Study of Combretastatin and Paclitaxel/Carboplatin in the Treatment of Anaplastic Thyroid Cancer

Anaplastic Thyroid Cancer Clinical Trial

— FACT  

Official title:

A 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 [FACT]

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00507429
• Other study ID #: OXC4T4-302
• Status: Terminated
• Phase: Phase 2/Phase 3
• First received: July 25, 2007
• Last updated: May 12, 2014
• Start date: August 2007
• Est. completion date: November 2011

Study information

• Verified date: February 2014
• Source: OXiGENE
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Description:

Anaplastic thyroid carcinoma (ATC) is a high-grade neoplasm, characterized by an aggressive clinical course with brief survival, and refractoriness to currently available local and systemic modalities of treatment. There is no standard therapy for ATC, and no randomized comparative trials have been known to be conducted in this disease. One potential strategy is to combine the anti-tumor activity of the vascular disrupting agent combretastatin with conventional cytotoxic agents. This study will compare the overall survival of ATC patients treated with the triplet combination of combretastatin, paclitaxel, and carboplatin compared with the doublet treatment of paclitaxel and carboplatin.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 80
• Est. completion date: November 2011
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Anaplastic thyroid carcinoma histologically or cytologically confirmed by a pathology review

• 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

• Systemic therapy is limited to one chemotherapy regimen that is clearly administered contiguously, (i.e., in an uninterrupted primary therapeutic approach)

• Prior radiation: 3 weeks must have elapsed since radiation and disease must be present beyond radiation ports

• Minimum of 3 weeks must have elapsed from the time of last chemotherapy prior to the first dose of study drug

• 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

• ECOG Performance Score less than or equal to 2

• Adequate bone marrow reserve as evidenced by absolute neutrophil count (ANC) greater than 1,500/microL, platelet count greater than 75,000/microL.

• Adequate renal function as evidenced by serum creatinine less than or equal to 2.0 mg/dL (less than 177 micromol/L)

• 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)

• No clinically important sequelae from any prior surgery or radiotherapy.

Exclusion Criteria:

• Tumors confined to the thyroid.

• 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

• Patients who receive chemotherapy for metastatic disease after completion of a combined modality approach.

• History of malignancies other than ATC except 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

• Known hypersensitivity to CA4P, paclitaxel or carboplatin, or any of their components

• Receiving concurrent investigational therapy or who have received investigational therapy for any indication within 28 days of the first scheduled day of dosing

• Greater than Grade 2 peripheral neuropathy

• History of prior cerebrovascular event, including transient ischemic attack

• Uncontrolled hypertension (blood pressure greater than 150/100 mm Hg despite medication)

• Symptomatic vascular disease (e.g. intermittent claudication)

• 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

• History of torsade de pointes

• Bradycardia (less than 60 b/m), heart block (excluding 1st degree block, being PR interval prolongation only), and congenital long QT syndrome

• Any ventricular arrhythmias, or new ST segment elevation or depression or Q wave on ECG

• Ejection fractions less than normal (i.e. less than 45%)

• QTc prolongation greater than 450 ms

• Requirement of any drugs known to prolong the QTc interval, including anti-arrhythmic medications

• Potassium concentrations below 4.0 mEq/dL and magnesium concentrations below 1.8 mg/dL despite being on an electrolyte supplement

• Requirement of any drugs known to prolong the QTc interval

• History of solid organ transplant or bone marrow transplant

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anaplastic Thyroid Cancer
• Thyroid Diseases
• Thyroid Neoplasms

Intervention

Drug:
• CA4P
CA4P 60mg/m squared for Days 1, 8, 15 for 6 cycles
• paclitaxel
200mg/m squared on Day 1
• carboplatin
6 AUC on Day 1 following paclitaxel

Locations

Country	Name	City	State
Belarus	Belarus National Medical University	Minsk
Bulgaria	Regional Oncology Dispensary with Inpatient Sector	Plodiv
Bulgaria	Specialized Hospital for Active Treatment of Oncology	Sofia
Bulgaria	Universtiy Multiprofile Hospital, ISUI, Clinic of Oncotherapy	Sofia
Egypt	University Hospital, Cairo	Cairo
India	Kidwai Memorial Hospital	Bangalore	Karnataka
India	Mediciti Hospital	Hyderabaad	Andhra Pradesh
India	Shirdi Sai Baba Cancer Hospital	Manipal	Karnataka
India	Tata Memorial Centre	Mumbai	Maharashtra
India	All India Institute of Medical Sciences	New Delhi	Delhi
India	Apollo Cancer Institute	New Delhi	Delhi
India	Ruby Hall Clinic	Pune	Maharashtra
India	Christian Medial College	Vellore	Tamil Nadu
Israel	Telaviv Sourasky Medical Center, Head and Neck Service Division of Oncology	Tel-Aviv
Italy	Lo Studio E la Cura	Milano
Italy	INT Napoli Fondazione Pascale	Napoli
Italy	Istituto Oncologico Veneto (IOV) - IRCCS	Padova
Italy	Azienda Ospedaliero - Universitaria Pisana	Pisa
Poland	Zaklad Medyczny Nuklearnej i Endykrynologii	Gliwice
Poland	Klinika Nowotworow Glowy i Szyji	Warszawa
Romania	Institutul Oncologic	Cluj-Napoca
Romania	SC Meditech SRL	Craiova
Romania	Centr of Medical Oncology	Iasi
Romania	Clinical County Hospital Sibiu	Sibiu
Romania	Emergency Clinical County Hospital "Sf. loan cel Nou"	Suceava
Russian Federation	City Clinical Oncology Dispensary	Saint Petersburg
Ukraine	Ukrainian Academy of Medical Science	Lomonosova 33/43	Kiev
Ukraine	Regional Clinical Oncology Dispensary	Lvov
United Kingdom	Beatson Oncology Centre, Gartnavel General Hospital	Glasgow	Scotland
United Kingdom	Royal Marsden Hospital and Institute of Cancer Research	London
United Kingdom	Southampton Hospital Oncology Centre	Southampton
United States	Winship Cancer Institute, Emory University	Atlanta	Georgia
United States	University of Colorado Cancer Center	Aurora	Colorado
United States	Sidney Kimmel Comprehensive Cancer Care Center at John Hopkins	Baltimore	Maryland
United States	Ireland Cancer Center/Division od Hematology	Cleveland	Ohio
United States	University of Texas M.D. Anderson Cancer Center	Houston	Texas
United States	USC/Norris Comprehensive Cancer Center	Los Angeles	California
United States	University of Minnesota Otolaryngology Department	Minneapolis	Minnesota
United States	West Virginia University	Morgantown	West Virginia
United States	Yale University, School of Medicine	New Haven	Connecticut
United States	Oregon Health and Science University	Portland	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
OXiGENE

Countries where clinical trial is conducted

United States,  Belarus,  Bulgaria,  Egypt,  India,  Israel,  Italy,  Poland,  Romania,  Russian Federation,  Ukraine,  United Kingdom, 

References & Publications (7)

Ain KB. Anaplastic thyroid carcinoma: behavior, biology, and therapeutic approaches. Thyroid. 1998 Aug;8(8):715-26. Review. — View Citation

Cooney MM, Savvides P, Agarwala SS, Wang D, Flick S, Bergant S, Bhatka S,Fu P, Subbiah V, Lavertu P, Ortiz J, and Remick S. Phase II study of combretastatin A4 phosphate (CA4P) in patients with advanced anaplastic thyroid carcinoma. J Clinical Oncology, 2006 Vol. 24, 5580.

De Crevoisier R, Baudin E, Bachelot A, Leboulleux S, Travagli JP, Caillou B, Schlumberger M. Combined treatment of anaplastic thyroid carcinoma with surgery, chemotherapy, and hyperfractionated accelerated external radiotherapy. Int J Radiat Oncol Biol Phys. 2004 Nov 15;60(4):1137-43. — View Citation

Horsman MR, Siemann DW. Pathophysiologic effects of vascular-targeting agents and the implications for combination with conventional therapies. Cancer Res. 2006 Dec 15;66(24):11520-39. Review. — View Citation

Patel KN, Shaha AR. Poorly differentiated and anaplastic thyroid cancer. Cancer Control. 2006 Apr;13(2):119-28. Review. — View Citation

Siemann DW, Chaplin DJ, Horsman MR. Vascular-targeting therapies for treatment of malignant disease. Cancer. 2004 Jun 15;100(12):2491-9. Review. — View Citation

Yeung SC, She M, Yang H, Pan J, Sun L, Chaplin D. Combination chemotherapy including combretastatin A4 phosphate and paclitaxel is effective against anaplastic thyroid cancer in a nude mouse xenograft model. J Clin Endocrinol Metab. 2007 Aug;92(8):2902-9. Epub 2007 Jun 5. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival		From randomization to date last known alive	No
Secondary	To Determine Progression Free Survival		from randomization through end of study visit	No
Secondary	To Determine Percentage of 1 Year Survival		from randomization through end of study visit	No

External Links

•   Link to Thyroid Cancer Survivors website
•   OXiGENE (Sponsor) Website