Clinical trial NCT00507429: Study of Combretastatin and Paclitaxel/Carboplatin in the Treatment of Anaplastic Thyroid Cancer
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]
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Anaplastic Thyroid Cancer
Keywords: thyroid neoplasms
thyroid cancer
thyroid carcinoma
Lead sponsor: Mateon Therapeutics
Sponsor class: INDUSTRY
First posted: 2007-07-26
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Overall Survival
timeFrame: From randomization to date last known alive
Secondary outcomes:
measure: To Determine Progression Free Survival
timeFrame: from randomization through end of study visit
measure: To Determine Percentage of 1 Year Survival
timeFrame: from randomization through end of study visit
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: New Haven
country: United States
facility: Yale University, School of Medicine
state: Connecticut
city: Atlanta
country: United States
facility: Winship Cancer Institute, Emory University
state: Georgia
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Care Center at John Hopkins
state: Maryland
city: Minneapolis
country: United States
facility: University of Minnesota Otolaryngology Department
state: Minnesota
city: Cleveland
country: United States
facility: Ireland Cancer Center/Division od Hematology
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Houston
country: United States
facility: University of Texas M.D. Anderson Cancer Center
state: Texas
city: Morgantown
country: United States
facility: West Virginia University
state: West Virginia
city: Minsk
country: Belarus
facility: Belarus National Medical University
city: Plodiv
country: Bulgaria
facility: Regional Oncology Dispensary with Inpatient Sector
city: Sofia
country: Bulgaria
facility: Specialized Hospital for Active Treatment of Oncology
city: Sofia
country: Bulgaria
facility: Universtiy Multiprofile Hospital, ISUI, Clinic of Oncotherapy
city: Cairo
country: Egypt
facility: University Hospital, Cairo
city: Hyderabaad
country: India
facility: Mediciti Hospital
state: Andhra Pradesh
city: New Delhi
country: India
facility: All India Institute of Medical Sciences
state: Delhi
city: New Delhi
country: India
facility: Apollo Cancer Institute
state: Delhi
city: Bangalore
country: India
facility: Kidwai Memorial Hospital
state: Karnataka
city: Manipal
country: India
facility: Shirdi Sai Baba Cancer Hospital
state: Karnataka
city: Mumbai
country: India
facility: Tata Memorial Centre
state: Maharashtra
city: Pune
country: India
facility: Ruby Hall Clinic
state: Maharashtra
city: Vellore
country: India
facility: Christian Medial College
state: Tamil Nadu
city: Tel-Aviv
country: Israel
facility: Telaviv Sourasky Medical Center, Head and Neck Service Division of Oncology
city: Milano
country: Italy
facility: Lo Studio E la Cura
city: Napoli
country: Italy
facility: INT Napoli Fondazione Pascale
city: Padova
country: Italy
facility: Istituto Oncologico Veneto (IOV) - IRCCS
city: Pisa
country: Italy
facility: Azienda Ospedaliero - Universitaria Pisana
city: Gliwice
country: Poland
facility: Zaklad Medyczny Nuklearnej i Endykrynologii
city: Warszawa
country: Poland
facility: Klinika Nowotworow Glowy i Szyji
city: Cluj-Napoca
country: Romania
facility: Institutul Oncologic
city: Craiova
country: Romania
facility: SC Meditech SRL
city: Iasi
country: Romania
facility: Centr of Medical Oncology
city: Sibiu
country: Romania
facility: Clinical County Hospital Sibiu
city: Suceava
country: Romania
facility: Emergency Clinical County Hospital "Sf. loan cel Nou"
city: Saint Petersburg
country: Russian Federation
facility: City Clinical Oncology Dispensary
city: Lomonosova 33/43
country: Ukraine
facility: Ukrainian Academy of Medical Science
state: Kiev
city: Lvov
country: Ukraine
facility: Regional Clinical Oncology Dispensary
city: Glasgow
country: United Kingdom
facility: Beatson Oncology Centre, Gartnavel General Hospital
state: Scotland
city: London
country: United Kingdom
facility: Royal Marsden Hospital and Institute of Cancer Research
city: Southampton
country: United Kingdom
facility: Southampton Hospital Oncology Centre
Study officials:
affiliation: Yale University School of Medicine, New Haven, CT
name: Julie A. Sosa, MD, FACS
role: PRINCIPAL_INVESTIGATOR
References:
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. doi: 10.1210/jc.2007-0027. Epub 2007 Jun 5.
citation: Patel KN, Shaha AR. Poorly differentiated and anaplastic thyroid cancer. Cancer Control. 2006 Apr;13(2):119-28. doi: 10.1177/107327480601300206.
citation: Ain KB. Anaplastic thyroid carcinoma: behavior, biology, and therapeutic approaches. Thyroid. 1998 Aug;8(8):715-26. doi: 10.1089/thy.1998.8.715.
citation: 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. doi: 10.1016/j.ijrobp.2004.05.032.
citation: Siemann DW, Chaplin DJ, Horsman MR. Vascular-targeting therapies for treatment of malignant disease. Cancer. 2004 Jun 15;100(12):2491-9. doi: 10.1002/cncr.20299.
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. doi: 10.1158/0008-5472.CAN-06-2848.
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.