Phase I/II Study of Vorinostat (Suberoylanilide Hydroxamic Acid [SAHA]), Temozolomide, and Radiation Therapy in Patients With Newly Diagnosed Glioblastoma
I. To determine the maximum tolerated dose of vorinostat when administered with temozolomide
and radiotherapy in patients with newly diagnosed glioblastoma multiforme. (Phase I) II. To
determine the efficacy of this regimen, in terms of overall survival, in these patients.
I. To determine the toxicity of this regimen in these patients. (Phase I) II. To determine
progression-free survival of patients treated with this regimen. (Phase II) III. To further
evaluate the safety profile of this regimen in these patients. (Phase II) IV. To determine
the neurocognitive effects in these patients and correlate the results with outcome
endpoints. (Phase II)
I. To correlate tumor molecular characteristics and expression profile with outcome.
II. To evaluate potential mechanisms of therapy resistance in tumor samples obtained at the
time of tumor progression.
OUTLINE: This is a multicenter, phase I, dose-escalation study of vorinostat followed by a
phase II study.
Patients undergo radiotherapy and receive oral vorinostat once daily on days 1-5, 8-12,
15-19, 22-26, 29-33, and 36-40. Patients also receive oral temozolomide once daily on days
1-42. Beginning 4-6 weeks later, patients receive oral vorinostat once daily on days 1-7
and 15-21 and oral temozolomide once daily 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.
Patients enrolled in phase II and those who are treated at the maximum tolerated dose in
phase I submit tumor tissue samples for correlative laboratory studies. Studies include
assessment of histone acetylation status by immunohistochemistry; gene expression profiling;
and assessment of MGMT methylation status by polymerase chain reaction. Patients enrolled in
phase II and those who are treated at the maximum tolerated dose in phase I complete a
neurocognitive assessment prior to, during, and after completion of study therapy. The
assessment includes the Hopkins Verbal Learning Test (HVLT-R) (Revised), the Controlled Oral
Word Association test from the Multilingual Aphasia Examination (COWA), the Trail Making
Test A: Visual scanning speed, and the Trail Making Test B: Divided attention.
After completion of study treatment, patients are followed every 3 months for 2 years and
then every 6 months for 1 year.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose of vorinostat, defined as the dose at which fewer than one-third of patients experience DLTs, graded according to NCI CTCAE version 3.0 (Phase I)
North Central Cancer Treatment Group
United States: Food and Drug Administration
|Henry Ford Hospital||Detroit, Michigan 48202|
|Dana-Farber Cancer Institute||Boston, Massachusetts 02115|
|Munson Medical Center||Traverse City, Michigan 49684|
|MeritCare Medical Group||Fargo, North Dakota 58122|
|Rice Memorial Hospital||Willmar, Minnesota 56201|
|Queen's Medical Center||Honolulu, Hawaii 96813|
|University of Pittsburgh||Pittsburgh, Pennsylvania 15261|
|Kapiolani Medical Center at Pali Momi||Aiea, Hawaii 96701|
|Kapiolani Medical Center for Women and Children||Honolulu, Hawaii 96826|
|Straub Clinic and Hospital||Honolulu, Hawaii 96813|
|Hawaii Medical Center East||Honolulu, Hawaii 96817|
|Castle Medical Center||Kailua, Hawaii 96734|
|Oncare Hawaii Inc-POB II||Honolulu, Hawaii 96813|
|Oncare Hawaii Inc-Kuakini||Honolulu, Hawaii 96817|
|Resurrection Healthcare||Chicago, Illinois 60631|
|Merit Care Clinic Bemidji||Bemidji, Minnesota 56601|
|Meritcare Hospital||Fargo, North Dakota 58122|
|Sanford University of South Dakota Medical Center||Sioux Falls, South Dakota 57117-5134|
|Kuakini Medical Center||Honolulu, Hawaii 96817|
|Wilcox Memorial Hospital and Kauai Medical Clinic||Lihue, Hawaii 96766-1099|
|Oncare Hawaii Inc - Kapiolani Medical Center at Pali Momi||Aiea, Hawaii 96701|