NCT00731731|CompletedPhase 1ResultsDMC

Vorinostat, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme

Phase I/II Study of Vorinostat (Suberoylanilide Hydroxamic Acid [SAHA]), Temozolomide, and Radiation Therapy in Patients With Newly Diagnosed Glioblastoma

National Cancer Institute (NCI)ClinicalTrials.gov

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6 other identifiers

NCI-2009-00672N0874ABTC 0902CDR0000609743U10CA180821U10CA025224

Study Type

interventional

Target

125

Locations

1 country

Sites

110

Timeline

RegisteredAug 2008

StartedJul 2009

CompletionNov 2019

Brief Summary

This phase I/II trial studies the side effects and best dose of vorinostat when given together with temozolomide and radiation therapy and to see how well they work in treating patients with newly diagnosed glioblastoma multiforme. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. 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. Giving vorinostat together with temozolomide and radiation therapy may kill more tumor cells.

Trial Health

On Track

Trial Health Score

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

Enrollment

125

participants targeted

Target at P75+ for phase_1

Timeline

Completed

Started Jul 2009

Longer than P75 for phase_1

Geographic Reach

1 country

110 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

10.3 years study duration

First Submitted

Initial submission to the registry

August 8, 2008

Completed

3 days until next milestone

First Posted

Study publicly available on registry

August 11, 2008

Completed

11 months until next milestone

Study Start

First participant enrolled

July 10, 2009

Completed

4.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 2, 2014

Completed

1.3 years until next milestone

Results Posted

Study results publicly available

May 13, 2015

Completed

4.5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2019

Completed

Last Updated

August 4, 2022

Status Verified

August 1, 2022

Enrollment Period

4.6 years

First QC Date

August 8, 2008

Results QC Date

April 28, 2015

Last Update Submit

August 3, 2022

Conditions

Adult Giant Cell Glioblastoma Adult Glioblastoma Adult Gliosarcoma

Outcome Measures

Primary Outcomes (2)

Maximum Tolerated Dose of Vorinostat, Defined as the Dose at Which Fewer Than One-third of Patients Experience DLTs, Graded According to NCI CTCAE (Common Toxicity Criteria for Adverse Effects) Version 3.0 (Phase I)
The Maximum Tolerated Dose (MTD) will be based on the assessment of Dose Limiting Toxicity (DLT) during the first 10 weeks of treatment only, and will be defined as the dose at which fewer than one-third of patients experience a DLT to vorinostat. The MTD is the dose level at which 0/3 or 1/6 patients experience DLT with the next higher dose having at least 2/3 or 2/6 patients encountering DLT. \> \> DLT will be defined as any of the following events occurring during treatment with vorinostat and temozolomide and attributable to one or both study drugs: * Grade 3 or 4 thrombocytopenia, grade 4 anemia or grade 4 neutropenia lasting \> 7 days * Any non-hematologic grade 3 or greater adverse event, excluding alopecia and venous thromboembolism * Grade 4 radiation-induced skin changes * Failure to recover from toxicities to be eligible for re-treatment with vorinostat and temozolomide ≤ 14 days of the last dose of the two drugs
10 weeks
Overall Survival at 15 Months (Phase II)
The primary endpoint will be survival status at 15 months (OS15). In addition, survival will be estimated using a Kaplan-Meier curve. For this analysis, patients who are still alive at the time of analysis have survival time censored at the last contact date.
Time from study registration to the date of death from any cause, assessed up to 5 years

Secondary Outcomes (3)

Incidence of Adverse Events, Based on CTC (Common Toxicity Criteria) Severity Grade
Up to 5 years
Time to Tumor Progression (Phase II)
Up to 5 years
Incidence of Adverse Events, as Per NCI CTCAE Version 3.0 (Phase II)
Up to 5 years

Study Arms (1)

Treatment (radiation therapy, vorinostat, temozolomide)

EXPERIMENTAL

Patients undergo radiotherapy and receive vorinostat PO QD on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Patients also receive temozolomide PO QD on days 1-42. Beginning 4-6 weeks later, patients receive vorinostat PO QD on days 1-7 and 15-21 and temozolomide PO QD on days 1-5. Treatment with vorinostat and temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Radiation: 3-Dimensional Conformal Radiation TherapyProcedure: Cognitive AssessmentOther: Laboratory Biomarker AnalysisDrug: TemozolomideDrug: Vorinostat

Interventions

3-Dimensional Conformal Radiation TherapyRADIATION

Undergo 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

Treatment (radiation therapy, vorinostat, temozolomide)

Cognitive AssessmentPROCEDURE

Ancillary studies

Treatment (radiation therapy, vorinostat, temozolomide)

Laboratory Biomarker AnalysisOTHER

Correlative studies

Treatment (radiation therapy, vorinostat, temozolomide)

TemozolomideDRUG

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

Treatment (radiation therapy, vorinostat, temozolomide)

VorinostatDRUG

Given PO

Also known as: L-001079038, MSK-390, SAHA, Suberanilohydroxamic Acid, Suberoylanilide Hydroxamic Acid, Zolinza

Treatment (radiation therapy, vorinostat, temozolomide)

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

PRE-REGISTRATION:
Central pathology review submission; this review is mandatory prior to registration to confirm eligibility; it should be initiated as soon after surgery as possible
Treatment should begin \>= 2 weeks and =\< 5 weeks following surgery
REGISTRATION:
Histologically confirmed glioblastoma multiforme as determined by pre-registration central pathology review; Note: gliosarcomas and other grade 4 astrocytoma variants (e.g., giant cell) are eligible
Measurable or evaluable disease by gadolinium magnetic resonance imaging (MRI) or contrast computed tomography (CT) scan; Note: patients who have had a gross total resection (GTR) are eligible on the basis of evaluable disease
Must begin partial brain radiotherapy on the same day that vorinostat and temozolomide begin
Karnofsky performance status of \>= 60
Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
Absolute neutrophil count (ANC) \>= 1,500/mm\^3
Platelet count \>= 100,000/mm\^3
White blood cell (WBC) \>= 3,000/mm\^3
Hemoglobin \>= 10.0 g/dL; Note: this level may be reached by transfusion
Total bilirubin =\< 2.0 x institutional upper limit of normal (ULN)
Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\]) =\< 2.0 x ULN
+8 more criteria

You may not qualify if:

Any of the following:
Pregnant women
Nursing women
Men or women of childbearing potential who are unwilling to employ adequate contraception throughout the duration of the study and for 12 weeks after treatment has ended
Prior cytotoxic drug therapy, non-cytotoxic drug therapy, or experimental drug therapy for brain tumors
Prior cranial RT
Prior Gliadel wafers
Known hypersensitivity to any of the components of vorinostat or other agents used in study
Valproic acid, another histone deacetylase inhibitor, =\< 2 weeks prior to registration and during treatment
Other active malignancy =\< 3 years prior to registration; Exception: non-melanotic skin cancer or carcinoma in situ of the cervix; Note: if there is a history of prior malignancy, they must not be receiving other specific treatment (other than hormonal therapy) for their cancer
Uncontrolled infection
Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy; Note: patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial
Co-morbid systemic illness or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with proper assessment of safety and adverse events of the prescribed regimens
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements
History of myocardial infarction or unstable angina =\< 6 months prior to registration or congestive heart failure (CHF) requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
+11 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

National Cancer Institute (NCI)lead

Study Sites (110)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

UCSF Medical Center-Parnassus

San Francisco, California, 94143, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

AdventHealth Orlando

Orlando, Florida, 32803, United States

Location

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Hawaii Cancer Care Inc - Waterfront Plaza

Honolulu, Hawaii, 96813, United States

Location

Queen's Medical Center

Honolulu, Hawaii, 96813, United States

Location

Straub Clinic and Hospital

Honolulu, Hawaii, 96813, United States

Location

University of Hawaii Cancer Center

Honolulu, Hawaii, 96813, United States

Location

Kuakini Medical Center

Honolulu, Hawaii, 96817, United States

Location

Queen's Cancer Center - Kuakini

Honolulu, Hawaii, 96817, United States

Location

The Cancer Center of Hawaii-Liliha

Honolulu, Hawaii, 96817, United States

Location

Kapiolani Medical Center for Women and Children

Honolulu, Hawaii, 96826, United States

Location

Castle Medical Center

Kailua, Hawaii, 96734, United States

Location

Wilcox Memorial Hospital and Kauai Medical Clinic

Lihue, Hawaii, 96766, United States

Location

Pali Momi Medical Center

‘Aiea, Hawaii, 96701, United States

Location

Queen's Cancer Center - Pearlridge

‘Aiea, Hawaii, 96701, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Presence Resurrection Medical Center

Chicago, Illinois, 60631, United States

Location

Garneau, Stewart C MD (UIA Investigator)