Combretastatin A4 Phosphate in Treating Patients With Advanced Anaplastic Thyroid Cancer

Study Overview
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Brief Summary
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RATIONALE: Combretastatin A4 phosphate may stop the growth of anaplastic thyroid cancer by stopping blood flow to the tumor. PURPOSE: This phase II trial is studying how well combretastatin A4 phosphate works in treating patients with advanced recurrent or metastatic anaplastic thyroid cancer.

Detailed Description
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OBJECTIVES: Determine the objective response rate of patients with advanced anaplastic thyroid cancer treated with combretastatin A4 phosphate. Determine whether this drug alters the natural history of anaplastic thyroid cancer, in terms of doubling the median survival from 4-6 months to 12 months, in these patients. Determine the safety profile of this drug in these patients. Correlate clinical response with pretreatment tumor microvessel density and immature vessel staining, changes in sICAM-1 levels over the course of treatment, and pharmacokinetic parameters in patients treated with this drug. OUTLINE: This is a multicenter study. Patients receive combretastatin A4 phosphate IV over 10 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) receive 2 courses beyond documentation of the CR. Patients are followed monthly. PROJECTED ACCRUAL: A total of 32 patients will be accrued for this study within 18-24 months.

Official Title
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Phase II Trial Of Combretastatin A-4 Phosphate (CA4P) In Advanced Anaplastic Carcinoma Of The Thyroid

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Drug: fosbretabulin disodium


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed* anaplastic or poorly differentiated variant thyroid cancer, including 1 of the following: Recurrent/regionally advanced disease no longer amenable to definitive curative surgery or radiotherapy Untreated metastatic disease NOTE: *If original/diagnostic tumor blocks are unavailable, tumor must be accessible for pretreatment core needle biopsy Must have relapsed or progressed during or after prior combined modality therapy (e.g., systemic chemotherapy and radiotherapy) for regionally advanced (but not metastatic) disease Measurable or evaluable disease Patent trachea and airway by screening direct and indirect laryngoscopy* NOTE: *For patients with bulky thyroid/neck masses and/or suspected airway obstruction No active brain metastases, as evidenced by any of the following: Symptomatic involvement Cerebral edema by CT scan or MRI Radiographic evidence of progression since definitive therapy Continued requirement for corticosteroids PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-2 Life expectancy At least 12 weeks Hematopoietic Absolute granulocyte count at least 1,500/mm^3 Platelet count at least 75,000/mm^3 Hemoglobin at least 8.5 g/dL Hepatic Bilirubin no greater than 1.5 times upper limit of normal (ULN) ALT and AST no greater than 3.5 times ULN Renal Creatinine no greater than 1.5 times ULN Cardiovascular LVEF at least 50% by MUGA EKG normal No evidence of prior myocardial infarction (e.g., significant Q waves), QTc greater than 450 msec, or other clinically significant abnormalities No history of angina (even if controlled by medication) No congestive heart failure No uncontrolled atrial arrhythmias No clinically significant arrhythmias, including any of the following: Conduction abnormalities Nodal junctional arrhythmias and dysrhythmias Sinus bradycardia or tachycardia Supraventricular arrhythmias Atrial fibrillation or flutter Syncope or vasovagal episodes No significant heart wall abnormality or heart muscle damage by MUGA No uncontrolled hypertension (blood pressure consistently greater than 150 mm Hg systolic and 100 mm Hg diastolic regardless of medication) Patients with previous hypertension are allowed provided there is clinical documentation of controlled blood pressure for 2 months prior to study enrollment No symptomatic peripheral vascular disease No symptomatic cerebrovascular disease Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No grade 2 or greater preexisting motor or sensory peripheral neuropathy No uncontrolled hypokalemia or hypomagnesemia No concurrent serious infection No other nonmalignant medical illness that is uncontrolled or whose control may be jeopardized by study therapy No psychiatric disorders or other conditions that would preclude study compliance PRIOR CONCURRENT THERAPY: Biologic therapy No concurrent biologic therapy No concurrent immunotherapy No concurrent prophylactic colony-stimulating factors (e.g., filgrastim [G-CSF] or sargramostim [GM-CSF]) Chemotherapy See Disease Characteristics At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) No other concurrent chemotherapy Endocrine therapy See Disease Characteristics No concurrent hormonal therapy, except any of the following: Gonadotropin-releasing hormone agonists for hormone-refractory prostate cancer Hormone replacement therapy Oral contraceptives Megestrol for anorexia/cachexia Radiotherapy See Disease Characteristics More than 4 weeks since prior radiotherapy with progressive disease beyond radiation ports No prior radiotherapy to more than 30% of the bone marrow No concurrent radiotherapy Surgery See Disease Characteristics More than 4 weeks since prior major surgery Other At least 6 weeks since other prior therapy associated with delayed toxicity No prior therapy for metastatic disease No concurrent medication(s) known to prolong the QTc interval, unless medication(s) can be held for at least 72 hours before, during, and for at least 6 hours after study drug administration No other concurrent investigational therapy No other concurrent antineoplastic or cytotoxic therapy

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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: fosbretabulin disodium|Combretastatin A4 phosphate IV over 10 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) receive 2 courses beyond documentation of the CR.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median survival |  | every 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective disease response |  | every 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anaplastic thyroid cancer, recurrent thyroid cancer