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

This study has been terminated.
(inadequate funding)
Sponsor:
Information provided by (Responsible Party):
OXiGENE
ClinicalTrials.gov Identifier:
NCT00507429
First received: July 25, 2007
Last updated: January 17, 2012
Last verified: October 2011
  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: combretastatin A-4 phosphate (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

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 evaluate safety based on frequency and severity of adverse events [ Time Frame: from first dose of study drug through 30 days after last dose of study drug ] [ Designated as safety issue: Yes ]
  • To assess number of tracheostomies [ Time Frame: from randomization through end of study visit ] [ Designated as safety issue: Yes ]
  • To assess number of PEG tube placements [ Time Frame: from randomization through end of study visit ] [ Designated as safety issue: No ]
  • To assess weight loss [ Time Frame: from randomization through end of study visit ] [ Designated as safety issue: No ]
  • 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: July 2007
Study Completion Date: November 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
CA4P + carboplatin + paclitaxel
Drug: combretastatin A-4 phosphate (CA4P)
CA4P 60mg/m squared for Days 1, 8, 15 for 6 cycles
Other Names:
  • combretastatin
  • Zybrestat
Active Comparator: 2
Carboplatin + paclitaxel
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:

  • 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00507429

  Show 41 Study Locations
Sponsors and Collaborators
OXiGENE
  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
Last Updated: January 17, 2012
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
Paclitaxel
Combretastatin A-4
Carboplatin
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 22, 2014