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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

Phase 2/Phase 3
18 Years
Not Enrolling
Anaplastic Thyroid Cancer

Thank you

Trial Information

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

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.

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

- 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

- 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

- 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

- 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.

Type of Study:


Study Design:

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

Outcome Measure:

Overall survival

Outcome Time Frame:

from randomization to date last known alive

Safety Issue:



United States: Food and Drug Administration

Study ID:




Start Date:

July 2007

Completion Date:

November 2011

Related Keywords:

  • Anaplastic Thyroid Cancer
  • thyroid neoplasms
  • thyroid cancer
  • thyroid carcinoma
  • Thyroid Neoplasms
  • Thyroid Diseases



USC/Norris Comprehensive Cancer CenterLos Angeles, California  90033-0800
University of Colorado Cancer CenterDenver, Colorado  80262
University of Texas M.D. Anderson Cancer CenterHouston, Texas  77030
Oregon Health and Science UniversityPortland, Oregon  97201
West Virginia UniversityMorgantown, West Virginia  26506
Winship Cancer Institute, Emory UniversityAtlanta, Georgia  30322
Yale University, School of MedicineNew Haven, Connecticut  06520
Sidney Kimmel Comprehensive Cancer Care Center at John HopkinsBaltimore, Maryland  21231
University of Minnesota Otolaryngology DepartmentMinneapolis, Minnesota  55455
Ireland Cancer Center/Division od HematologyCleveland, Ohio  44106