without Cediranib Maleate in Treating Patients With Newly Diagnosed Glioblastoma
A Phase 2 study testing 3-Dimensional Conformal Radiation Therapy, Cediranib Maleate and Intensity-Modulated Radiation Therapy in people with Adult Glioblastoma and Adult Gliosarcoma, run by National Cancer Institute (NCI) at 105 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adult Glioblastoma, Adult Gliosarcoma
- What is being tested?
- 3-Dimensional Conformal Radiation Therapy, Cediranib Maleate and Intensity-Modulated Radiation Therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 261 participants
- Where
- 105 sitesUnited States
- Study dates
- 26 Feb 2010to 20 May 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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:
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- 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
Trial locations and contacts
105 sites in 1 country.
105 sites in 1 country
United States105 sites
Jefferson Abington Hospital
Abington, Pennsylvania, 19001
Summa Health System - Akron Campus
Akron, Ohio, 44304
Cleveland Clinic Akron General
Akron, Ohio, 44307
Saint Joseph Mercy Hospital
Ann Arbor, Michigan, 48106
Emory University Hospital Midtown
Atlanta, Georgia, 30308
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, 21201
Summa Health System - Barberton Campus
Barberton, Ohio, 44203
Saint Luke's University Hospital-Bethlehem Campus
Bethlehem, Pennsylvania, 18015
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233
The Kirklin Clinic at Acton Road
Birmingham, Alabama, 35243
Saint Alphonsus Cancer Care Center-Boise
Boise, Idaho, 83706
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Bryn Mawr Hospital
Bryn Mawr, Pennsylvania, 19010
Medical University of South Carolina
Charleston, South Carolina, 29425
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, 28203
Northwestern University
Chicago, Illinois, 60611
Rush University Medical Center
Chicago, Illinois, 60612
University of Cincinnati Cancer Center-UC Medical Center
Cincinnati, Ohio, 45219
Clackamas Radiation Oncology Center
Clackamas, Oregon, 97015
Henry Ford Macomb Hospital-Clinton Township
Clinton Township, Michigan, 48038
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
Mercy Hospital
Coon Rapids, Minnesota, 55433
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390
Henry Ford Hospital
Detroit, Michigan, 48202
Ascension Saint John Hospital
Detroit, Michigan, 48236
City of Hope Comprehensive Cancer Center
Duarte, California, 91010
Northeast Radiation Oncology Center
Dunmore, Pennsylvania, 18512
Inova Fairfax Hospital
Falls Church, Virginia, 22042
Genesys Regional Medical Center-West Flint Campus
Flint, Michigan, 48532
Poudre Valley Hospital
Fort Collins, Colorado, 80524
Radiation Oncology Associates PC
Fort Wayne, Indiana, 46804
Parkview Hospital Randallia
Fort Wayne, Indiana, 46805
University of Texas Medical Branch
Galveston, Texas, 77555-0565
UPMC Cancer Centers - Arnold Palmer Pavilion
Greensburg, Pennsylvania, 15601
Smilow Cancer Hospital Care Center at Saint Francis
Hartford, Connecticut, 06105
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, 17033-0850
Queen's Medical Center
Honolulu, Hawaii, 96813
University of Hawaii Cancer Center
Honolulu, Hawaii, 96813
The Cancer Center of Hawaii-Liliha
Honolulu, Hawaii, 96817
IU Health Methodist Hospital
Indianapolis, Indiana, 46202
West Michigan Cancer Center
Kalamazoo, Michigan, 49007
University of Kansas Cancer Center
Kansas City, Kansas, 66160
Saint Luke's Hospital of Kansas City
Kansas City, Missouri, 64111
Sparrow Hospital
Lansing, Michigan, 48912
Baptist Health Lexington
Lexington, Kentucky, 40503
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536
University of Wisconsin Carbone Cancer Center
Madison, Wisconsin, 53792
Minnesota Oncology Hematology PA-Maplewood
Maplewood, Minnesota, 55109
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Intermountain Medical Center
Murray, Utah, 84107
The Hospital of Central Connecticut
New Britain, Connecticut, 06050
Yale University
New Haven, Connecticut, 06520
Christiana Care Health System-Christiana Hospital
Newark, Delaware, 19718
McKay-Dee Hospital Center
Ogden, Utah, 84403
Nebraska Methodist Hospital
Omaha, Nebraska, 68114
Saint Joseph Hospital - Orange
Orange, California, 92868
AdventHealth Orlando
Orlando, Florida, 32803
Bay Medical Center
Panama City, Florida, 32401
Paoli Memorial Hospital
Paoli, Pennsylvania, 19301
OSF Saint Francis Medical Center
Peoria, Illinois, 61637
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107
Allegheny General Hospital
Pittsburgh, Pennsylvania, 15212
Saint Joseph Mercy Oakland
Pontiac, Michigan, 48341
Lake Huron Medical Center
Port Huron, Michigan, 48060
Legacy Good Samaritan Hospital and Medical Center
Portland, Oregon, 97210
Providence Portland Medical Center
Portland, Oregon, 97213
Providence Saint Vincent Medical Center
Portland, Oregon, 97225
Kansas City NCI Community Oncology Research Program
Prairie Village, Kansas, 66208
Utah Valley Regional Medical Center
Provo, Utah, 84604
Rapid City Regional Hospital
Rapid City, South Dakota, 57701
University Hospitals Portage Medical Center
Ravenna, Ohio, 44266
University of Rochester
Rochester, New York, 14642
Ascension Saint Mary's Hospital
Saginaw, Michigan, 48601
Regions Hospital
Saint Paul, Minnesota, 55101
United Hospital
Saint Paul, Minnesota, 55102
UH Seidman Cancer Center at Salem Regional Medical Center
Salem, Ohio, 44460
Utah Cancer Specialists-Salt Lake City
Salt Lake City, Utah, 84106
LDS Hospital
Salt Lake City, Utah, 84143
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229
Maine Medical Center- Scarborough Campus
Scarborough, Maine, 04074
Arizona Oncology Services Foundation
Scottsdale, Arizona, 85260
Virginia Mason Medical Center
Seattle, Washington, 98101
Swedish Medical Center-First Hill
Seattle, Washington, 98122-4307
University of Washington Medical Center - Montlake
Seattle, Washington, 98195
Sparta Cancer Treatment Center
Sparta, New Jersey, 07871
Spartanburg Medical Center
Spartanburg, South Carolina, 29303
Washington University School of Medicine
St Louis, Missouri, 63110
Saint George Regional Medical Center
St. George, Utah, 84770
Banner University Medical Center - Tucson
Tucson, Arizona, 85719
Natalie Warren Bryant Cancer Center at Saint Francis
Tulsa, Oklahoma, 74136
Carle Cancer Center
Urbana, Illinois, 61801
Compass Oncology Vancouver
Vancouver, Washington, 98684
Saint John Macomb-Oakland Hospital
Warren, Michigan, 48093
UPMC Washington Hospital Radiation Oncology
Washington, Pennsylvania, 15301
Aspirus Regional Cancer Center
Wausau, Wisconsin, 54401
University of Cincinnati Cancer Center-West Chester
West Chester, Ohio, 45069
Reading Hospital
West Reading, Pennsylvania, 19611
Wheeling Hospital/Schiffler Cancer Center
Wheeling, West Virginia, 26003
Novant Health Forsyth Medical Center
Winston-Salem, North Carolina, 27103
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
Cancer Treatment Center
Wooster, Ohio, 44691
Lankenau Medical Center
Wynnewood, Pennsylvania, 19096
About this study
Official title: Randomized, Phase II, Double-Blind, Placebo-Controlled Trial of Conventional Chemoradiation and Adjuvant Temozolomide Plus Cediranib Versus Conventional Chemoradiation and Adjuvant Temozolomide Plus Placebo in Patients With Newly Diagnosed Glioblastoma
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- 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
- Adult Glioblastoma, Adult Gliosarcoma
- Being tested
- 3-Dimensional Conformal Radiation Therapy, Cediranib Maleate, Intensity-Modulated Radiation Therapy, Laboratory Biomarker Analysis, Placebo Administration
- Medical subject headings
- Glioblastoma, Gliosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
3-Dimensional Conformal Radiation TherapyRadiation
Also called 3-dimensional radiation therapy, 3D Conformal, 3D CONFORMAL RADIATION THERAPY, 3D CRT
Undergo 3-dimensional conformal radiotherapy
Cediranib MaleateDrug
Also called AZD2171, AZD2171 Maleate, Recentin
Given PO
Intensity-Modulated Radiation TherapyRadiation
Also called IMRT, Intensity Modulated RT, Intensity-Modulated Radiotherapy, Radiation, Intensity-Modulated Radiotherapy
Undergo intensity-modulated radiation therapy
Laboratory Biomarker AnalysisOther
Correlative studies
Placebo AdministrationOther
Given PO
TemozolomideDrug
Also called 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
Given PO
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Radiation: 3-Dimensional Conformal Radiation Therapy; Drug: Cediranib Maleate; Radiation: Intensity-Modulated Radiation Therapy; Other: Laboratory Biomarker Analysis; Drug: 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. Receives: Radiation: 3-Dimensional Conformal Radiation Therapy; Radiation: Intensity-Modulated Radiation Therapy; Other: Laboratory Biomarker Analysis; Other: Placebo Administration; Drug: Temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From randomization to 6 months.
Secondary outcomes (3)
Overall Survival (OS)
OS will be estimated using the Kaplan-Meier method and differences between treatment arms will be tested using the log rank test. Multivariate analyses with the Cox proportional hazard model for OS will be performed with the stratification variables as fixed variables to assess the treatment effect adjusting patient-specific risk factors.
Measured: 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)
Progression-free survival time is defined as time from randomization to date of first progression or death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive without progression are censored at the date of last contact. Progression 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.
Measured: 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
The number of patients with reported grade 3 and higher treatment-related toxicities as assessed by Common Terminology Criteria for Adverse Events version 4.0
Measured: From randomization to six months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Feb 2010 (estimated)
- Study start26 Feb 2010
- Primary completion6 Dec 2015
- Study completion20 May 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Adult GlioblastomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 261 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Collaborators
- NRG Oncology, Radiation Therapy Oncology Group
- Responsible party
- Sponsor
- Investigators
- Tracy T Batchelor, Principal investigator, NRG Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01062425
- Sponsor's protocol ID
- NCI-2011-02012
- Other IDs
- NCI-2011-02012, CDR0000665163, RTOG-0837, RTOG 0837, RTOG-0837, U10CA180868, U10CA021661
- Status last verified
- May 2022
- First submitted
- 3 Feb 2010
- Last updated
- 26 Jul 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Phase II, Double-Blind, Placebo-Controlled Trial of Conventional Chemoradiation and Adjuvant Temozolomide Plus Cediranib Versus Conventional Chemoradiation and Adjuvant Temozolomide Plus Placebo in Patients With Newly Diagnosed Glioblastoma
- ClinicalTrials.gov ID
- NCT01062425
- Acronym / sponsor ID
- NCI-2011-02012
- Conditions
- Adult Glioblastoma, Adult Gliosarcoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 261 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Collaborators
- NRG Oncology, Radiation Therapy Oncology Group
- Study start
- 26 Feb 2010 (actual)
- Primary completion
- 6 Dec 2015 (actual)
- Study completion
- 20 May 2022 (actual)
- First posted
- 4 Feb 2010 (estimated)
- Results
- Posted 19 Sep 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
PRIMARY OBJECTIVES:
- 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:
- 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.
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cediranib, TMZ, and RT | Experimental | Radiation: 3-Dimensional Conformal Radiation Therapy, Drug: Cediranib Maleate, Radiation: Intensity-Modulated Radiation Therapy, Other: Laboratory Biomarker Analysis, Drug: TemozolomideCediranib (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. |
| Placebo, TMZ, and RT | Active comparator | Radiation: 3-Dimensional Conformal Radiation Therapy, Radiation: Intensity-Modulated Radiation Therapy, Other: Laboratory Biomarker Analysis, Other: Placebo Administration, Drug: TemozolomidePlacebo (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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (28 listed)
- 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
- 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
Key exclusion criteria (29 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 3-Dimensional Conformal Radiation TherapyAlso: 3-dimensional radiation therapy, 3D Conformal, 3D CONFORMAL RADIATION THERAPY, 3D CRTUndergo 3-dimensional conformal radiotherapy | Radiation | Cediranib, TMZ, and RT, Placebo, TMZ, and RT |
| Cediranib MaleateAlso: AZD2171, AZD2171 Maleate, RecentinGiven PO | Drug | Cediranib, TMZ, and RT |
| Intensity-Modulated Radiation TherapyAlso: IMRT, Intensity Modulated RT, Intensity-Modulated Radiotherapy, Radiation, Intensity-Modulated RadiotherapyUndergo intensity-modulated radiation therapy | Radiation | Cediranib, TMZ, and RT, Placebo, TMZ, and RT |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Cediranib, TMZ, and RT, Placebo, TMZ, and RT |
| Placebo AdministrationGiven PO | Other | Placebo, TMZ, and RT |
| TemozolomideAlso: 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 39831Given PO | Drug | Cediranib, TMZ, and RT, Placebo, TMZ, and RT |
Primary outcome
6-month Progression-free Survival Rate
Time frame: From randomization to 6 months.
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.
3 secondary outcomes
Overall Survival (OS)
Time frame: 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)
Time frame: 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
Time frame: From randomization to six months.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jul 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tracy T Batchelor principal investigator
NRG Oncology
105 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 3-Dimensional Conformal Radiation Therapy, Cediranib Maleate and Intensity-Modulated Radiation Therapy in people with Adult Glioblastoma and Adult Gliosarcoma, run by National Cancer Institute (NCI) at 105 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 28 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 105 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Sep 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
6-month Progression-free Survival Rate (time frame: From randomization to 6 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jul 2022.