Completed

A Phase I Study of Triapine® in Combination With Irinotecan in Refractory Tumors

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What is being tested

triapine

+ irinotecan hydrochloride
+ laboratory biomarker analysis
Drug
Other
Who is being recruted

Over 18 Years
See all eligibility criteria
How is the trial designed

Treatment Study

Phase 1
Interventional
Study Start: March 2004
See protocol details

Summary

Principal SponsorNational Cancer Institute (NCI)
Last updated: January 14, 2026
Sourced from a government-validated database.Claim as a partner
Study start date: March 1, 2004Actual date on which the first participant was enrolled.

PRIMARY OBJECTIVES: I. To find the maximal tolerated dose for the combination of irinotecan and Triapine® in patients with refractory solid tumors. SECONDARY OBJECTIVES: I. To find the severity and frequency of toxicity associated with this combination and to observe for and record any antitumor activity. TERTIARY OBJECTIVES: I. To evaluate the effect of Triapine®/irinotecan on the ribonucleotide reductase tyrosyl radical in vivo by Electron Paramagnetic Spectroscopy (EPR) in buccal mucosal cells, peripheral blood lymphocytes and in tumor biopsies. Formation of low molecular weight iron-Triapine® chelates will also be assessed by EPR. II. To evaluate the effect of Triapine® /irinotecan on cell cycle in vivo by measuring S-phase arrest in buccal mucosal cells. III. To evaluate the effect of Triapine® /irinotecan on MDR gene expression and polymorphisms in blood. IV. To evaluate the effect of Triapine® /irinotecan on ribonucleotide reductase R2 mRNA and Immunohistochemistry. V. To evaluate the pharmacokinetic profile of the combination. OUTLINE: This is a dose-escalation study. Patients receive irinotecan IV over 1 hour on day 1 and 3-AP (Triapine®) IV over 2 hours on days 1-3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of irinotecan and 3-AP (Triapine®) until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 6 additional patients are treated at that dose. Patients are followed until disease progression.

Official TitleA Phase I Study of Triapine® in Combination With Irinotecan in Refractory Tumors 
NCT00084877
Principal SponsorNational Cancer Institute (NCI)
Last updated: January 14, 2026
Sourced from a government-validated database.Claim as a partner

Protocol

This section provides details of the study plan, including how the study is designed and what the study is measuring.
Design Details
36 patients to be enrolledTotal number of participants that the clinical trial aims to recruit.
Treatment Study
These studies test new ways to treat a disease, condition, or health issue. The goal is to see if a new drug, therapy, or approach works better or has fewer side effects than existing options.

How participants are assigned to different groups/arms
In this clinical study, all participants receive the same treatment. Since there is only one group, there is no need for randomization or assignment to different arms. This type of study is often used to test a new treatment without comparing it to another.

Other Ways to Assign Participants
Randomized allocation
: Participants are assigned randomly, like flipping a coin, to ensure fairness and reduce bias.

Non-randomized allocation
: Participants are assigned based on specific factors, such as their medical condition or a doctor's decision.

How treatments are given to participants
In this study, all participants receive the same treatment. This approach is often used to evaluate the effects of a single intervention without comparing it to another.

Other Ways to Assign Treatments
Parallel assignment
: Participants are split into separate groups, each receiving a different treatment.

Cross-over assignment
: Participants switch between treatments during the study.

Factorial assignment
: Participants receive different combinations of treatments.

Sequential assignment
: Participants receive treatments one after another in a specific order, possibly based on individual responses.

Other assignment
: Treatment assignment does not follow a standard or predefined design.

How the effectiveness of the treatment is controlled
In a non placebo-controlled study, no participants receive an inert substance (placebo) to compare outcomes. Instead, all participants receive either the experimental treatment or an alternative treatment (often the Standard of Care). This method allows researchers to compare the effects of the experimental treatment with those of a different active intervention, rather than a placebo.

Other Options
Placebo-Controlled
: A placebo is used to compare the effects of the experimental treatment with those of an inert substance, isolating the true treatment effect.

How the interventions assigned to participants is kept confidential
Everyone involved in the study knows which treatment is being given. This is typically used when it's not possible or necessary to hide the treatment details from participants or researchers.

Other Ways to Mask Information
Single-blind
: Participants do not know which treatment they are receiving, but researchers do.

Double-blind
: Neither participants nor researchers know which treatment is given.

Triple-blind
: Participants, researchers, and outcome assessors do not know which treatment is given.

Quadruple-blind
: Participants, researchers, outcome assessors, and care providers all do not know which treatment is given.

Eligibility

Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.
Criteria
Any sexBiological sex of participants that are eligible to enroll.
Over 18 YearsRange of ages for which participants are eligible to join.
Healthy volunteers not allowedIf individuals who are healthy and do not have the condition being studied can participate.
Criteria

Inclusion Criteria: * Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative chemotherapy measures do not exist or are no longer effective * Patients must not have previously received irinotecan * Patients must not have received radiation to \> 25% of bone marrow * ECOG performance status =\< 2 * Life expectancy of greater than 12 weeks * Leukocytes \>= 3,000/μl * Absolute neutrophil count \>= 1,500/μl * Platelets \>= 100,000/μl * Total bilirubin within normal institutional limits * AST(SGOT)/ALT(SGPT) =\< 2.5 X institutional upper limit of normal * Creatinine =\< 1.5 mg/dl OR creatinine clearance \>= 50 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal * Patients must have measurable or evaluable disease * Patients must have baseline screening for G6PD (glucose-6-phosphate dehydrogenase) deficiency; G6PD must be no lower than the lower limit of normal prior to starting study treatment; patients who are above the upper limit of normal may enroll in the trial * The effects of Triapine® on the developing human fetus are unknown; for this reason and because heterocyclic carboxaldehyde thiosemicarbazones as well as other therapeutic agents used in this trial are known to be 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 the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately * Ability to understand and the willingness to sign a written informed consent document * Patients must have a baseline screening test for UGT1A1; the UGT1A1 cannot be the 7/7 genotype; patients who have any other combinations (6/6, 6/7, 5/7, etc.) may enroll in the trial Exclusion Criteria: * Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study * Patients who have not recovered from adverse events due to agents administered more than 4 weeks earlier; patients with grade 1 adverse events from prior therapies are eligible at the investigator's discretion * Patients may not be receiving any other investigational agents * History of allergic reactions attributed to compounds of similar chemical or biologic composition to Triapine® or other agents used in study * 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 because Triapine® is a heterocyclic carboxaldehyde thiosemicarbazone with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Triapine®, breastfeeding should be discontinued if the mother is treated with Triapine®; these potential risks may also apply to other agents used in this study * Patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy; therefore, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with Triapine® or other agents administered during the study; appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated * Patients with known G6PD deficiency are excluded * Patients with a history of myocardial infarction or severe pulmonary disease requiring oxygen are excluded * Because of the potential for enzyme-inducing anticonvulsant agents (EIACAs) to alter the metabolism and pharmacokinetics of irinotecan, patients who are taking EIACAs are excluded * Metastatic brain or meningeal tumors unless the subject is \> 6 months from definitive therapy, had a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry; also the patient must not be undergoing acute steroid therapy or taper * Patients with UGT1A1 7/7 genotype are excluded


Study Plan

Find out more about all the medication administered in this study, their detailed description and what they involve.
Treatment Groups
Study Objectives
One single intervention group 

is designated in this study

This study does not include a placebo group 

Treatment Groups
Group I
Experimental
Patients receive irinotecan IV over 1 hour on day 1 and 3-AP (Triapine®) IV over 2 hours on days 1-3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of irinotecan and 3-AP (Triapine®) until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 6 additional patients are treated at that dose.

Given IV

Given IV

Correlative studies

Correlative studies
Study Objectives
Primary Objectives

Hematologic toxicity measures of thrombocytopenia, neutropenia and leukopenia will be assessed using the continuous variables as the outcome measures (primarily nadir and percent change from baseline values). Nonhematologic toxicities such as diarrhea and stomatitis will be evaluated via the ordinal CTC standard toxicity grading only. Frequency distributions and other descriptive measures will form the basis of the analysis of these variables.
Secondary Objectives

Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease.

Study Centers

These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.
This study has 1 location
Suspended
University of Wisconsin Hospital and ClinicsMadison, United StatesSee the location

CompletedOne Study Center
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