Flavopiridol in Treating Patients With Recurrent or Metastatic Head and Neck Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase II trial to study the effectiveness of flavopiridol in treating patients who have recurrent or metastatic head and neck cancer.

Detailed Description
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OBJECTIVES: Determine the standard response rate (complete response and partial response) and duration of response in patients with recurrent or metastatic squamous cell carcinoma of the head and neck treated with flavopiridol. Determine the qualitative and quantitative toxic effects of this regimen in these patients. Determine the progression-free and overall survival of patients treated with this regimen. Determine the effects of anti-platelet agents, aspirin and clopidogrel bisulfate, on the pharmacology of flavopiridol in these patients. Determine the effects of prophylactic anticoagulation with anti-platelet agents, aspirin and clopidogrel bisulfate, on the incidence of flavopiridol-related thrombosis in these patients. OUTLINE: Patients receive flavopiridol IV over 1 hour on days 1-5. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive oral aspirin and clopidogrel bisulfate beginning on day 0 and continuing throughout the study. Patients are followed until death. PROJECTED ACCRUAL: A total of 12-37 patients will be accrued for this study within 1-3 years.

Official Title
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A Phase II Trial of Daily Bolus Flavopiridol for Five Consecutive Days in Patients With Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Conditions
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Head and Neck Cancer, Thromboembolism

Intervention / Treatment
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* Drug: acetylsalicylic acid
* Drug: alvocidib
* Drug: clopidogrel bisulfate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically proven squamous cell carcinoma of the head and neck Metastatic disease at diagnosis OR Persistent, metastatic, or recurrent disease after prior definitive surgery and/or radiotherapy No undifferentiated and nonkeratinizing carcinomas, including lymphoepitheliomas of all locations No nasopharynx tumors Bidimensionally measurable disease Patients whose only measurable disease is within a prior radiotherapy port must have clearly progressive disease No metastatic or leptomeningeal CNS disease PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: Not specified Hematopoietic: Platelet count greater than 100,000/mm^3 Absolute granulocyte count greater than 1,500/mm^3 Hepatic: See Other (Prior/Concurrent Therapy) SGOT and SGPT less than 2.5 times normal Bilirubin less than 1.5 times normal No history of hypercoagulopathies (e.g., protein C deficiency, protein S deficiency, or lupus anticoagulant) Renal: Creatinine no greater than 1.5 mg/dL OR Creatinine clearance at least 60 mL/min Calcium no greater than normal No hypercalcemia refractory to bisphosphonates Cardiovascular: No unstable or newly diagnosed angina pectoris No myocardial infarction within the past 6 months No class II-IV congestive heart failure No history of symptomatic carotid disease No concurrent asymptomatic carotid artery occlusion (70% or greater) in one or both arteries by Doppler ultrasound No symptomatic atherosclerosis No thrombotic events within the past 6 months Pulmonary: No aspirin-induced asthma Other: No inability to take aspirin or clopidogrel bisulfate due to contraindications, allergies, or pre-existing medical conditions (e.g., active peptic ulcer disease or history of undiagnosed non-occult, non-hemorrhoidal gastrointestinal or other bleeding sources within the past 6 months) No other prior malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer that is currently in complete remission HIV negative Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 3 months after study PRIOR CONCURRENT THERAPY: Biologic therapy: No concurrent biologic therapy Chemotherapy: At least 4 weeks since prior chemotherapy and recovered No prior flavopiridol No more than 3 prior systemic chemotherapy regimens for recurrent or metastatic disease No other concurrent chemotherapy Endocrine therapy: No concurrent hormonal therapy except oral contraceptives Radiotherapy: See Disease Characteristics At least 4 weeks since prior radiotherapy and recovered No concurrent radiotherapy Surgery: See Disease Characteristics At least 4 weeks since prior surgery and recovered No prior carotid endarterectomy or other revascularization surgery Other: No other concurrent antineoplastic therapies No active anticoagulation with INR 1.5 or greater No low-molecular weight heparin or equivalent Concurrent bisphosphonates for calcium maintenance allowed

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: acetylsalicylic acid|nan|
|Drug: alvocidib|nan|
|Drug: clopidogrel bisulfate|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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thromboembolism, untreated metastatic squamous neck cancer with occult primary, recurrent metastatic squamous neck cancer with occult primary, metastatic squamous neck cancer with occult primary squamous cell carcinoma, stage IV squamous cell carcinoma of the lip and oral cavity, recurrent squamous cell carcinoma of the lip and oral cavity, stage IV squamous cell carcinoma of the oropharynx, recurrent squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the hypopharynx, recurrent squamous cell carcinoma of the hypopharynx, stage IV squamous cell carcinoma of the larynx, recurrent squamous cell carcinoma of the larynx, stage IV squamous cell carcinoma of the paranasal sinus and nasal cavity, recurrent squamous cell carcinoma of the paranasal sinus and nasal cavity, recurrent salivary gland cancer, salivary gland squamous cell carcinoma, stage IV salivary gland cancer