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Trial record 36 of 211 for:    Oral Cancer | Recruiting Studies | NIH

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
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

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. Ropidoxuridine may help whole brain radiation therapy work better by making cancer cells more sensitive to the radiation therapy.

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

Detailed Description:

PRIMARY OBJECTIVES:

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.

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 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).

TERTIARY 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 %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)
Primary Purpose: Treatment
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

Arm Intervention/treatment
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
Correlative studies

Other: Pharmacological Study
Correlative studies

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Drug: Ropidoxuridine
Given PO
Other Names:
  • 5-Iodo-2-pyrimidinone 2' deoxyribonucleoside
  • 5-Iodo-2-pyrimidinone-2'-deoxyribose
  • IPdR

Radiation: Whole-Brain Radiotherapy
Undergo WBRT
Other Names:
  • WBRT
  • whole-brain radiation therapy




Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. 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).

  2. 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.

  3. Biomarkers [ Time Frame: Up to week 8 ]
    Biomarker data will be explored in a simple descriptive manner.

  4. 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.

  5. Overall survival [ Time Frame: Up to 2 years ]
    Will be explored using the Kaplan-Meier method.

  6. 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 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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; 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

Exclusion Criteria:

  • 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; breastfeeding should be discontinued if the mother is treated with IPdR

Information from the National Library of Medicine

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


Locations
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    burton@bcm.edu   
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    cancerinfo@hci.utah.edu   
Principal Investigator: Lindsay M. Burt         
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Pranshu Mohindra Mayo Clinic Cancer Center LAO

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02993146     History of Changes
Other Study ID Numbers: NCI-2016-01909
NCI-2016-01909 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
HP-00067789
9979 ( Other Identifier: Mayo Clinic Cancer Center LAO )
9979 ( Other Identifier: CTEP )
UM1CA186686 ( U.S. NIH Grant/Contract )
First Posted: December 15, 2016    Key Record Dates
Last Update Posted: December 11, 2018
Last Verified: November 2018

Additional relevant MeSH terms:
Neoplasms
Neoplasms, Second Primary
Brain Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases