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Phase I Study of Temozolomide, Valproic Acid and Radiation Therapy in Patients With Brain Metastases

Primary Purpose

Brain Metastases

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Temozolomide

Valproic Acid

Whole Brain Radiation Therapy

About this trial

This is an interventional treatment trial for Brain Metastases focused on measuring histone deacetylase, unresectable brain metastases

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients must have cytologically/histologically documented solid tumor malignancies
Age > 18 years old
Patients must be candidates to receive WBR for unresectable brain metastases
Patients must have ECOG performance status 0-2
Patients must be able to give informed consent and able to follow guidelines given in the study
Neurologic Function Status 0,1, or 2
The patient has no major impairment of hematological function, as defined by the following laboratory parameters: WBC >3.0x10^9/L; ANC > 1.5 x 10^9/L; Hgb >9.0g/dL; PLT >100x10^9/L. Red blood cell transfusions and repeat evaluations for study entry are allowed
Patients must have adequate renal and normal hepatic function (creatinine < 1.5 x upper limit of normal (ULN), bilirubin and SGOT (AST), SGPT (ALT) within 1.5 x the upper institutional normal limits) obtained within 4 weeks prior to registration.
All patients of reproductive potential must use an effective method of contraception during the study and six months following termination of treatment. (Not applicable to patients with bilateral oophorectomy and/or hysterectomy or to female patients who are older than 50 years and have not had a menstrual cycle in more than one year).
Women of childbearing age must have a negative pregnancy test
Patients must have 10 mm or greater brain lesion on MRI scan performed within 4 weeks of enrollment

Exclusion Criteria:

Prior whole brain radiation
More than 1 active malignancy which may potentially cause brain metastasis
Patients on phenytoin, carbamazepine, phenobarbital, felbamate, meropenem, rifampin (Levetiracetam will be permitted)
Patients with active or any history of seizure disorders
Patients with uncontrolled nausea and vomiting
Chemotherapy, radiotherapy, or hormonal therapy within 2 weeks prior to entering the study or have not recovered from prior treatment-related toxicities (grade 2 or less)
Patients receiving any other investigational agents
Evidence of significant active infection (e.g., pneumonia, cellulitis, wound abscess, etc.) at time of study entry.
Leptomeningeal disease or hydrocephalous on MRI scan performed within 4 weeks of enrollment
Pregnant and breast feeding women are excluded from the study because effects on the fetus are unknown and there may be a risk of increased fetal wastage.

Sites / Locations

H. Lee Moffitt Cancer Center & Research Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Temazolomide, Valproic Acid and Radiation

Arm Description

Temazolomide, Valproic Acid and Whole Brain Radiation Therapy

Outcomes

Primary Outcome Measures

Safety and tolerability of temozolomide in combination with VPA and Whole-Brain Radiation

Determination of the MTD of VPA in combination with temozolomide and Whole-Brain Radiation

Secondary Outcome Measures

Response rate

Pharmacokinetics

Histone acetylation

Full Information

NCT ID

NCT00437957

First Posted

February 19, 2007

Last Updated

February 20, 2017

Sponsor

H. Lee Moffitt Cancer Center and Research Institute

Collaborators

Schering-Plough

1. Study Identification

Unique Protocol Identification Number

NCT00437957

Brief Title

Phase I Study of Temozolomide, Valproic Acid and Radiation Therapy in Patients With Brain Metastases

Official Title

Phase I Trial Of Temozolomide Combined With The Histone Deacetylase Inhibitor Valproic Acid (VPA) And Whole Brain Radiation Therapy (WBR) For Brain Metastases From Solid Tumors In Adults

Study Type

Interventional

2. Study Status

Record Verification Date

June 2011

Overall Recruitment Status

Terminated

Why Stopped

Lack of enrollment

Study Start Date

December 2006 (undefined)

Primary Completion Date

April 2009 (Actual)

Study Completion Date

April 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

H. Lee Moffitt Cancer Center and Research Institute

Collaborators

Schering-Plough

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

This type of study is called a "Phase I study". Its purpose is to determine the side effects of the two medicines listed in this study when given together with whole brain radiation, and the highest dose of valproic acid that can be given together with temozolomide and whole brain radiation. We will also study the drug combination's effectiveness in treating cancer. While both of these drugs and whole brain radiation have been used in people for many years, they have never been combined for the purpose of treating patients with cancer.

Detailed Description

At the start of the study, patients will be informed which dose level they will be treated with. On day 1, patients will have a physical exam and several blood draws including draws to measure the level of valproic acid in their body. Patients will start your whole brain radiation and also at the same time start the valproic acid and temozolomide pills. Patients will be asked to take the valproic acid pills every 12 hours and the temozolomide pills once daily. Patients will not need to come to the center for that but will need to come to the center to receive you whole brain radiation for 3 weeks (on weekdays, excluding holidays). Radiation therapy will not be administered on weekends but patients will still take their pills for the whole 3 weeks from starting the radiation. Patients will have to come back for a study visit weekly for the 6 months. Two more visits are also required: approximately 6 weeks and 10 weeks from starting the treatment. Patients will be asked about any old or new symptoms to determine if adjustment in the pill dose is required. Every study visit except the last one will include blood draws. These will evaluate blood counts, blood chemistry and also measure the level of valproic acid in your body. The Mini Mental Status examination described above will be repeated in every visit.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Brain Metastases

Keywords

histone deacetylase, unresectable brain metastases

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

10 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Temazolomide, Valproic Acid and Radiation

Arm Type

Experimental

Arm Description

Temazolomide, Valproic Acid and Whole Brain Radiation Therapy

Intervention Type

Drug

Intervention Name(s)

Temozolomide

Other Intervention Name(s)

Temodar

Intervention Description

75 Mg/m2/day for all Cohorts

Intervention Type

Drug

Intervention Name(s)

Valproic Acid

Other Intervention Name(s)

VPA

Intervention Description

Cohort 1: 20 mg/kg/day Cohort 2: 30 mg/kg/day Cohort 3: 40 mg/kg/day Cohort 4: 50 mg/kg/day

Intervention Type

Procedure

Intervention Name(s)

Whole Brain Radiation Therapy

Other Intervention Name(s)

WBRT

Intervention Description

Concurrently with Temozolomide and VPA

Primary Outcome Measure Information:

Title

Safety and tolerability of temozolomide in combination with VPA and Whole-Brain Radiation

Time Frame