Irinotecan and 3-AP in Treating Patients With Metastatic or Unresectable Solid Tumors

NCT00084877 | Completed Phase 1

• 5 other identifiers: NCI-2013-00013CO 03903NCI-6264WCCC-CO-03903U01CA062491
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial is studying the side effects and best dose of irinotecan and 3-AP in treating patients with metastatic or unresectable solid tumors. Drugs used in chemotherapy such as irinotecan work in different ways to stop tumor cells from dividing so they stop growing or die. 3-AP may stop the growth of tumor cells by blocking the enzymes necessary for their growth and may help irinotecan kill more tumor cells by making them more sensitive to the drug.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Outcome Measures

Primary Outcomes (1)

• Number and severity of toxicity incidents categorized via CTC standard toxicity grading

  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.

  Up to 4 years

Secondary Outcomes (1)

• Number of responses

  Up to 4 years

Study Arms (1)

Treatment (triapine, irinotecan hydrochloride)

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.

Drug: triapine; Drug: irinotecan hydrochloride; Other: laboratory biomarker analysis; Other: pharmacological study

Interventions

triapine DRUG

Given IV

Also known as: 3-AP, OCX-191

Treatment (triapine, irinotecan hydrochloride)

irinotecan hydrochloride DRUG

Given IV

Also known as: Campto, Camptosar, CPT-11, irinotecan, U-101440E

Treatment (triapine, irinotecan hydrochloride)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (triapine, irinotecan hydrochloride)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (triapine, irinotecan hydrochloride)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Interventions

3-aminopyridine-2-carboxaldehyde thiosemicarbazone; Irinotecan

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds

Study Officials

• George Wilding

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2004
• First Posted: June 11, 2004
• Study Start: March 1, 2004
• Primary Completion: July 1, 2008
• Last Updated: May 16, 2013

Record last verified: 2013-05

Locations

US (1)