Ropidoxuridine and Whole Brain Radiation Therapy in Treating Patients With Brain Metastases
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|ClinicalTrials.gov Identifier: NCT02993146|
Recruitment Status : Recruiting
First Posted : December 15, 2016
Last Update Posted : December 11, 2018
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Malignant Neoplasm Metastatic Malignant Neoplasm in the Brain||Other: Laboratory Biomarker Analysis Other: Pharmacological Study Other: Quality-of-Life Assessment Drug: Ropidoxuridine Radiation: Whole-Brain Radiotherapy||Phase 1|
I. To conduct a phase 1 dose escalation trial in patients with brain metastases to determine the maximum tolerated dose (MTD) 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.
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 delayed-recall through Hopkins Verbal Learning Test Revised (HVLT-R) and quality of life as measured by the Functional Assessment of Cancer Therapy-Brain (FACT-BR).
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 %IUdR-DNA tumor cell incorporation from day 8 extracranial tumor biopsies in brain metastasis cancer patients receiving MTD doses of IPdR as an exploratory biomarker of tumor radiosensitization using Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
II. 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 %IUdR-DNA cellular incorporation in patients' circulating granulocytes taken weekly during the 28-day IPdR MTD 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.
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||47 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase 1 and Pharmacology Study of Oral 5-Iodo-2-Pyrimidinone-2-Deoxyribose (IPdR) as a Prodrug for IUdR-Mediated Tumor Radiosensitization in Brain Metastases|
|Actual Study Start Date :||December 7, 2016|
|Estimated Primary Completion Date :||August 1, 2019|
|Estimated Study Completion Date :||August 1, 2019|
Experimental: Treatment (ropidoxuridine, WBRT)
Patients receive ropidoxuridine PO 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.
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
Other: Quality-of-Life Assessment
Other Name: Quality of Life Assessment
Radiation: Whole-Brain Radiotherapy
- Maximum tolerated dose of ropidoxuridine defined as defined as the highest dose that has fewer than 3 (out of 6) patients experiencing dose-limiting toxicity assessed by National Cancer Institute's Common Toxicity Criteria version 4 [ Time Frame: Up to week 8 ]
- Tumor response assessed by Response Evaluation Criteria in Solid Tumors 1.1 [ Time Frame: Up to 2 years ]Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease in this patient population (overall and by tumor group).
- Pharmacokinetic parameters of daily oral dosing of ropidoxuridine [ Time Frame: Pre-dose, 30, 60, 120, 240 minutes and 24 hours following oral dose administration on day 1 of course 1; pre-dose, 30, 60, 120, and 240 minutes following oral dose administration on days 15 and 22 of course 1 ]The pharmacokinetics of daily oral dosing of ropidoxuridine for 28 days will be explored.
- Biomarkers [ Time Frame: Up to week 8 ]Biomarker data will be explored in a simple descriptive manner.
- Intracranial progression free survival (icPFS) [ Time Frame: From the date of start of treatment to time of progression or death, whichever occurs first, assessed at 6 months ]This will be explored using the Kaplan-Meier method. The icPFS estimates at 6 months with their standard error of the estimate will be reported.
- Overall survival [ Time Frame: Up to 2 years ]Will be explored using the Kaplan-Meier method.
- Incidence of delayed neurological toxicity including delayed-recall assessed by Hopkins Verbal Learning Test Revised (HVLT-R) and quality of life assessed by Functional Assessment of Cancer Therapy-Brain (FACT-BR) [ Time Frame: Up to 6 months ]
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 ClinicalTrials.gov identifier (NCT number): NCT02993146
|United States, California|
|UC San Diego Moores Cancer Center||Active, not recruiting|
|La Jolla, California, United States, 92093|
|University of California Davis Comprehensive Cancer Center||Recruiting|
|Sacramento, California, United States, 95817|
|Contact: Site Public Contact 916-734-3089|
|Principal Investigator: Karen L. Kelly|
|United States, Iowa|
|University of Iowa/Holden Comprehensive Cancer Center||Recruiting|
|Iowa City, Iowa, United States, 52242|
|Contact: Site Public Contact 800-237-1225|
|Principal Investigator: Mohammed M. Milhem|
|United States, Maryland|
|University of Maryland/Greenebaum Cancer Center||Recruiting|
|Baltimore, Maryland, United States, 21201|
|Contact: Site Public Contact 800-888-8823|
|Principal Investigator: Pranshu Mohindra|
|United States, Michigan|
|University of Michigan Comprehensive Cancer Center||Recruiting|
|Ann Arbor, Michigan, United States, 48109|
|Contact: Site Public Contact 800-865-1125|
|Principal Investigator: Michelle M. Kim|
|United States, New York|
|Columbia University/Herbert Irving Cancer Center||Active, not recruiting|
|New York, New York, United States, 10032|
|United States, Pennsylvania|
|Fox Chase Cancer Center||Recruiting|
|Philadelphia, Pennsylvania, United States, 19111|
|Contact: Site Public Contact 215-728-4790|
|Principal Investigator: Stephanie E. Weiss|
|United States, Texas|
|Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Site Public Contact 713-798-1354 firstname.lastname@example.org|
|Principal Investigator: Jacob Mandel|
|Ben Taub General Hospital||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Site Public Contact 713-873-2000|
|Principal Investigator: Jacob Mandel|
|United States, Utah|
|Huntsman Cancer Institute/University of Utah||Recruiting|
|Salt Lake City, Utah, United States, 84112|
|Contact: Site Public Contact 888-424-2100 email@example.com|
|Principal Investigator: Lindsay M. Burt|
|Principal Investigator:||Pranshu Mohindra||Mayo Clinic Cancer Center LAO|