Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

RATIONALE: 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.

PURPOSE: 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.

Further Study Information

OBJECTIVES:

Primary

• Determine the maximum tolerated dose of 3-AP (Triapine^®) when administered with doxorubicin in patients with metastatic or refractory solid tumors.

Secondary

• Determine the toxicity profile of this regimen in these patients.

• Determine any antitumor activity of this regimen in these patients.

• Determine the pharmacokinetic profile of this regimen in these patients.

OUTLINE: This is a dose-escalation study of 3-AP (Triapine^®).

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 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, an additional 6 patients are treated at that dose level.

Patients are followed until disease progression.

PROJECTED ACCRUAL: A total of 3-36 patients will be accrued for this study.

Eligibility Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed solid tumor

• Metastatic or unresectable disease

• Measurable or evaluable disease

• Not amenable to available standard curative or palliative chemotherapy

• No known brain metastasis

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• More than 12 weeks

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3

• Platelet count ≥ 100,000/mm^3

• WBC ≥ 3,000/mm^3

• No G6PD deficiency (i.e., ≥ lower limit of normal)

Hepatic

• AST/ALT ≤ 2.5 times upper limit of normal

• Bilirubin normal

Renal

• Creatinine ≤ 1.5 mg/dL OR

• Creatinine clearance ≥ 60 mL/min

Cardiovascular

• LVEF > 45%

• No symptomatic congestive heart failure

• No unstable angina pectoris

• No cardiac arrhythmia

Pulmonary

• Oxygen saturation 95-100%

• No severe pulmonary disease requiring oxygen therapy

Other

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for 30 days after study treatment

• No prior allergic reaction to compounds of similar chemical or biological composition to 3-AP (Triapine®) or any other study agent

• No other concurrent uncontrolled illness

• No active or ongoing infection

• No psychiatric illness or social situation that would preclude study compliance

• No toxicity > grade 1 from prior therapy

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF) during course 1 of study treatment

• Concurrent G-CSF and GM-CSF allowed during subsequent courses at the discretion of the principal investigator

Chemotherapy

• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered

• No prior anthracyclines

Endocrine therapy

• Not specified

Radiotherapy

• More than 4 weeks since prior radiotherapy and recovered

• No prior radiotherapy to more than 25% of bone marrow

Surgery

• Not specified

Other

• No other concurrent investigational agents

• No concurrent combination antiretroviral therapy for HIV-positive patients

Trial Contact Information

Trial Lead Organizations/Sponsors

University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

George Wilding

Study Chair

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00079014
Information obtained from ClinicalTrials.gov on December 14, 2011

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