Fosbretabulin disodium in Head and Neck Cancer - Clinical Trials Registry

Study Overview

Status

Completed

Conditions

Head and Neck Cancer

Intervention / Treatment

Drug: fosbretabulin disodium

Detailed Description

OBJECTIVES:

Determine the objective response rate of patients with advanced anaplastic thyroid cancer treated with combretastatin A4 phosphate.
Determine whether this drug alters the natural history of anaplastic thyroid cancer, in terms of doubling the median survival from 4-6 months to 12 months, in these patients.
Determine the safety profile of this drug in these patients.
Correlate clinical response with pretreatment tumor microvessel density and immature vessel staining, changes in sICAM-1 levels over the course of treatment, and pharmacokinetic parameters in patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive combretastatin A4 phosphate IV over 10 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) receive 2 courses beyond documentation of the CR.

Patients are followed monthly.

PROJECTED ACCRUAL: A total of 32 patients will be accrued for this study within 18-24 months.

Study Type

Interventional

Enrollment (Actual)

26

Phase

Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

United States
- Michigan
  - Detroit, Michigan, United States, 48202
    - Josephine Ford Cancer Center at Henry Ford Hospital
- Ohio
  - Cleveland, Ohio, United States, 44106-5065
    - Ireland Cancer Center at University Hosptials Case Medical Center, Case Comprehensive Cancer Center
- Pennsylvania
  - Pittsburgh, Pennsylvania, United States, 15232
    - Hillman Cancer Center at University of Pittsburgh Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

Histologically confirmed* anaplastic or poorly differentiated variant thyroid cancer, including 1 of the following:
- Recurrent/regionally advanced disease no longer amenable to definitive curative surgery or radiotherapy
- Untreated metastatic disease NOTE: *If original/diagnostic tumor blocks are unavailable, tumor must be accessible for pretreatment core needle biopsy
Must have relapsed or progressed during or after prior combined modality therapy (e.g., systemic chemotherapy and radiotherapy) for regionally advanced (but not metastatic) disease
Measurable or evaluable disease
Patent trachea and airway by screening direct and indirect laryngoscopy* NOTE: *For patients with bulky thyroid/neck masses and/or suspected airway obstruction
No active brain metastases, as evidenced by any of the following:
- Symptomatic involvement
- Cerebral edema by CT scan or MRI
- Radiographic evidence of progression since definitive therapy
- Continued requirement for corticosteroids

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

ECOG 0-2

Life expectancy

At least 12 weeks

Hematopoietic

Absolute granulocyte count at least 1,500/mm^3
Platelet count at least 75,000/mm^3
Hemoglobin at least 8.5 g/dL

Hepatic

Bilirubin no greater than 1.5 times upper limit of normal (ULN)
ALT and AST no greater than 3.5 times ULN

Renal

Creatinine no greater than 1.5 times ULN

Cardiovascular

LVEF at least 50% by MUGA
EKG normal
- No evidence of prior myocardial infarction (e.g., significant Q waves), QTc greater than 450 msec, or other clinically significant abnormalities
No history of angina (even if controlled by medication)
No congestive heart failure
No uncontrolled atrial arrhythmias
No clinically significant arrhythmias, including any of the following:
- Conduction abnormalities
- Nodal junctional arrhythmias and dysrhythmias
- Sinus bradycardia or tachycardia
- Supraventricular arrhythmias
- Atrial fibrillation or flutter
- Syncope or vasovagal episodes
No significant heart wall abnormality or heart muscle damage by MUGA
No uncontrolled hypertension (blood pressure consistently greater than 150 mm Hg systolic and 100 mm Hg diastolic regardless of medication)
- Patients with previous hypertension are allowed provided there is clinical documentation of controlled blood pressure for 2 months prior to study enrollment
No symptomatic peripheral vascular disease
No symptomatic cerebrovascular disease

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No grade 2 or greater preexisting motor or sensory peripheral neuropathy
No uncontrolled hypokalemia or hypomagnesemia
No concurrent serious infection
No other nonmalignant medical illness that is uncontrolled or whose control may be jeopardized by study therapy
No psychiatric disorders or other conditions that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

No concurrent biologic therapy
No concurrent immunotherapy
No concurrent prophylactic colony-stimulating factors (e.g., filgrastim [G-CSF] or sargramostim [GM-CSF])

Chemotherapy

See Disease Characteristics
At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
No other concurrent chemotherapy

Endocrine therapy

See Disease Characteristics
No concurrent hormonal therapy, except any of the following:
- Gonadotropin-releasing hormone agonists for hormone-refractory prostate cancer
- Hormone replacement therapy
- Oral contraceptives
- Megestrol for anorexia/cachexia

Radiotherapy

See Disease Characteristics
More than 4 weeks since prior radiotherapy with progressive disease beyond radiation ports
No prior radiotherapy to more than 30% of the bone marrow
No concurrent radiotherapy

Surgery

See Disease Characteristics
More than 4 weeks since prior major surgery

Other

At least 6 weeks since other prior therapy associated with delayed toxicity
No prior therapy for metastatic disease
No concurrent medication(s) known to prolong the QTc interval, unless medication(s) can be held for at least 72 hours before, during, and for at least 6 hours after study drug administration
No other concurrent investigational therapy
No other concurrent antineoplastic or cytotoxic therapy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: TREATMENT
Allocation: NA
Interventional Model: SINGLE_GROUP
Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Median survival Time Frame: every 8 weeks	every 8 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Objective disease response Time Frame: every 8 weeks	every 8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Case Comprehensive Cancer Center

Collaborators

National Cancer Institute (NCI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Mooney CJ, Nagaiah G, Fu P, Wasman JK, Cooney MM, Savvides PS, Bokar JA, Dowlati A, Wang D, Agarwala SS, Flick SM, Hartman PH, Ortiz JD, Lavertu PN, Remick SC. A phase II trial of fosbretabulin in advanced anaplastic thyroid carcinoma and correlation of baseline serum-soluble intracellular adhesion molecule-1 with outcome. Thyroid. 2009 Mar;19(3):233-40. doi: 10.1089/thy.2008.0321.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2003

Primary Completion (ACTUAL)

February 1, 2007

Study Completion (ACTUAL)

January 1, 2008

Study Registration Dates

First Submitted

May 6, 2003

First Submitted That Met QC Criteria