Magnetic Resonance Spectroscopy Imaging in Predicting Response to Vorinostat and Temozolomide in Patients With Recurrent or Progressive Glioblastoma

NCT ID: NCT01342757

Last Updated: 2018-01-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-12-31
• Study Completion Date: 2012-05-31

Brief Summary

This clinical trial is studying magnetic resonance spectroscopy imaging in predicting response in patients to vorinostat and temozolomide in patients with recurrent, progressive, or newly diagnosed glioblastoma. 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. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Vorinostat may also help temozolomide work better by making tumor cells more sensitive to the drug. Imaging procedures, such as magnetic resonance spectroscopy imaging, may help measure the patient's response to vorinostat and temozolomide and allow doctors to plan better treatment.

Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate the strength of the association between magnetic resonance spectroscopy (MRS) imaging measurable biomarkers and response to vorinostat plus temozolomide.

SECONDARY OBJECTIVES:

I. To evaluate MRS-detected inositol and N-acetylaspartate (NAA) levels (at 3 tesla) as indicators of mood alterations as measured by a self-report depression survey (IDS-SR).

OUTLINE:

Patients receive vorinostat orally (PO) once daily (QD) on days -7 to -1 (course 1 only) and days 8-14 and 22-28 and temozolomide PO QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients previously treated with standard radiotherapy and temozolomide receive maintenance temozolomide PO on days 1-5.

Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicities. Patients undergo magnetic resonance spectroscopy imaging at baseline and at approximately 1 and 8 weeks on treatment. Patients also undergo an Inventory of Depression Symptomatology Self-Reported (IDS-SR) assessment at baseline and periodically during study.

Conditions

Adult Glioblastoma; Depression; Recurrent Adult Brain Tumor

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Arm I

Patients receive vorinostat once daily on days -7 to -1 (course 1 only) and days 8-14 and 22-28 and temozolomide on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients undergo magnetic resonance spectroscopic imaging at baseline and at approximately 1 and 8 weeks on treatment. Patients also undergo a survey administration of Inventory of Depression Symptomatology Self-Reported (IDS-SR) assessment at baseline and periodically during study.

Group Type: EXPERIMENTAL

vorinostat

Intervention Type: DRUG

Given orally

temozolomide

Intervention Type: DRUG

Given orally

magnetic resonance spectroscopic imaging

Intervention Type: PROCEDURE

Undergo MRI

survey administration

Intervention Type: OTHER

Ancillary studies

Interventions

vorinostat

Given orally

Intervention Type: DRUG

temozolomide

Given orally

Intervention Type: DRUG

magnetic resonance spectroscopic imaging

Undergo MRI

Intervention Type: PROCEDURE

survey administration

Ancillary studies

Intervention Type: OTHER

Other Intervention Names

L-001079038; SAHA; suberoylanilide hydroxamic acid; Zolinza; SCH 52365; Temodal; Temodar; TMZ; 1H-nuclear magnetic resonance spectroscopic imaging; Proton Magnetic Resonance Spectroscopic Imaging

Eligibility Criteria

Inclusion Criteria

• Patients must have 1 of the following:

• Diagnosis of recurrent or progressive glioblastoma

• Patients with recurrent disease may have had treatment for any number of prior relapses
• Newly diagnosed glioblastoma and have completed radiation therapy and are receiving standard follow-up temozolomide
• Must be able to have an MRI, and have a measurable contrast-enhancing supratentorial tumor of at least 1 cm by shortest diameter
• Residual disease following resection measuring 1 cm in diameter or greater is mandated for eligibility into the study
• Patients must have a stable or progressive disease as determined by serial brain MRI using the McDonald Criteria on a scan 14 days or fewer before registration and on a stable steroid dose for 5 days
• Patients with prior therapy that included interstitial brachytherapy or stereotactic radiosurgery must have confirmation of true progressive disease rather than radiation necrosis based upon either positron emission tomography (PET) or thallium scanning, MR spectroscopy, or surgical documentation of disease
• White Blood Cell Count > 3,000/μL
• Absolute Neutrophil Count > 1,500/μL
• Platelet count > 100,000/μL
• Hemoglobin > 10 g/dL (transfusion allowed)
• Serum glutamate oxaloacetate transaminase < 2 times upper limit of normal (ULN)
• Bilirubin < 2 times ULN
• Creatinine < 1.5 mg/dL
• Negative pregnancy test
• Women of childbearing potential and men must agree to use adequate barrier contraception for the duration of study participation
• Able to swallow capsules
• No patients with pacemakers, non-titanium aneurysm clips, neurostimulators, cochlear implants, non-titanium metal in ocular structures, history of being a steel worker, or other incompatible implants
• No significant medical illnesses that, in the investigator's opinion, cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy
• No history of any other cancer except non-melanoma skin cancer or carcinoma in-situ of the cervix, or cancer in complete remission and off all therapy for ≥ 3 years
• No active infection or serious intercurrent medical illness
• No disease that would obscure toxicity or dangerously alter drug metabolism
• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat (SAHA) or other agents used in this study
• No prolonged corrected QT interval waves on baseline EKG
• No other anticancer therapy (including chemotherapy, radiation, hormonal treatment, or immunotherapy) of any kind is permitted during the study period
• At least 3 weeks since prior radiotherapy
• Patients must have recovered from the toxic effects of prior therapy, including surgery
• At least 28 days since any prior investigational agent or prior cytotoxic therapy
• At least 23 days since prior temozolomide
• At least 14 days since prior vincristine (42 days for nitrosourea)
• At least 21 days since prior procarbazine
• At least 7 days since prior non-cytotoxic agents (e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, etc.)
• At least 2 weeks since prior valproic acid (or another histone deacetylase inhibitor)
• No other concurrent investigational agents

Exclusion Criteria

• Diagnostic and Statistical Manual-IV Axis I or II diagnosis (as determined by PI), exclusive of nicotine dependence.
• Pregnant.
• Contraindications to MRI: pacemaker, aneurysm clips, neurostimulators, cochlear implants, metal in eyes, steel worker, or other implants.
• Active medical or neurological disorder.
• History of alcohol or drug dependence

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jeffrey Olson

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Emory University

Atlanta, Georgia, United States

Countries

United States

References

Shim H, Wei L, Holder CA, Guo Y, Hu XP, Miller AH, Olson JJ. Use of high-resolution volumetric MR spectroscopic imaging in assessing treatment response of glioblastoma to an HDAC inhibitor. AJR Am J Roentgenol. 2014 Aug;203(2):W158-65. doi: 10.2214/AJR.14.12518.

Reference Type: RESULT

PMID: 25055291 (View on PubMed)

Other Identifiers

EMORY IRB #00044064

Identifier Type: OTHER

Identifier Source: secondary_id

WCI-44064

Identifier Type: OTHER

Identifier Source: secondary_id

R21CA141836

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2011-02569

Identifier Type: -

Identifier Source: org_study_id