Combretastatin A4 Phosphate in Treating Patients With Advanced Anaplastic Thyroid Cancer

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