SU5416 and Paclitaxel in Treating Patients With Recurrent, Locally Advanced or Metastatic Cancer of the Head and Neck

OBJECTIVES:

• Determine the maximum tolerated dose and safety of SU5416 and paclitaxel in patients with recurrent or metastatic head and neck cancer.
• Determine the antiangiogenesis effect of this combination regimen in these patients.
• Determine the toxicity, pharmacodynamic effects, and pharmacokinetic parameters of this combination.

OUTLINE: This is a dose escalation study.

Patients receive paclitaxel IV over one hour on day 1 and SU5416 IV over one hour on days 1 and 4. Treatment continues weekly in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of paclitaxel and SU5416 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 6 patients experience dose limiting toxicities.

PROJECTED ACCRUAL: A total of 34 patients will be accrued for this study within 9-15 months.

DISEASE CHARACTERISTICS:

• Metastatic or loco-regionally recurrent malignancy of the head and neck (including salivary gland and thyroid) that is incurable by surgery or radiotherapy
• At least two distinct tumor masses OR
• One tumor mass at least 3 cm in diameter
• No brain metastases
• No pulmonary metastases as only site of disease

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• At least 12 weeks

Hematopoietic:

• WBC at least 3,500/mm3
• Granulocyte count at least 1,500/mm3
• Platelet count at least 100,000/mm3
• Hemoglobin greater than 9.0 g/dL

Hepatic:

• PT and PTT normal OR
• INR ratio less than 1.1
• Bilirubin less than 1.5 mg/dL
• AST and ALT less than 2 times upper limit of normal

Renal:

• Creatinine less than 1.5 mg/dL
• Creatinine clearance greater than 60 mL/min

Cardiovascular:

• No New York Heart Association class III or IV heart disease
• No uncompensated coronary artery disease
• No history of myocardial infarction or severe or unstable angina within the past 6 months
• No severe peripheral vascular disease
• No deep venous thrombosis or arterial thrombosis within the past 6 months
• No known hypercoagulable syndrome with predisposition to venous or arterial clots

Pulmonary:

• No pulmonary embolism within the past 6 months

Other:

• No prior cerebral hemorrhage
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• At least 3 weeks since palliative chemotherapy (6 weeks for mitomycin or nitrosoureas) and recovered
• At least 4 weeks since combined chemoradiotherapy and recovered
• Must be recovered from prior taxanes

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics
• At least 4 weeks since prior large field radiotherapy and recovered

Surgery:

• Not specified