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

Tracking Information

Start Date  ICMJEJuly 2007
Estimated Primary Completion DateDecember 2010   (final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE 
 (submitted: January 25, 2008)
Overall survival [ Time Frame: one year ] [ Designated as safety issue: Yes ]
Original Primary Outcome Measures  ICMJE 
 (submitted: July 25, 2007)
Overall survival
Change HistoryComplete list of historical versions of study NCT00507429 on Archive Site
Current Secondary Outcome Measures  ICMJE 
 (submitted: January 25, 2008)
To evaluate the safety and tolerability of the triplet combretastatin+paclitaxel+carboplatin combination [ Time Frame: one year ] [ Designated as safety issue: Yes ]
Original Secondary Outcome Measures  ICMJE 
 (submitted: July 25, 2007)
To evaluate the safety and tolerability of the triplet combretastatin+paclitaxel+carboplatin combination

Descriptive Information

Brief Title  ICMJEStudy of Combretastatin and Paclitaxel/Carboplatin in the Treatment of Anaplastic Thyroid Cancer
Official Title  ICMJEA 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
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.

Study PhasePhase II, Phase III
Study Type  ICMJEInterventional
Study Design  ICMJETreatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Condition  ICMJEAnaplastic Thyroid Cancer
Intervention  ICMJE
  • Drug: combretastatin A-4 phosphate (CA4P)
    CA4P 60mg/m squared for Days 1, 8, 15 for 6 cycles
    Other Names:
    • combretastatin
    • Zybrestat
  • Drug: paclitaxel
    200mg/m squared on Day 1
    Other Names:
    • Taxol
    • Paxene
  • Drug: carboplatin
    6 AUC on Day 1 following paclitaxel
    Other Name: Paraplatin
Study Arms / Comparison Groups
  • 1: Experimental
    CA4P + carboplatin + paclitaxel
    Intervention: Drug: combretastatin A-4 phosphate (CA4P)
  • 2: Active Comparator
    Paclitaxel 200mg/m squared on DAy 1 followed by carboplatin 6 AUC on Day 1 for 6 cycles
    • Drug: paclitaxel
    • Drug: carboplatin
Publications *

Recruitment Information

Estimated Enrollment  ICMJE180
Completion Date 
Estimated Primary Completion DateDecember 2010   (final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients must have anaplastic thyroid carcinoma histologically or cytologically confirmed by a pathology review.
  • 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.
  • 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.
  • In patients having received prior radiation, 3 weeks must have elapsed since radiation and disease must be present beyond radiation ports.
  • 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 weeks for therapy known to be associated with delayed toxicity such as nitrosureas or mitomycin-C).
  • 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.
  • Patients must be greater than or equal to 18 years of age.
  • Patients must have an Eastern Cooperative Oncology Group (ECOG) Performance Score less than or equal to 2.
  • Life expectancy greater than or equal to 12 weeks.
  • Patients must have adequate bone marrow reserve as evidenced by:

Absolute neutrophil count (ANC) greater than 1,500/microL. Platelet count greater than 75,000/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).
  • 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).

  • Patients or their legal representatives must be able to read, understand and provide written informed consent to participate in the trial.
  • Patients must have no clinically important sequelae from any prior surgery or radiotherapy.
  • All women of childbearing potential must have a negative serum pregnancy test.
  • 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:

  • Patients with tumors confined to the thyroid.
  • Patients with an uncontrolled active infection.
  • 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.
  • 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.)
  • Patients with known hypersensitivity to CA4P, paclitaxel or carboplatin, or any of their components.
  • 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.)
  • Patients with greater than Grade 2 peripheral neuropathy.
  • Patients who are pregnant or lactating.
  • Patients with a history of prior cerebrovascular event, including transient ischemic attack.
  • Patients with uncontrolled hypertension defined as blood pressure greater than 150/100 mm Hg despite medication.
  • Patients with symptomatic vascular disease (e.g. intermittent claudication)
  • 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.
  • Patients with a history of torsade de pointes.
  • Patients with bradycardia (less than 60 b/m), heart block (excluding 1st degree block, being PR interval prolongation only), and congenital long QT syndrome.
  • Patients with any ventricular arrhythmias, or new ST segment elevation or depression or Q wave on ECG.
  • Patients with ejection fractions less than normal (i.e. less than 45%).
  • Patients with QTc prolongation greater than 450 ms.
  • Patients requiring any drugs known to prolong the QTc interval, including anti-arrhythmic medications.
  • Patients with potassium concentrations below 4.0 mEq/dL and magnesium concentrations below 1.8 mg/dL despite being on an electrolyte supplement.
  • Patients requiring any drugs known to prolong the QTc interval.
  • 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.
  • Patients with a history of solid organ transplant or bone marrow transplant.
Ages18 Years and older
Accepts Healthy VolunteersNo
Contacts  ICMJE 
Location Countries  ICMJEUnited States,   Belarus,   Bulgaria,   Egypt,   India,   Israel,   Italy,   Poland,   Romania,   Russian Federation,   Ukraine,   United Kingdom

Administrative Information

Responsible PartyPeter Langecker / CDO, Oxigene, Inc.
Study ID Numbers  ICMJEOXC4T4-302
Study Sponsor  ICMJEOXiGENE
Collaborators  ICMJE 
Investigators  ICMJE 
Information Provided ByOXiGENE