An Early Phase I Study of IPdR Absorption, Metabolism, and Safety in Patients With Advanced Solid Tumors and Lymphomas
Condition: Neoplasms; Lymphoma
MeSH terms: Lymphoma
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

      - The experimental drug IPdR is broken down in the body to IdUrd, which has been given to
      patients to find out if it can improve radiation therapy. IdUrd has to be given through a
      vein; therefore this new drug (IPdR) has been made which can be taken by mouth. Researchers
      are interested in determining whether IPdR should also be studied to find out if it can
      improve radiation therapy. The current study is to find out if people absorb the drug given
      by mouth.

      Objectives:

      - To evaluate the levels of drug and its breakdown products in the blood following a single
      dose of IPdR by mouth. .

      Eligibility:

      - Individuals at least 18 years of age who have been diagnosed with cancer (solid tumors or
      lymphomas) that have not responded to standard treatment.

      Design:

        -  This study involves an initial dosing visit, one day of admission to the hospital for
           blood work, and a follow-up visit 14 days later.

        -  Participants will be screened with a physical examination and medical history, as well
           as blood and urine samples.

        -  Participants will receive a single dose of IPdR, and will provide multiple blood and
           urine samples for 24 hours after administration of the drug.

        -  Fourteen days after receiving IPdR, participants will have another physical examination
           and additional blood and urine tests to evaluate how IPdR has been broken down by the
           body.

        -  Cancer treatment will not be provided as part of this protocol.
    

Detailed description: 
      Background:

        -  The nucleoside analog iododeoxyuridine (IdUrd, NSC 39661) has shown promising activity
           as a radiosensitizer in preclinical models and has been evaluated in Phase I/II clinical
           trials. The extent of radiosensitization is directly related to the incorporation of
           IdUrd into tumor DNA as a replacement for thymidine.

        -  IPdR (NSC 726188) is an orally administered prodrug of IdUrd with a better therapeutic
           index in preclinical models.

        -  This first in human study of IPdR will evaluate whether IPdR is absorbed and what plasma
           levels of IPdR and its major metabolite, IdUrd, are achieved after a single oral dose.

      Objectives:

        -  Measure plasma concentrations of IPdR, IdUrd, and IdUrd metabolites after a single oral
           dose of IPdR

        -  Determine the safety of administering a single oral dose of IPdR.

      Eligibility:

      -Patients must be greater than or equal to 18 years of age and have histologically confirmed
      solid tumors or lymphoid malignancies refractory to at least one line of standard treatment
      or for which no standard therapy is available. Patients should have adequate organ function
      and no disease-associated symptoms requiring immediate therapy or intervention.

      Study Design:

        -  Patients will receive a single oral dose of IPdR on day 1.

        -  The initial IPdR dose will be 150 mg; dose escalation will be in 100% increments to a
           maximum of 2400 mg. One patient will be accrued to each dose level until we reach the
           highest dose level. Six patients will be accrued at dose level 5 (2400 mg).
    

Intervention name(s): IPdR
Intervention type(s): Drug
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: IPdR; Pharmacokinetics; Early Phase I; Cancer; Solid Tumor; Lymphoma