An Early Phase I Study of IPdR Absorption, Metabolism, and Safety in Patients With Advanced Solid Tumors and Lymphomas
- 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
- 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.
-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.
- 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).
Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
-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.
Carl O Landgren, M.D.
National Cancer Institute (NCI)
United States: Federal Government
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Bethesda, Maryland 20892|