Hematopoietic and Lymphoid Cell NeoplasmPhase 1NCT02993146
Ropidoxuridine and Whole Brain Radiation Therapy in Treating Patients With Brain Metastases
A Phase 1 study testing Laboratory Biomarker Analysis, Pharmacological Study and Quality-of-Life Assessment in people with Hematopoietic and Lymphoid Cell Neoplasm and Malignant Solid Neoplasm, run by National Cancer Institute (NCI) at 14 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hematopoietic and Lymphoid Cell Neoplasm, Malignant Solid Neoplasm, Metastatic Malignant Neoplasm in the Brain
- What is being tested?
- Laboratory Biomarker Analysis, Pharmacological Study and Quality-of-Life Assessment
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 14 sitesUnited States
- Study dates
- 8 May 2017to 30 Sep 2027
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
- Ability to understand and the willingness to sign a written informed consent document
Who cannot join
- 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
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- 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
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
United States14 sites
University of Michigan Rogel Cancer Center
Ann Arbor, Michigan, 48109
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, 21201
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201
Weisberg Cancer Treatment Center
Farmington Hills, Michigan, 48334
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030
Ben Taub General Hospital
Houston, Texas, 77030
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242
UC San Diego Moores Cancer Center
La Jolla, California, 92093
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032
University of Nebraska Medical Center
Omaha, Nebraska, 68198
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112
About this study
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
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.
Read the detailed description
PRIMARY OBJECTIVE:
- 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:
- 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.
- 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:
- 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.
- Conditions
- Hematopoietic and Lymphoid Cell Neoplasm, Malignant Solid Neoplasm, Metastatic Malignant Neoplasm in the Brain
- Being tested
- Laboratory Biomarker Analysis, Pharmacological Study, Quality-of-Life Assessment, Ropidoxuridine, Whole-Brain Radiotherapy
- Medical subject headings
- Hematologic Neoplasms, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Laboratory Biomarker AnalysisOther
Correlative studies
Correlative studies
Quality-of-Life AssessmentOther
Also called Quality of Life Assessment
Ancillary studies
RopidoxuridineDrug
Also called 5-Iodo-2-pyrimidinone 2' deoxyribonucleoside, 5-Iodo-2-pyrimidinone-2'-deoxyribose, IPdR
Given PO
Whole-Brain RadiotherapyRadiation
Also called WBRT, whole-brain radiation therapy
Undergo WBRT
| Study group | Role | What they receive |
|---|---|---|
| Treatment (ropidoxuridine, WBRT) | Experimental | 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 in the absence of disease progression or unacceptable toxicity. Receives: Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Other: Quality-of-Life Assessment; Drug: Ropidoxuridine; Radiation: Whole-Brain Radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Experiencing a Dose Limiting Toxicity
Dose limiting toxicities are protocol-defined, treatment-related adverse events.
Measured: Up to week 8
Secondary outcomes (5)
Number of Participants With Complete Response, Partial Response, Stable Disease or Progressive Disease.
To observe and record anti-tumor activity as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Complete response is no remaining tumor. Partial response is a 30% or greater decrease in overall tumor burden. Progressive disease is a 20% or greater increase in tumor burden. Stable disease is between 20% increase and 30% decrease.
Measured: Up to 2 years
Intracranial Disease Status
Intracranial disease status assessed at month 6.
Measured: At 6 months
Pharmacokinetics of Oral IPdR
To establish the pharmacokinetics of daily oral dosing of IPdR for 8 days.
Measured: At Day 8
Number of Participants Experience Grade 3, 4, or 5 Adverse Events
To establish safety and tolerability of oral IPdR for 28 days with whole brain radiation treatment.
Measured: 28 days
Number of Participants With Delayed Neurological Toxicity
To estimate the incidence of delayed neurological toxicity at 2, 4, and 6 months after whole blood radiation treatment.
Measured: At 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2016 (estimated)
- Study start8 May 2017
- Primary completion19 Aug 2022
- Study completion30 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hematopoietic and Lymphoid Cell NeoplasmStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Pranshu Mohindra, Principal investigator, Mayo Clinic Cancer Center LAO
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02993146
- Sponsor's protocol ID
- NCI-2016-01909
- Other IDs
- NCI-2016-01909, HP-00067789, 9979, 9979, UM1CA186686, UM1CA186691
- Status last verified
- Sep 2026
- First submitted
- 14 Dec 2016
- Last updated
- 21 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No