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

Study Overview
=================
Brief Summary
-----------------
RATIONALE: SU5416 may stop the growth of head and neck cancer by stopping blood flow to the tumor. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining SU5416 with chemotherapy may kill more cancer cells. PURPOSE: Phase I trial to study the effectiveness of SU5416 and paclitaxel in treating patients who have recurrent, locally advanced, or metastatic cancer of the head and neck.

Detailed Description
-----------------
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.

Official Title
-----------------
A Phase I Pharmacokinetic, Pharmacodynamic, and Clinical Study of the Combination of the Angiogenesis Inhibitor SU5416 and Paclitaxel in Recurrent or Metastatic Carcinoma of the Head and Neck

Conditions
-----------------
Head and Neck Cancer

Intervention / Treatment
-----------------
* Drug: paclitaxel
* Drug: semaxanib


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: paclitaxel|Patients receive paclitaxel IV over one hour on day 1. Treatment continues weekly in the absence of disease progression or unacceptable toxicity.|
|Drug: semaxanib|Patients receive SU5416 IV over one hour on days 1 and 4. Treatment continues weekly in the absence of disease progression or unacceptable toxicity.|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the maximum tolerated dose and safety of SU5416 and paclitaxel. |  | Treatment continues weekly in the absence of disease progression or unacceptable toxicity. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
thyroid gland medullary carcinoma, anaplastic thyroid cancer, recurrent thyroid cancer, recurrent salivary gland cancer, recurrent metastatic squamous neck cancer with occult primary, stage III follicular thyroid cancer, metastatic squamous neck cancer with occult primary squamous cell carcinoma, recurrent hypopharyngeal cancer, stage III adenoid cystic carcinoma of the oral cavity, recurrent squamous cell carcinoma of the lip and oral cavity, recurrent verrucous carcinoma of the oral cavity, recurrent mucoepidermoid carcinoma of the oral cavity, recurrent adenoid cystic carcinoma of the oral cavity, recurrent squamous cell carcinoma of the oropharynx, recurrent lymphoepithelioma of the oropharynx, recurrent squamous cell carcinoma of the nasopharynx, recurrent lymphoepithelioma of the nasopharynx, recurrent squamous cell carcinoma of the hypopharynx, recurrent squamous cell carcinoma of the larynx, recurrent verrucous carcinoma of the larynx, recurrent squamous cell carcinoma of the paranasal sinus and nasal cavity, recurrent inverted papilloma of the paranasal sinus and nasal cavity, recurrent esthesioneuroblastoma of the paranasal sinus and nasal cavity