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

NCT00437957 | Terminated Phase 1

• 2 other identifiers: MCC-14886105003A
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Brain Metastases

Keywords

histone deacetylase; unresectable brain metastases

Outcome Measures

Primary Outcomes (2)

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

  approximately 74 days per patient

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

  approximately 74 days per patient

Secondary Outcomes (3)

• Response rate

  approximately 74 days per patient

• Pharmacokinetics

  approximately 74 days per patient

• Histone acetylation

  approximately 74 days per patient

Study Arms (1)

Temazolomide, Valproic Acid and Radiation

EXPERIMENTAL

Temazolomide, Valproic Acid and Whole Brain Radiation Therapy

Drug: Temozolomide; Drug: Valproic Acid; Procedure: Whole Brain Radiation Therapy

Interventions

Temozolomide DRUG

75 Mg/m2/day for all Cohorts

Also known as: Temodar

Temazolomide, Valproic Acid and Radiation

Valproic Acid DRUG

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

Also known as: VPA

Temazolomide, Valproic Acid and Radiation

Whole Brain Radiation Therapy PROCEDURE

Concurrently with Temozolomide and VPA

Also known as: WBRT

Temazolomide, Valproic Acid and Radiation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Schering-Plough: collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

Location

MeSH Terms

Conditions

Brain Neoplasms

Interventions

Temozolomide; Valproic Acid

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pentanoic Acids; Valerates; Acids, Acyclic; Carboxylic Acids; Fatty Acids, Volatile; Fatty Acids; Lipids

Study Officials

• Sajeel Chowdhary, MD

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

• Jade Homsi, MD

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 19, 2007
• First Posted: February 21, 2007
• Study Start: December 1, 2006
• Primary Completion: April 1, 2009
• Study Completion: April 1, 2009
• Last Updated: February 23, 2017

Record last verified: 2011-06

Locations

US (1)