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

This study has been terminated.
(Low rate of subject accrual)
Sponsor:
Information provided by (Responsible Party):
OXiGENE
ClinicalTrials.gov Identifier:
NCT00507429
First received: July 25, 2007
Last updated: May 12, 2014
Last verified: February 2014
  Purpose

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).


Condition Intervention Phase
Anaplastic Thyroid Cancer
Drug: CA4P
Drug: paclitaxel
Drug: carboplatin
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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]

Resource links provided by NLM:


Further study details as provided by OXiGENE:

Primary Outcome Measures:
  • Overall Survival [ Time Frame: From randomization to date last known alive ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To Determine Progression Free Survival [ Time Frame: from randomization through end of study visit ] [ Designated as safety issue: No ]
  • To Determine Percentage of 1 Year Survival [ Time Frame: from randomization through end of study visit ] [ Designated as safety issue: No ]

Enrollment: 80
Study Start Date: August 2007
Study Completion Date: November 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1: CA4P + Carboplatin + paclitaxel
Six 21-day cycles: CA4P (60 mg/m2 on Days 1, 8, 15), carboplatin (AUC 6) + paclitaxel (200 mg/m2) on Day 2
Drug: CA4P
CA4P 60mg/m squared for Days 1, 8, 15 for 6 cycles
Other Names:
  • combretastatin
  • fosbretabulin
  • Zybrestat
Active Comparator: Arm 2: Carboplatin + Paclitaxel
Six 21-day cycles of Carboplatin (AUC 6) + paclitaxel (200 mg/m2) given on Day 1
Drug: paclitaxel
200mg/m squared on Day 1
Other Names:
  • Taxol
  • Paxene
Drug: carboplatin
6 AUC on Day 1 following paclitaxel
Other Name: Paraplatin

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00507429

  Show 41 Study Locations
Sponsors and Collaborators
OXiGENE
Investigators
Principal Investigator: Julie A. Sosa, MD, FACS Yale University School of Medicine, New Haven, CT
  More Information

Additional Information:
Publications:
Responsible Party: OXiGENE
ClinicalTrials.gov Identifier: NCT00507429     History of Changes
Other Study ID Numbers: OXC4T4-302
Study First Received: July 25, 2007
Results First Received: August 16, 2013
Last Updated: May 12, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by OXiGENE:
thyroid neoplasms
thyroid cancer
thyroid carcinoma

Additional relevant MeSH terms:
Thyroid Neoplasms
Thyroid Diseases
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Endocrine System Diseases
Combretastatin
Fosbretabulin
Paclitaxel
Carboplatin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 19, 2014