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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

Phase 1
18 Years
Not Enrolling
Brain Metastases

Thank you

Trial Information

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

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

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.

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 >3.0x109/L; ANC > 1.5 x 109/L; Hgb >9.0g/dL; PLT
>100x109/L. Red blood cell transfusions and repeat evaluations for study entry are

- 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

- 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.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Time Frame:

approximately 74 days per patient

Safety Issue:


Principal Investigator

Sajeel Chowdhary, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

H. Lee Moffitt Cancer Center and Research Institute


United States: Institutional Review Board

Study ID:




Start Date:

December 2006

Completion Date:

April 2009

Related Keywords:

  • Brain Metastases
  • histone deacetylase
  • unresectable brain metastases
  • Neoplasm Metastasis
  • Neoplasms, Second Primary
  • Brain Neoplasms



H. Lee Moffitt Cancer Center & Research Institute Tampa, Florida  33612