RATIONALE: S-3304 may stop or slow the growth of solid tumors by stopping blood flow to the
PURPOSE: Phase I trial to study the effectiveness of S-3304 in treating patients who have
- 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.
- 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
- 18 and over
- ECOG 0-2
- More than 6 weeks
- Absolute neutrophil count greater than 1,500/mm^3
- Platelet count at least 100,000/mm^3
- Hemoglobin at least 9.0 g/dL
- Bilirubin no greater than 2 times upper limit of normal (ULN)
- Transaminases less than 2.5 times ULN
- Creatinine less than 2.0 mg/dL
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for at least 30 days
- 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:
- At least 4 weeks since prior immunotherapy
- Concurrent stable doses of epoetin alfa are allowed during the second and subsequent
- No other concurrent immunotherapy
- At least 4 weeks since prior chemotherapy
- No concurrent chemotherapy
- 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
- At least 4 weeks since prior radiotherapy
- No concurrent radiotherapy
- No prior significant gastric resection
- 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