• Maximum tolerated dose [ Designated as safety issue: Yes ]
  
• Dose-limiting toxicity [ Designated as safety issue: Yes ]
  

• Pharmacokinetics [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Determine the maximum tolerated dose of batracylin in patients with metastatic or unresectable solid tumors or lymphoma who have a slow acetylator NAT-2 genotype.
• Determine the dose-limiting toxicities and toxicity profile of this regimen in these patients.

Secondary

• Assess, preliminarily, the antitumor activity of this regimen in these patients.
• Correlate polymorphisms in patients with slow acetylator NAT-2 genotypes (NAT-2*5, NAT-2*6, NAT-2*7, and NAT-2*14) with pharmacokinetics results.
• Determine the pharmacokinetics of this regimen.
• Evaluate the interpatient variability and toxicity ratio.

OUTLINE: This is a dose-escalation study.

Patients receive oral batracylin on days 1-7. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 1-6 patients receive escalating doses of batracylin 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.

Peripheral blood samples are collected on days 1, 3, and 7 of the first course and on day 1 of subsequent courses for pharmacokinetic and other research studies.

After completion of study treatment, patients are followed for 4 weeks.

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

DISEASE CHARACTERISTICS:

• Histologically confirmed solid tumors or lymphoma

  • Metastatic or unresectable disease
• Measurable or evaluable disease
• Standard curative measures do not exist or are associated with minimal patient survival benefit
• Must have a slow acetylator NAT-2 genotype, defined as NAT-2*5, NAT-2*6, NAT-2*7, or NAT-2*14
• No known brain metastases, except for brain metastases that have remained stable for ≥ 6 months after treatment and that do not require steroids or antiseizure medications

PATIENT CHARACTERISTICS:

• ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
• Life expectancy > 3 months
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Bilirubin ≤ 1.5 times upper limit of normal (ULN) (≤ 2.5 mg/dL in patients with Gilbert's syndrome)
• AST and ALT ≤ 2.5 times ULN
• Creatinine < 1.5 times ULN OR creatinine clearance ≥ 60 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception before, during, and for 2 months after completion of study treatment

• No clinically significant illnesses including, but not limited to, any of the following:

  • Active or uncontrolled infection
  • Immune deficiencies
  • Confirmed HIV infection
  • Hepatitis B or hepatitis C
  • Uncontrolled diabetes
  • Uncontrolled hypertension
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Myocardial infarction within the past 6 months
  • Uncontrolled cardiac arrhythmia
  • Psychiatric illness or social situation that would preclude study compliance

PRIOR CONCURRENT THERAPY:

• Recovered from all prior therapy
• At least 2 weeks since prior batracylin used in an exploratory IND/phase 0 study
• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas, mitomycin C, or 7-hydroxystaurosporine)
• More than 4 weeks since prior biologic therapy
• At least 1 month since prior radiation therapy or major surgery
• No other concurrent investigational agents
• No concurrent protease inhibitors
• Concurrent bisphosphonates for any cancer allowed
• Concurrent androgen-deprivation therapy for prostate cancer allowed