Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Combretastatin A4 Phosphate in Treating Patients With Advanced Anaplastic Thyroid Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Completed	18 and over	NCI	CASE-CWRU-ICC-2302 NCT00060242, CASE-2302

Objectives

1. Determine the objective response rate of patients with advanced anaplastic thyroid cancer treated with combretastatin A4 phosphate.
2. 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.
3. Determine the safety profile of this drug in these patients.
4. 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.

Entry 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

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

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/mm³
• Platelet count at least 75,000/mm³
• 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

Expected Enrollment

A total of 32 patients will be accrued for this study within 18-24 months.

Outcomes

Median survival every 8 weeks

Objective disease response every 8 weeks

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.

Mooney CJ, Nagaiah G, Fu P, et al.: A phase II trial of fosbretabulin in advanced anaplastic thyroid carcinoma and correlation of baseline serum-soluble intracellular adhesion molecule-1 with outcome. Thyroid 19 (3): 233-40, 2009.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Case Comprehensive Cancer Center

Scot Remick, MD, Protocol chair		Ph: 216-844-5412

Registry Information
Official Title		Phase II Trial Of Combretastatin A-4 Phosphate (CA4P) In Advanced Anaplastic Carcinoma Of The Thyroid
Trial Start Date		2003-02-25
Registered in ClinicalTrials.gov		NCT00060242
Date Submitted to PDQ		2003-03-25
Information Last Verified		2008-12-31
NCI Grant/Contract Number		CA43703

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