Ropidoxuridine and Whole Brain Radiation Therapy in Treating Patients With Brain Metastases

Summary

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Description

PRIMARY OBJECTIVE: I. To conduct a phase 1 dose escalation trial in patients with brain metastases to determine the recommended phase -2 dose of ropidoxuridine (5-iodo-2-pyrimidinone-2'-deoxyribose [IPdR]) when administered alone orally once daily for 7 consecutive days and then concurrently with co...

PRIMARY OBJECTIVE: I. To conduct a phase 1 dose escalation trial in patients with brain metastases to determine the recommended phase -2 dose of ropidoxuridine (5-iodo-2-pyrimidinone-2'-deoxyribose [IPdR]) when administered alone orally once daily for 7 consecutive days and then concurrently with conventionally fractionated whole brain radiation therapy (WBRT) for additional 21 days. SECONDARY OBJECTIVES: I. To observe and record anti-tumor activity to IPdR-mediated radiosensitization. II. To estimate 6 month intracranial progression-free survival (PFS) in brain metastasis cancer patients who receive daily oral IPdR x 28 days and WBRT. III. To establish the pharmacokinetics of daily oral dosing of IPdR times 8 days. IV. To evaluate safety and tolerability of oral IPdR x 28 days and WBRT. V. To estimate the incidence of delayed neurological toxicity at 2, 4, and 6 months (+/-1 week) post-completion of WBRT (for patients without intracranial progression) including: Va. Delayed-recall through Hopkins Verbal Learning Test Revised (HVLT-R). Vb. Quality of life as measured by the Functional Assessment of Cancer Therapy-Brain (FACT-BR). CORRELATIVE OBJECTIVES: I. To assess for biochemical evidence of IPdR effect in normal tissues (circulating granulocytes) by measuring %IUdR-deoxyribonucleic acid (DNA) cellular incorporation by flow cytometry and high-pressure liquid chromatography (HPLC) analyses as an exploratory biomarker for the following: Ia. %IUdR-DNA tumor cell incorporation from day 8 extracranial tumor biopsies in brain metastasis cancer patients receiving RP2D doses of IPdR as an exploratory biomarker of tumor radiosensitization using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Ib. %IUdR-DNA cellular incorporation in patients' circulating granulocytes taken weekly during the 28-day IPdR RP2D dose, on day 29, and week 8 as an exploratory biomarker of IPdR systemic toxicities to bone marrow as measured by serial complete blood count (CBC)/differential values. OUTLINE: This is a dose escalation study of ropidoxuridine. Patients receive ropidoxuridine orally (PO) once daily (QD) on days 1-28 and undergo WBRT daily for not more than 5 days per week beginning on day 8 for a total of 15 fractions in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 2 months for 6 months, every 3-4 months for 6 months, and every 6 months for 1 year.

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