Know Cancer

forgot password

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

Phase 2
18 Years
Not Enrolling
Head and Neck Cancer

Thank you

Trial Information

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


- 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

Patients are followed monthly.

PROJECTED ACCRUAL: A total of 32 patients will be accrued for this study within 18-24

Inclusion Criteria


- 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



- 18 and over

Performance status

- ECOG 0-2

Life expectancy

- At least 12 weeks


- Absolute granulocyte count at least 1,500/mm^3

- Platelet count at least 75,000/mm^3

- Hemoglobin at least 8.5 g/dL


- Bilirubin no greater than 1.5 times upper limit of normal (ULN)

- ALT and AST no greater than 3.5 times ULN


- Creatinine no greater than 1.5 times ULN


- 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

- No symptomatic peripheral vascular disease

- No symptomatic cerebrovascular disease


- 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


Biologic therapy

- No concurrent biologic therapy

- No concurrent immunotherapy

- No concurrent prophylactic colony-stimulating factors (e.g., filgrastim [G-CSF] or
sargramostim [GM-CSF])


- 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


- See Disease Characteristics

- More than 4 weeks since prior radiotherapy with progressive disease beyond radiation

- No prior radiotherapy to more than 30% of the bone marrow

- No concurrent radiotherapy


- See Disease Characteristics

- More than 4 weeks since prior major surgery


- 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Median survival

Outcome Time Frame:

every 8 weeks

Safety Issue:


Principal Investigator

Panayiotis Savvides, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Ireland Cancer Center at University Hosptials Case Medical Center, Case Comprehensive Cancer Center


United States: Federal Government

Study ID:




Start Date:

February 2003

Completion Date:

January 2008

Related Keywords:

  • Head and Neck Cancer
  • anaplastic thyroid cancer
  • recurrent thyroid cancer
  • Thyroid Neoplasms
  • Head and Neck Neoplasms
  • Carcinoma



Hillman Cancer Center at University of Pittsburgh Cancer Institute Pittsburgh, Pennsylvania  15236
Josephine Ford Cancer Center at Henry Ford Hospital Detroit, Michigan  48202
Ireland Cancer Center at University Hosptials Case Medical Center, Case Comprehensive Cancer Center Cleveland, Ohio  44106-5065