3-AP and Doxorubicin In Treating Patients With Metastatic or Refractory Solid Tumors

NCT00079014 | Completed Phase 1

• 6 other identifiers: NCI-2013-00011CO 03904WCCC-CO-03904NCI-6266P30CA014520U01CA062491
• 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 3-AP and doxorubicin in treating patients with metastatic or refractory solid tumors. Drugs used in chemotherapy, such as doxorubicin, 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 tumor cell growth and may help doxorubicin kill more cancer 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 Common Toxicity Criteria (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, doxorubicin hydrochloride)

EXPERIMENTAL

Patients receive doxorubicin IV over 15 minutes on day 1 and 3-AP (Triapine®) IV over 2 hours on days 1-4. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of 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, an additional 6 patients are treated at that dose level.

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

Interventions

triapine DRUG

Given IV

Also known as: 3-AP, OCX-191

Treatment (triapine, doxorubicin hydrochloride)

doxorubicin hydrochloride DRUG

Given IV

Also known as: ADM, ADR, Adria, Adriamycin PFS, Adriamycin RDF

Treatment (triapine, doxorubicin hydrochloride)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (triapine, doxorubicin hydrochloride)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (triapine, doxorubicin 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 anthracyclines
• 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 \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal
• Patients must have LVEF \> 45%
• 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
• Patients must have measurable or evaluable disease
• 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

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
• Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
• 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 severe pulmonary disease requiring oxygen and patients with baseline hypoxia (\< 95% oxygen saturations) 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; Doxorubicin

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

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: March 8, 2004
• First Posted: March 9, 2004
• Study Start: January 1, 2004
• Primary Completion: July 1, 2008
• Last Updated: May 16, 2013

Record last verified: 2013-05

Locations

US (1)