Combretastatin A4 Phosphate in Treating Patients With Advanced Anaplastic Thyroid Cancer

Case Comprehensive Cancer Center (Case CCC)

Status and phase

Completed

Phase 2

Conditions

Head and Neck Cancer

Treatments

Drug: fosbretabulin disodium

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00060242

CASE-CWRU-ICC-2302 (Other Identifier)

P30CA043703 (U.S. NIH Grant/Contract)

ICC2302

Details and patient eligibility

About

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.

Full description

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.

Enrollment

26 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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