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An Early Phase I Study of IPdR Absorption, Metabolism, and Safety in Patients With Advanced Solid Tumors and Lymphomas


Phase 1
18 Years
N/A
Not Enrolling
Both
Neoplasms, Lymphoma

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Trial Information

An Early Phase I Study of IPdR Absorption, Metabolism, and Safety in Patients With Advanced Solid Tumors and Lymphomas


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).

Inclusion Criteria


- INCLUSION CRITERIA:

- Patients must have histologically documented (confirmed at the Laboratory of
Pathology, NCI) solid tumors or lymphoid malignancies that are refractory to at least
one line of standard treatment or for which no standard therapy is available.
Patients with lymphoid malignancies may be enrolled if they have disease for which
standard therapy is currently not indicated. Patients should not have
disease-associated symptoms requiring immediate therapy or intervention.

- Any prior chemotherapy or radiation therapy must have been completed greater than or
equal to 2 weeks prior to enrollment (6 weeks for nitrosoureas or mitomycin C), and
the patient must have recovered to eligibility levels from prior toxicity.

- Age greater than or equal to 18 years. Patients under 18 years of age are excluded
because of their inability as a protected population to give appropriate consent to
this non-therapeutic study.

- ECOG performance status less than or equal to 2 (Karnofsky greater than or equal to
60%).

- Life expectancy of at least 3 months.

- Patients must have normal organ and marrow function as defined below:

- absolute neutrophil count greater than or equal to 1,500/microL

- platelets greater than or equal to 100,000/microL

- total bilirubin less than 1.5 times institutional upper limit of normal (ULN)

- AST(SGOT)/ALT(SGPT) less than or equal to 3.0 times ULN

- creatinine less than 1.5 times ULN

OR:

--creatinine clearance greater than or equal to 60 mL/min for patients with creatinine
levels greater than or equal to 1.5 times ULN

- IPdR is a nucleoside analog and therefore potentially teratogenic. 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 30 days
after study drug administration. Because there is an unknown but potential risk for
adverse events in nursing infants secondary to IPdR administration to the mother,
nursing mothers should not receive IPdR.

- Ability to understand and the willingness to sign a written informed consent
document.

EXCLUSION CRITERIA:

- Patients may not be receiving any other investigational agents.

- Uncontrolled intercurrent illness including, but not limited to, ongoing uncontrolled
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, GI conditions limiting absorption, serious skin conditions, or
psychiatric illness/social situations that would limit compliance with study
requirements.

- Women who are pregnant or nursing.

INCLUSION OF WOMEN AND MINORITIES:

-Both men and women and members of all races and ethnic groups are eligible for this
trial.

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

-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.

Principal Investigator

Carl O Landgren, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute (NCI)

Authority:

United States: Federal Government

Study ID:

110026

NCT ID:

NCT01240577

Start Date:

October 2010

Completion Date:

July 2012

Related Keywords:

  • Neoplasms
  • Lymphoma
  • IPdR
  • Pharmacokinetics
  • Early Phase I
  • Cancer
  • Solid Tumor
  • Lymphoma
  • Neoplasms
  • Lymphoma

Name

Location

National Institutes of Health Clinical Center, 9000 Rockville PikeBethesda, Maryland  20892