Ropidoxuridine and Whole Brain Radiation Therapy in Treating Patients With Brain Metastases
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
5 other identifiers
interventional
11
1 country
14
Brief Summary
This phase I trial studies the side effects and best dose of ropidoxuridine when given together with whole brain radiation therapy in treating patients with cancer that has spread to the brain (brain metastases). Ropidoxuridine may help whole brain radiation therapy work better by making cancer cells more sensitive to the radiation therapy.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started May 2017
Longer than P75 for phase_1
14 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 14, 2016
CompletedFirst Posted
Study publicly available on registry
December 15, 2016
CompletedStudy Start
First participant enrolled
May 8, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 19, 2022
CompletedResults Posted
Study results publicly available
February 20, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
October 3, 2026
ExpectedApril 30, 2026
March 1, 2026
5.3 years
December 14, 2016
October 17, 2023
April 9, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Number of Participants Experiencing a Dose Limiting Toxicity
Dose limiting toxicities are protocol-defined, treatment-related adverse events.
Up to week 8
Secondary Outcomes (5)
Number of Participants With Complete Response, Partial Response, Stable Disease or Progressive Disease.
Up to 2 years
Intracranial Disease Status
At 6 months
Pharmacokinetics of Oral IPdR
At Day 8
Number of Participants Experience Grade 3, 4, or 5 Adverse Events
28 days
Number of Participants With Delayed Neurological Toxicity
At 6 months
Study Arms (1)
Treatment (ropidoxuridine, WBRT)
EXPERIMENTALPatients 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 in the absence of disease progression or unacceptable toxicity.
Interventions
Ancillary studies
Given PO
Undergo WBRT
Eligibility Criteria
You may qualify if:
- Patients must have histologically confirmed malignancy with brain metastases and are being recommended palliative WBRT
- Life expectancy of greater than 2 months to allow completion of study treatment and assessment of dose-limiting toxicity
- Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
- Leukocytes \>= 3,000/mcL
- Absolute neutrophil count \>= 1,000/mcL
- Platelets \>= 100,000/mcL
- Calculated creatinine clearance \>= 45 mL/min/1.73 m\^2
- Total bilirubin:
- If no known liver metastases: total bilirubin \< 1.5 x institutional upper limit of normal (ULN)
- If known liver metastases, then: total bilirubin \< 2.5 x ULN
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]):
- If no known liver metastases: AST/SGOT and ALT/SGPT both \< 2 x ULN
- If known liver metastases, then: AST/SGOT and ALT/SGPT both \< 5 x ULN
- Human immunodeficiency virus (HIV) positive (+) patients with CD4 counts \>= 250 cells/mm\^3 on anti-viral therapy are eligible for the study
- Negative urine or serum pregnancy test result for females of child bearing potential only; Note: The effects of IPdR on the developing human fetus are unknown; for this reason and because radiation therapy is known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men and women treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of IPdR administration
- +1 more criteria
You may not qualify if:
- Presence of diffuse lepto or pachy meningeal carcinomatosis (focal/localized involvement from limited meningeal based metastases acceptable), greater than 1 cm mid-line shift, uncal herniation, or severe hemorrhage/hydrocephalous (small intra-lesional hemorrhage or anticipated surgical cavity is acceptable); patients with seizure at presentation who have been started on levetiracetam and have been stable for 48 hours prior to study registration are eligible at the discretion of treating physician
- Patients who have received systemic cytotoxic chemotherapy or approved oral targeted therapy or immunotherapy for 2 weeks, or other investigational agents for 3 weeks (4 half-lives for any oral targeted agents), or radiotherapy to a non-brain site for 2 weeks before initiation of IPdR therapy; patients who have recovered from serious (Common Terminology Criteria for Adverse Events \[CTCAE\] grade 3 or more higher) to grade 1 or less adverse events from the previous therapies are eligible; prior/current/future hormonal therapy and/or bisphosphonates are permitted with no minimum interval to initiation of study therapy; if indicated, patients can receive palliative radiation therapy to a non-brain site concurrent or immediately post-study treatment with no minimum interval to initiation of study therapy
- Patients must not have received prior whole brain radiation therapy; previous SRS/SRT done at least 3 weeks from the planned start of IPdR therapy is acceptable; SRS/SRT/fractionated boosts or neurosurgery can be performed once the dose limiting toxicity (DLT) assessment has been completed, if felt clinically necessary
- Patients with primary tumors including germ cell tumor, or lymphoma/leukemia
- Patients who are receiving any other investigational agent
- Patients needing more than 8 mg dexamethasone per day at the time of start of WBRT will not be eligible to participate in the study; however, patients will be allowed entry into the study if it is medically safe to reduce the daily dose of dexamethasone to 8 mg or less from the day of the start of WBRT; the dexamethasone dose for such patients may be increased beyond 8 mg per day during the course of treatment if medically necessary; this increased need for dose should be communicated to the study's principal investigator, Dr Mohindra at the University of Maryland
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to IPdR
- Uncontrolled intercurrent illness if it would increase the risk of toxicity or limit compliance with study requirements; this includes, but is not limited to, ongoing uncontrolled serious infection requiring intravenous (i.v.) antibiotics, progressive congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant women are excluded from this study because IPdR is an agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with IPdR, breastfeeding should be discontinued if the mother is treated with IPdR
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (14)
UC San Diego Moores Cancer Center
La Jolla, California, 92093, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242, United States
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, 21201, United States
University of Michigan Rogel Cancer Center
Ann Arbor, Michigan, 48109, United States
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201, United States
Weisberg Cancer Treatment Center
Farmington Hills, Michigan, 48334, United States
University of Nebraska Medical Center
Omaha, Nebraska, 68198, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111, United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030, United States
Ben Taub General Hospital
Houston, Texas, 77030, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Grants Administrative Manager
- Organization
- Johns Hopkins University
Study Officials
- PRINCIPAL INVESTIGATOR
Pranshu Mohindra
Mayo Clinic Cancer Center LAO
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 14, 2016
First Posted
December 15, 2016
Study Start
May 8, 2017
Primary Completion
August 19, 2022
Study Completion (Estimated)
October 3, 2026
Last Updated
April 30, 2026
Results First Posted
February 20, 2024
Record last verified: 2026-03