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

• Status: Terminated
• Trial end date: 2009-04-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Collaborator: Schering-Plough
• Treatments: Dacarbazine; Histone Deacetylase Inhibitors; Temozolomide; Valproic Acid

Criteria

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.