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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00437957
Recruitment Status : Terminated (Lack of enrollment)
First Posted : February 21, 2007
Last Update Posted : February 23, 2017
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute

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.

Condition or disease Intervention/treatment Phase
Brain Metastases Drug: Temozolomide Drug: Valproic Acid Procedure: Whole Brain Radiation Therapy Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : December 2006
Actual Primary Completion Date : April 2009
Actual Study Completion Date : April 2009

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Temazolomide, Valproic Acid and Radiation
Temazolomide, Valproic Acid and Whole Brain Radiation Therapy
Drug: Temozolomide
75 Mg/m2/day for all Cohorts
Other Name: Temodar

Drug: Valproic Acid
Cohort 1: 20 mg/kg/day Cohort 2: 30 mg/kg/day Cohort 3: 40 mg/kg/day Cohort 4: 50 mg/kg/day
Other Name: VPA

Procedure: Whole Brain Radiation Therapy
Concurrently with Temozolomide and VPA
Other Name: WBRT

Primary Outcome Measures :
  1. Safety and tolerability of temozolomide in combination with VPA and Whole-Brain Radiation [ Time Frame: approximately 74 days per patient ]
  2. Determination of the MTD of VPA in combination with temozolomide and Whole-Brain Radiation [ Time Frame: approximately 74 days per patient ]

Secondary Outcome Measures :
  1. Response rate [ Time Frame: approximately 74 days per patient ]
  2. Pharmacokinetics [ Time Frame: approximately 74 days per patient ]
  3. Histone acetylation [ Time Frame: approximately 74 days per patient ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00437957

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United States, Florida
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, United States, 33612
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
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Principal Investigator: Sajeel Chowdhary, MD H. Lee Moffitt Cancer Center and Research Institute
Principal Investigator: Jade Homsi, MD H. Lee Moffitt Cancer Center and Research Institute
Additional Information:
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Responsible Party: H. Lee Moffitt Cancer Center and Research Institute Identifier: NCT00437957    
Other Study ID Numbers: MCC-14886
105003A ( Other Identifier: USF IRB )
First Posted: February 21, 2007    Key Record Dates
Last Update Posted: February 23, 2017
Last Verified: June 2011
Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
histone deacetylase
unresectable brain metastases
Additional relevant MeSH terms:
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Neoplasm Metastasis
Neoplasms, Second Primary
Brain Neoplasms
Neoplastic Processes
Pathologic Processes
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Valproic Acid
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors
GABA Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs