Vorinostat in Treating Patients With Progressive or Recurrent Glioblastoma Multiforme - Full Text View

Sponsors and Collaborators:	North Central Cancer Treatment Group National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00238303

Purpose

RATIONALE: Drugs used in chemotherapy, such as vorinostat, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vorinostat may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving vorinostat before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving it after surgery may kill any remaining tumor cells.

PURPOSE: This phase II trial is studying how well vorinostat works in treating patients with progressive or recurrent glioblastoma multiforme.

Condition	Intervention	Phase
Brain and Central Nervous System Tumors	Drug: vorinostat Procedure: conventional surgery	Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	Phase II Trial of Suberoylanilide Hydroxamic Acid (SAHA) in Patients With Recurrent Glioblastoma

Resource links provided by NLM:

MedlinePlus related topics: Cancer Surgery

Drug Information available for: Suberoylanilide hydroxamic acid

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

6-month progression-free survival [ Designated as safety issue: No ]

Estimated Enrollment:	94
Study Start Date:	September 2005
Estimated Primary Completion Date:	November 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Stratum 1 (not undergoing surgery): Experimental Patients receive oral vorinostat (SAHA) twice daily for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.	Drug: vorinostat Given orally
Stratum 2 (undergoing surgery): Experimental Beginning 3 days prior to surgery, patients receive oral SAHA once or twice daily for a total of 6 doses. Patients then undergo surgery to remove the tumor. Beginning within 1-4 weeks after surgery, patients receive oral SAHA twice daily for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.	Drug: vorinostat Given orally Procedure: conventional surgery Patients undergo surgery to remove tumor.

Detailed Description:

OBJECTIVES:

Primary

Determine the efficacy of vorinostat (SAHA), in terms of 6-month progression-free survival, in patients with progressive or recurrent glioblastoma multiforme.
Determine the safety and toxicity of this drug in these patients.

Secondary

Determine the pharmacokinetics of this drug in these patients.
Determine the biologic effect of this drug in target tissues, including primary tumor tissue, in these patients.
Correlate genetic alteration of tumors with response in patients treated with this drug.

OUTLINE: This is an open-label, multicenter study. Patients are stratified according to planned surgery (yes [stratum 1] vs no [stratum 2]) and number of prior chemotherapy regimens for progressive/recurrent disease (≤ 1 [stratum 1A] vs ≥ 2 [stratum 1B]).

Stratum 1 (not undergoing surgery): Patients receive oral vorinostat (SAHA) twice daily for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
Stratum 2 (undergoing surgery): Beginning 3 days prior to surgery, patients receive oral SAHA once or twice daily for a total of 6 doses. Patients then undergo surgery to remove the tumor. Beginning within 1-4 weeks after surgery, patients receive oral SAHA twice daily for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically for up to 5 years.

PROJECTED ACCRUAL: A total of 94 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed grade 4 astrocytoma (glioblastoma multiforme), including gliosarcoma, at primary diagnosis or recurrence
- Progressive or recurrent disease
Measurable or evaluable disease by MRI or CT scan

PATIENT CHARACTERISTICS:

Performance status

ECOG 0-2

Life expectancy

Not specified

Hematopoietic

WBC ≥ 3,000/mm^3
Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Hemoglobin ≥ 8 g/dL

Hepatic

AST ≤ 3 times upper limit of normal (ULN)
Bilirubin normal

Renal

Creatinine ≤ 1.5 times ULN

Cardiovascular

No myocardial infarction within the past 6 months
No congestive heart failure
No life-threatening ventricular arrhythmia requiring ongoing maintenance therapy

Immunologic

No known HIV positivity
Not immunocompromised except if related to the use of corticosteroids
No known hypersensitivity to any of the components of the study drug
No uncontrolled infection

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 6 months after completion of study treatment
No other malignancy
No other severe disease that would preclude study participation

PRIOR CONCURRENT THERAPY:

Chemotherapy

Prior adjuvant chemotherapy allowed
More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)
More than 2 weeks since prior small molecule cell cycle inhibitor

Endocrine therapy

Concurrent corticosteroids allowed as long as dose has been stable for ≥ 1 week

Radiotherapy

At least 8 weeks since prior radiotherapy
- Must have evidence of tumor progression by MRI or CT scan after radiotherapy
More than 6 weeks since prior stereotactic radiosurgery or interstitial brachytherapy, unless 1 of the following criteria is met:
- There is a separate lesion by MRI outside of the prior treatment field
- There is evidence of recurrent disease by biopsy, MRI spectroscopy, or positron-emission tomography scan

Other

More than 2 weeks since prior valproic acid

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00238303

Show 106 Study Locations

Sponsors and Collaborators

North Central Cancer Treatment Group

National Cancer Institute (NCI)

Investigators

Study Chair:	Evanthia Galanis, MD	Mayo Clinic
Investigator:	John F. Schwerkoske, MD	Minnesota Oncology Hematology, PA - St. Paul
Investigator:	Kurt A. Jaeckle, MD	Mayo Clinic
Investigator:	Jan C. Buckner, MD	Mayo Clinic

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

Galanis E, Jaeckle KA, Maurer MJ, Reid JM, Ames MM, Hardwick JS, Reilly JF, Loboda A, Nebozhyn M, Fantin VR, Richon VM, Scheithauer B, Giannini C, Flynn PJ, Moore DF Jr, Zwiebel J, Buckner JC. Phase II Trial of Vorinostat in Recurrent Glioblastoma Multiforme: A North Central Cancer Treatment Group Study. J Clin Oncol. 2009 Mar 23; [Epub ahead of print]

Galanis E, Jaeckle KA, Maurer MJ, et al.: N047B: NCCTG phase II trial of vorinostat (suberoylanilide hydroxamic acid) in recurrent glioblastoma multiforme (GBM). [Abstract] J Clin Oncol 25 (Suppl 18): A-2004, 2007.

Responsible Party:	North Central Cancer Treatment Group ( Jan C. Buckner )
Study ID Numbers:	CDR0000445405, NCCTG-N047B
Study First Received:	October 12, 2005
Last Updated:	April 14, 2009
ClinicalTrials.gov Identifier:	NCT00238303 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

adult gliosarcoma
adult glioblastoma
recurrent adult brain tumor
adult giant cell glioblastoma

Study placed in the following topic categories:

Anticarcinogenic Agents
Anti-Inflammatory Agents
Glioblastoma
Astrocytoma
Vorinostat
Central Nervous System Neoplasms
Recurrence
Brain Neoplasms
Neuroectodermal Tumors
Analgesics, Non-Narcotic
Neoplasms, Germ Cell and Embryonal

Neuroepithelioma
Anti-Inflammatory Agents, Non-Steroidal
Peripheral Nervous System Agents
Analgesics
Glioma
Glioblastoma Multiforme
Antirheumatic Agents
Gliosarcoma
Nervous System Neoplasms
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Anticarcinogenic Agents
Anti-Inflammatory Agents
Glioblastoma
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Neoplasms, Nerve Tissue
Physiological Effects of Drugs
Central Nervous System Neoplasms
Neoplasms by Site
Sensory System Agents
Neoplasms, Germ Cell and Embryonal
Therapeutic Uses
Anti-Inflammatory Agents, Non-Steroidal
Glioma
Analgesics

Nervous System Neoplasms
Neoplasms by Histologic Type
Astrocytoma
Nervous System Diseases
Vorinostat
Enzyme Inhibitors
Protective Agents
Pharmacologic Actions
Neuroectodermal Tumors
Neoplasms
Analgesics, Non-Narcotic
Peripheral Nervous System Agents
Neoplasms, Neuroepithelial
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on September 11, 2009