MS 209 Plus Docetaxel in Treating Patients With Advanced Solid Tumors

Phase I Study to Determine the Safety of MS-209 in Combination With Docetaxel in Patients With a Solid Progressive Tumor

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of MS 209 plus docetaxel in treating patients who have advanced solid tumors.

OBJECTIVES:

• Determine the maximum tolerated dose of oral MS-209 when given with docetaxel IV in patients with advanced solid malignant tumors.
• Assess the toxicity of this regimen in these patients.

OUTLINE: This is a dose escalation, multicenter study of MS-209.

Patients receive docetaxel IV over 1 hour on day 1 of a 3 week course. On day 1 of the 2nd course, patients receive MS-209 orally followed by docetaxel IV over 1 hour. Treatment is repeated every 3 weeks for 4-7 courses (including course with docetaxel alone). Treatment continues in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of MS-209 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 3 or 3 of 6 patients experience dose limiting toxicities.

Patients are followed every 6 weeks.

PROJECTED ACCRUAL: Approximately 3-30 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed advanced malignant solid tumor

  • No gastric cancer

• No brain involvement or leptomeningeal disease

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• At least 3 months

Hematopoietic:

• Neutrophil count at least 2,000/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 11.2 g/dL

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST and ALT no greater than 2.5 times ULN
• Alkaline phosphatase no greater than 2.5 times ULN

Renal:

• Creatinine no greater than 1.4 mg/dL

Cardiovascular:

• Normal cardiac function
• Left ventricular ejection fraction normal

Other:

• No digestive disease that hampers absorption
• No unstable systemic disease or uncontrolled infection that precludes study
• No psychological, familial, sociological, or geographical condition that precludes compliance
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 4 weeks since prior immunotherapy

Chemotherapy:

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)
• No prior docetaxel
• No other concurrent chemotherapy

Endocrine therapy:

• At least 4 weeks since prior hormonal therapy

Radiotherapy:

• At least 4 weeks since prior radiotherapy (6 weeks if extensive)

Surgery:

• Not specified

Other:

• No other concurrent anticancer drugs
• No other concurrent investigational therapies
• No H2-blockers, proton pump inhibitors, sucralfate or any other drug that would impair absorption
• No concurrent drugs exhibiting liver, kidney, heart or lung toxicity
• No concurrent MDR-modulating drugs (e.g., calcium antagonists, immunosuppressives)
• No concurrent antifungals (ketoconazole, fluconazole) or antibiotics (clarithromycin, erthromycin) that interfere with MS-209 metabolism