FACT Clinical Trial: Fosbretabulin in Anaplastic Cancer of the Thyroid

Who May Be a Candidate

Oncology (cancer) specialists now are enrolling candidates for a clinical trial to study the safety and effectiveness of a novel agent in the treatment of Anaplastic Thyroid Cancer (ATC). This clinical trial is being conducted in the United States, Eastern and Western Europe, India, and the Middle East.

Candidates for this clinical trial are 18 years of age or older, diagnosed with ATC from a biopsy, are strong enough to walk and care for basic personal needs, and expected to live 12 weeks or longer. Details about the study's inclusion and exclusion criteria are provided below.

Product Being Studied

This clinical trial is being conducted to study Fosbretabulin (ZYBRESTAT), a tumor vascular disrupting agent administered in combination with chemotherapy. All patients enrolled will receive standard chemotherapy with carboplatin and paclitaxel.

Patients will be randomly assigned to the treatment arm (Fosbretabulin (ZYBRESTAT) plus carboplatin and paclitaxel) versus the control arm (carboplatin and paclitaxel) on a 2:1 basis that will result in 2/3 of participants receiving the investigational product in combination with chemotherapy and 1/3 receiving chemotherapy alone.

Clinical Trial Sponsor

Oxigene, Inc.

Purpose and Objective

The purpose of the study is to determine the safety and efficacy of fosbretabulin combined with paclitaxel and carboplatin in the treatment of anaplastic thyroid cancer (ATC).

Recruiting Locations (United States)

United States, Eastern and Western Europe, India, and the Middle East

Eligibility, Inclusion and Exclusion Criteria

Ages Eligible for Study: 18 years and older
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No

Inclusion Criteria

1. Patients must have anaplastic thyroid carcinoma histologically or cytologically confirmed by a pathology review. Mixed type histology is allowed.
2. Patients may have been refractory to or progressed during or after therapy, or relapsed within 6 months following initial combined modality therapy (usually including systemic chemotherapy and radiation) for regionally advanced disease.
3. Where patients have received combined modality therapy for metastatic disease, systemic therapy is limited to one chemotherapy regimen that is clearly administered contiguously, (i.e., in an uninterrupted primary therapeutic approach). Patients who receive chemotherapy for metastatic disease after a combined modality approach are ineligible.
4. In patients having received prior head and neck radiation, 3 weeks must have elapsed since radiation.
5. A minimum of 3 weeks must have elapsed from the time a patient last received chemotherapy prior to the first dose of study drug.
6. Patients with bulky thyroid/neck masses and/or suspicion of airway obstruction must undergo screening (indirect and direct laryngoscopy) to ensure patency of the trachea/airway prior to study enrollment and treatment.
7. Patients must have an Eastern Cooperative Oncology Group (ECOG) Performance Score less than or equal to 2.
8. Life expectancy greater than or equal to 12 weeks.
9. Patients must have adequate bone marrow reserve as evidenced by: -Absolute neutrophil count (ANC) greater than 1,500/microL. Platelet count greater than 100,000/microL. -Patients must have adequate renal function as evidenced by serum creatinine less than or equal to 2.0 mg/dL (less than 177 micromol/L).
10. Patients must have adequate hepatic function as evidenced by: -Serum total bilirubin less than 2X greater than the upper limit of normal (ULN) (less than3X ULN in patients with liver metastases). -AST (aspartate aminotransferase)/ALT (alanine aminotransferase) less than or equal to 3X the ULN for the local reference lab (less than or equal to 5X the ULN for patients with liver metastases).
11. Patients or their legal representatives must be able to read, understand and provide written informed consent to participate in the trial.
12. Patients must have no clinically important sequelae from any prior surgery or radiotherapy.
13. All women of childbearing potential must have a negative serum pregnancy test.
14. Women of childbearing potential as well as fertile men and their partners must agree to use an effective form of contraception during the study and for 90 days following the last dose of study medication. (An effective form of contraception is an oral contraceptive or a double barrier method.)

Exclusion Criteria

1. Patients with tumors confined to the thyroid.
2. Patients with an uncontrolled active infection.
3. Clinically evident brain metastasis, including symptomatic involvement, evidence of cerebral edema by CT or MRI, radiographic evidence of progression of brain metastasis since definitive therapy, or continued requirement for corticosteroids.
4. Patients who receive chemotherapy for metastatic disease after completion of a combined modality approach.
5. Patients with history of malignancies other than ATC except patients with curatively treated basal cell carcinoma of the skin, cervical intra-epithelial neoplasia, or localized prostate cancer with a current PSA of less than 4.0 mg/dL or microg/L. (Patients with other curatively treated malignancies who have no evidence of metastatic disease will be considered after discussion with the Medical Monitor.)
6. Patients with known hypersensitivity to CA4P, paclitaxel or carboplatin, or any of their components.
7. Patients who are receiving concurrent investigational therapy or who have received investigational therapy for any indication within 28 days of the first scheduled day of dosing. (Investigational therapy is defined as treatment for which there is currently no regulatory authority approved indication.)
8. Patients with greater than Grade 2 peripheral neuropathy.
9. Patients who are pregnant or lactating.
10. Patients with a history of prior cerebrovascular event, including transient ischemic attack.
11. Patients with uncontrolled hypertension defined as blood pressure greater than 150/100 mm Hg despite medication.
12. Patients with symptomatic vascular disease (e.g. intermittent claudication)
13. Patients with a history of unstable angina pectoris pattern, myocardial infarction (including non-Q wave MI) within the past 6 months, or NYHA Class III and IV congestive heart failure.
14. Patients with a history of torsade de pointes.
15. Patients with bradycardia (less than 60 b/m), heart block (excluding 1st degree block, being PR interval prolongation only), and congenital long QT syndrome.
16. Patients with any ventricular arrhythmias, or new ST segment elevation or depression or Q wave on ECG.
17. Patients with ejection fractions less than normal (i.e. less than 45%).
18. Patients with QTc prolongation greater than 450 ms.for males and 470 ms for females.
19. Patients requiring any drugs known to prolong the QTc interval, including anti-arrhythmic medications.
20. Patients with potassium concentrations below 4.0 mEq/dL and magnesium concentrations below 1.8 mg/dL despite being on an electrolyte supplement.
21. Patients requiring any drugs known to prolong the QTc interval.
22. Patients with any other intercurrent medical condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results.
23. Patients with a history of solid organ transplant or bone marrow transplant.

ClinicalTrials.gov Identifier: NCT00507429

Study ID Numbers: OXC4T4-302

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Official Title: A Multicenter, Open-label, Randomized, Phase II/III Study to Evaluate the Safety and Efficacy of Combretastatin A-4 Phosphate in Combination With Paclitaxel and Carboplatin in Comparison With Paclitaxel and Carboplatin Against Anaplastic Thyroid Carcinoma

ClinicalTrials.gov Official Website: http://clinicaltrials.gov/ct2/show/NCT00507429