SJG-136 in Treating Patients With Advanced Solid Tumors

PRIMARY OBJECTIVES:

I. To determine the toxicities, pharmacokinetic profile and the recommended phase 2 dose of SJG-136 in patients with an advanced solid tumor.

SECONDARY OBJECTIVES:

I. To determine preliminary efficacy data and evaluation of correlative markers of DNA damage and apoptosis in peripheral blood lymphocytes.

OUTLINE: This is an open-label, dose-escalation study.

Patients receive SJG-136 intravenously (IV) over 20 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of SJG-136 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. At least 6 patients are treated at the MTD.

Inclusion criteria

• Histologically confirmed solid tumor

• Advanced disease, defined as metastatic or unresectable disease
• Measurable indicator lesions
• Standard curative or palliative measures do not exist or are no longer effective
• Previously treated CNS metastases allowed provided patient has completed local therapy AND corticosteroids have been discontinued for at least 4 weeks
• No known leptomeningeal metastases
• Performance status - ECOG 0-2
• Performance status - Karnofsky 60-100%
• More than 3 months
• WBC ≥ 3,000/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Bilirubin ≤ 1.0 mg/dL
• AST and ALT ≤ 2.5 times upper limit of normal
• Creatinine < 1.4 mg/dL
• No congestive heart failure
• No recent myocardial infarction
• No unstable angina
• No uncontrolled hypertension
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active infection
• No history of allergic reaction attributed to compounds of similar chemical or biological composition to study drug
• No other significant medical history, unstable medical condition, or unstable systemic disease that would preclude study participation
• At least 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas and 8 weeks for UCN-01)
• At least 4 weeks since prior radiotherapy
• No prior radiotherapy to ≥ 25% of hematopoietic bone marrow
• Recovered from all prior therapy
• At least 4 weeks since prior investigational anticancer drugs
• No other concurrent investigational agents
• No concurrent combination antiretroviral therapy for HIV-positive patients