An Early Phase I Study of IPdR Absorption, Metabolism, and Safety in Patients With Advanced Solid Tumors and Lymphomas
- 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.
- To evaluate the levels of drug and its breakdown products in the blood following a single dose of IPdR by mouth. .
- Individuals at least 18 years of age who have been diagnosed with cancer (solid tumors or lymphomas) that have not responded to standard treatment.
- 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.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||An Early Phase I Study of IPdR Absorption, Metabolism, and Safety in Patients With Advanced Solid Tumors and Lymphomas|
- -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.
|Study Start Date:||October 2010|
|Study Completion Date:||July 2012|
|Primary Completion Date:||July 2012 (Final data collection date for primary outcome measure)|
- 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.
- 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).
Please refer to this study by its ClinicalTrials.gov identifier: NCT01240577
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Shivaani Kummar, M.D.||National Cancer Institute (NCI)|