Ropidoxuridine in Treating Patients With Advanced Gastrointestinal Cancer Undergoing Radiation Therapy

March 6, 2024 updated by: National Cancer Institute (NCI)

Phase I and Pharmacology Study of Oral 5-Iodo-2-Pyrimidinone-2'- Deoxyribose (IPdR) as a Prodrug for IUdR-Mediated Tumor Radiosensitization in Gastrointestinal Cancers

This phase I trial studies the side effects and best dose of ropidoxuridine in treating patients with gastrointestinal cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment undergoing radiation therapy. Ropidoxuridine may help radiation therapy work better by making tumor cells more sensitive to the radiation therapy.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. To conduct a phase I dose escalation trial, to determine the safety and the maximum tolerated dose (MTD), of oral (po) IPdR (ropidoxuridine) given daily for 28 consecutive days with concurrent intensity-modulated radiation therapy (IMRT) in patients with advanced gastrointestinal cancers treated with palliative radiation.

SECONDARY OBJECTIVES:

I. To observe and record anti-tumor activity. II. To establish the pharmacokinetics of daily po dosing of IPdR x 28 days. III. To assess, for patients treated at the MTD, for biochemical evidence of IPdR effect in normal tissue (circulating granulocytes) and tumor tissue (in patients with accessible tumor tissue) by measuring %iododeoxyuridine (IUdR)-deoxyribonucleic acid (DNA) cellular incorporation by flow cytometry and high-pressure liquid chromatography (HPLC) analyses.

IV. To assess the use of %IUdR-DNA cellular incorporation (measured by the investigational laboratory assays of flow cytometry and HPLC) as an exploratory biomarker of IPdR for the following effects: the %IUdR-DNA tumor cell incorporation from day 8 tumor biopsies in gastrointestinal (GI) cancer patients receiving MTD doses of IPdR as an exploratory biomarker of tumor radiosensitization using Response Evaluation Criteria in Solid Tumors (RECIST) criteria.

V. To assess the use of %IUdR-DNA cellular incorporation (measured by the investigational laboratory assays of flow cytometry and HPLC) as an exploratory biomarker of IPdR for the following effects: 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 complete blood count (CBC)/differential values.

OUTLINE: This is a dose-escalation study of ropidoxuridine.

Beginning 30 minutes to 2 hours before radiation therapy, patients receive ropidoxuridine PO once daily (QD) on days 1-28 in the absence of disease progression or unacceptable toxicity. Beginning on day 8, patients undergo IMRT 5 days a week for 3 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 4 weeks.

Study Type

Interventional

Enrollment (Actual)

19

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Rhode Island Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed advanced, incurable cancers of the esophagus, liver, stomach, small bowel, pancreas, bile duct, colon or rectum and be eligible to receive chest, abdominal and/or pelvic radiation therapy (RT) for palliation; documentation of this is required in physician note; concomitant systemic therapy is not allowed during administration of palliative RT; palliative RT can be considered for advanced primary tumors or metastatic disease as above
  • Patients must not have received systemic chemotherapy for at least 4 weeks, and must not have received prior radiation therapy to the tumor site being irradiated on this study
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • Life expectancy of greater than 12 weeks
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin within normal institutional limits
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
  • Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • 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
  • Human immunodeficiency virus (HIV) positive (+) patients with cluster of differentiation 4 (CD4) counts >= 250 cells/mm^3 on anti-viral therapy
  • Women of child-bearing potential must have a negative pregnancy test

Exclusion Criteria:

  • Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Patients who are receiving any other investigational agents
  • Patients with known brain metastases should be excluded from this clinical trial
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to IPdR
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (ropidoxuridine, IMRT)
Beginning 30 minutes to 2 hours before radiation therapy, patients receive ropidoxuridine PO QD on days 1-28 in the absence of disease progression or unacceptable toxicity. Beginning on day 8, patients undergo IMRT 5 days a week for 3 weeks in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Pharmacological Study
Correlative studies
Radiation: Intensity-Modulated Radiation Therapy
Undergo IMRT
Other Names:
  • IMRT
  • Intensity Modulated RT
  • Intensity-Modulated Radiotherapy
  • Radiation, Intensity-Modulated Radiotherapy
  • Intensity modulated radiation therapy (procedure)
Drug: Ropidoxuridine
Given PO
Other Names:
  • 5-Iodo-2-pyrimidinone 2' deoxyribonucleoside
  • 5-Iodo-2-pyrimidinone-2'-deoxyribose
  • IPdR

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Maximum tolerated dose (MTD) defined as the dose below which 2 or more of 6 patients experience dose-limiting toxicity
Time Frame: Up to 28 days
Up to 28 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
%iododeoxyuridine (IUdR)-deoxyribonucleic acid (DNA) incorporation in tumor biopsies
Time Frame: Up to 2 weeks
Correlate %IUdR-DNA incorporation in human gastrointestinal (GI) tumor biopsies in the proposed phase I and pharmacokinetic (PK) clinical trial in GI cancer patients receiving palliative abdominal and/or pelvic radiation therapy (RT) by linear regression.
Up to 2 weeks
Pharmacokinetic (PK) incorporation in tumor biopsies
Time Frame: Days 1, 15 and 22 before drug administration, at 30, 60, 120, and 240 minutes (and 24 hours on day 1 only) following drug administration
Correlate %IUdR-DNA incorporation in human GI tumor biopsies in the proposed phase I and PK clinical trial in GI cancer patients receiving palliative abdominal and/or pelvic RT by linear regression.
Days 1, 15 and 22 before drug administration, at 30, 60, 120, and 240 minutes (and 24 hours on day 1 only) following drug administration
%iododeoxyuridine (IUdR)-deoxyribonucleic acid (DNA) incorporation in peripheral (circulating) granulocytes
Time Frame: Up to 4 weeks after completion of study treatment
Correlate %IUdR-DNA incorporation in human GI tumor biopsies in the proposed phase I and PK clinical trial in GI cancer patients receiving palliative abdominal and/or pelvic RT by linear regression.
Up to 4 weeks after completion of study treatment
Pharmacokinetic (PK) incorporation in peripheral (circulating) granulocytes
Time Frame: Days 1, 15 and 22 before drug administration, 30, 60, 120, and 240 minutes (and 24 hours on day 1 only) following drug administration
Correlate %IUdR-DNA incorporation in human GI tumor biopsies in the proposed phase I and PK clinical trial in GI cancer patients receiving palliative abdominal and/or pelvic RT by linear regression.
Days 1, 15 and 22 before drug administration, 30, 60, 120, and 240 minutes (and 24 hours on day 1 only) following drug administration
Tumor response relationship to the %iododeoxyuridine (IUdR)-deoxyribonucleic acid (DNA) incorporation using Response Evaluation Criteria in Solid Tumors (RECIST) criteria based on high-pressure liquid chromatography (HPLC) and flow cytometry measurements
Time Frame: Day 8
Tumor response is the dependent variable and can be binomial (i.e. response versus [vs.] no response) or multinomial (i.e. complete response, partial response, stable disease or progressive disease) and the %IUdR-DNA incorporation is the independent variable.
Day 8

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Timothy J Kinsella, Rhode Island Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2016

Primary Completion (Actual)

November 8, 2018

Study Completion (Estimated)

March 5, 2025

Study Registration Dates

First Submitted

March 5, 2015

First Submitted That Met QC Criteria

March 5, 2015

First Posted (Estimated)

March 6, 2015

Study Record Updates

Last Update Posted (Actual)

March 7, 2024

Last Update Submitted That Met QC Criteria

March 6, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2015-00258 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • BRUOG 265
  • 9882 (Other Identifier: CTEP)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Stage III Pancreatic Cancer AJCC v6 and v7

Clinical Trials on Laboratory Biomarker Analysis

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Jordan

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe