• Maximum tolerated dose at first course [ Designated as safety issue: Yes ]
  

• Toxicity at first and second course [ Designated as safety issue: Yes ]
  
• Antitumor activity at first and second course [ Designated as safety issue: No ]
  

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.

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