S-3304 in Treating Patients With Advanced Solid Tumors

OBJECTIVES:

• Determine the maximum tolerated dose and safety profile of S-3304 in patients with advanced solid tumors.
• Determine the pharmacokinetic profile of this drug in these patients.
• Estimate the starting dose of this drug for subsequent phase II efficacy studies.

OUTLINE: This is a dose-escalation, multicenter study.

Patients receive oral S-3304 twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 6-8 patients receive escalating doses of S-3304 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 or 3 of 8 patients experience dose-limiting toxicity.

Patients are followed at 30 days.

PROJECTED ACCRUAL: A total of 6-28 patients will be accrued for this study within 1 year.

DISEASE CHARACTERISTICS:

• Histologically confirmed solid tumor that failed to respond or relapsed after prior therapy or for which no standard therapy exists
• Biopsy-accessible lesion
• No brain metastasis unless clinically stable and off therapy

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• More than 6 weeks

Hematopoietic:

• Absolute neutrophil count greater than 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 9.0 g/dL

Hepatic:

• Bilirubin no greater than 2 times upper limit of normal (ULN)
• Transaminases less than 2.5 times ULN

Renal:

• Creatinine less than 2.0 mg/dL

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for at least 30 days after study
• Able to tolerate oral medication
• HIV negative
• No AIDS
• No serious underlying gastrointestinal disorders (e.g., recurrent vomiting or inflammatory bowel disease)
• No other serious concurrent illness

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 4 weeks since prior immunotherapy
• Concurrent stable doses of epoetin alfa are allowed during the second and subsequent courses
• No other concurrent immunotherapy

Chemotherapy:

• At least 4 weeks since prior chemotherapy
• No concurrent chemotherapy

Endocrine therapy:

• At least 4 weeks since prior hormonal therapy
• Concurrent stable doses of steroids for prostate cancer are allowed during the second and subsequent courses
• No concurrent hormonal therapy

Radiotherapy:

• At least 4 weeks since prior radiotherapy
• No concurrent radiotherapy

Surgery:

• No prior significant gastric resection

Other:

• Recovered from prior therapy
• At least 4 weeks since other prior investigational antitumor drugs
• No other concurrent investigational antitumor drugs
• Concurrent stable doses of bisphosphonates, cyclo-oxygenase-2 inhibitors, and non-steroidal anti-inflammatory drugs are allowed during the second and subsequent study courses