- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00077103
Induction Chemotherapy Using Doxorubicin and Cisplatin Followed by Combretastatin A4 Phosphate and Radiation Therapy in Treating Patients With Newly Diagnosed Regionally Advanced Anaplastic Thyroid Cancer
Phase II Trial of Combined Modality Combretastatin A-4 Phosphate (CA4P)-Based Therapy for Patients With Newly Diagnosed Anaplastic Thyroid Cancer [Induction Chemotherapy With Doxorubicin/Cisplatin; Combined Modality Therapy With CA4P and Radiation; Followed by 2 Cycles of CA4P Consolidation]
RATIONALE: Drugs used in chemotherapy, such as doxorubicin and cisplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combretastatin A4 phosphate may stop the growth of cancer by stopping blood flow to the tumor. Combining doxorubicin and cisplatin with radiation therapy and combretastatin A4 phosphate may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving induction chemotherapy using doxorubicin and cisplatin together with radiation therapy and combretastatin A4 phosphate works in treating patients with newly diagnosed regionally advanced anaplastic thyroid cancer.
Study Overview
Status
Conditions
Detailed Description
OBJECTIVES:
Primary
- Determine the objective response rate in patients with newly diagnosed regionally advanced anaplastic thyroid cancer treated with induction chemotherapy comprising doxorubicin and cisplatin followed by combretastatin A4 phosphate (CA4P) and radiotherapy.
- Determine whether this regimen alters the natural history of anaplastic thyroid cancer by virtue of doubling the median survival of these patients from 10 to 20 months.
Secondary
- Determine a tolerable dose of CA4P when administered with radiotherapy in these patients. (Phase I portion of the study closed as of 5/6/04; patients now receive a fixed dose of CA4P)
- Determine the safety profile of this regimen in these patients.
- Determine clinical predictors of response (e.g., pretreatment tumor microvessel density and immature vessel staining, changes in sICAM-1 levels and tumor blood flow, and pharmacokinetic parameters) in patients treated with this regimen.
- Correlate the diminution in blood flow with tumor pain and response in patients treated with this regimen.
OUTLINE: This is a multicenter study of combretastatin A4 phosphate (CA4P). (Phase I portion of the study closed as of 5/6/04; patients now receive a fixed dose of CA4P)
- Induction phase: Patients receive doxorubicin IV over 5-10 minutes and cisplatin IV over 30-60 minutes on day 1. Patients also receive filgrastim (G-CSF) subcutaneously (SC) on days 3-21 or pegfilgrastim SC on day 2.
- Combined modality phase: Beginning on day 22, patients undergo radiotherapy twice daily, 5 days a week, for 3-4 weeks. Patients also receive CA4P IV over 10 minutes weekly on the fifth day of radiotherapy.
Cohorts of 6 patients receive 1 of 2 escalating doses of CA4P to determine a tolerable dose. The tolerable dose is defined as the dose at which less than 2 of 6 patients experience dose-limiting toxicity. (Phase I portion of the study closed as of 5/6/04; patients now receive a fixed dose of CA4P)
- Consolidation phase: Beginning 4-6 weeks after the completion of the combined modality phase, patients receive CA4P IV over 10 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 2 courses.
Treatment in all phases continues in the absence of disease progression or unacceptable toxicity.
Patients are followed every 2 months for 1 year and then every 3 months for 2 years from study entry.
PROJECTED ACCRUAL: A total of 33 patients will be accrued for this study within 18 months.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
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
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Pittsburgh, Pennsylvania, United States, 15232
- Hillman Cancer Center at University of Pittsburgh Cancer Institute
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
DISEASE CHARACTERISTICS:
Histologically confirmed anaplastic or poorly differentiated variant thyroid carcinoma of either of the following:
Regionally advanced disease
- Confined to the neck and/or superior mediastinum (i.e., above the level of the carina)
- Measurable or evaluable* disease
- Completely resected disease without measurable or evaluable disease NOTE: *At a minimum, abnormalities on physical exam or radiographic studies that may not be precisely measured but readily followed
Must have original/diagnostic tumor blocks available to confirm histopathology and for tumor microvessel density immunohistochemistry
- Patients with no available original/diagnostic tumor blocks must have tumor accessible for pretreatment needle core biopsy
- Must undergo indirect and direct laryngoscopy to ensure patency of the trachea/airway if deemed inoperable, with bulky thyroid/neck masses and/or suspicion of airway obstruction
No distant metastases, including but not limited to, brain metastases, disease below the level of the carina, pulmonary parenchyma, and hepatic or bony metastases
- Superior mediastinal disease (i.e., above the level of the carina) in addition to regional neck disease is allowed provided the disease can be contained in a single radiotherapy port
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- ECOG 0-2
Life expectancy
- At least 12 weeks
Hematopoietic
- Absolute granulocyte count ≥ 1,500/mm^3
- Platelet count ≥ 75,000/mm^3
- Hemoglobin ≥ 8.5 g/dL
Hepatic
- Bilirubin ≤ 1.5 mg/dL
- ALT and AST ≤ 3.5 times upper limit of normal
Renal
- Creatinine ≤ 1.5 mg/dL
Cardiovascular
- LVEF ≥ 50% by echocardiogram
- EKG normal
- No prior angina
- No prior myocardial infarction (e.g., significant Q waves), QTc > 450 msec, or other clinically significant abnormalities on ECG
- No congestive heart failure
No uncontrolled atrial arrhythmias or clinically significant arrhythmias, including any of the following:
- Conduction abnormality
- 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 echocardiogram
No uncontrolled hypertension (i.e., blood pressure consistently greater than 150/100 mm Hg irrespective of medication)
- Hypertension is allowed provided there is clinical documentation of controlled blood pressure for 2 months before study entry
- No symptomatic peripheral vascular disease or cerebrovascular disease
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No uncontrolled hypokalemia or hypomagnesemia
- No concurrent serious infection
- No other nonmalignant uncontrolled medical illness or one whose control may be jeopardized by the complications of study therapy
- No grade 2 or greater pre-existing motor or sensory peripheral neuropathy
- No psychiatric disorder or other condition that would preclude study compliance
- No conditions associated with QTc prolongation
PRIOR CONCURRENT THERAPY:
Biologic therapy
- No concurrent biologic therapy
- No concurrent immunotherapy
Chemotherapy
- No prior chemotherapy
- No other concurrent chemotherapy
Endocrine therapy
No concurrent hormonal therapy, except for the following:
- Gonadotropin-releasing hormone agonists for patients with hormone-refractory prostate cancer
- Hormone replacement therapy
- Oral contraceptives
- Megestrol for anorexia/cachexia
Radiotherapy
- No prior radiotherapy
- No concurrent radiotherapy
Surgery
- See Disease Characteristics
- Prior attempt at resection or cytoreduction (e.g., debulking) surgery irrespective of surgical margins allowed provided there are no distant metastases
- At least 1 week but no more than 8 weeks since prior surgery and recovered
Other
- No other concurrent cytotoxic therapy
- No other concurrent antineoplastic therapy
- No other concurrent investigational therapy
- No concurrent medications known to prolong the QTc interval unless the medication can be held for at least 4 days during each treatment course
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Median survival
Time Frame: at months 2, 4, 6, 8, 10, 12, 15, 18, 21, 24, 27, 30, 33, and 36
|
at months 2, 4, 6, 8, 10, 12, 15, 18, 21, 24, 27, 30, 33, and 36
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Objective disease response
Time Frame: at the end of induction, combined modality therapy, and consolidation therapy, at 2 months after completion of consolidation therapy, at 2 month intervals during year 1, and then 3 month intervals during years 2 and 3
|
at the end of induction, combined modality therapy, and consolidation therapy, at 2 months after completion of consolidation therapy, at 2 month intervals during year 1, and then 3 month intervals during years 2 and 3
|
Collaborators and Investigators
Sponsor
Collaborators
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Endocrine System Diseases
- Endocrine Gland Neoplasms
- Thyroid Diseases
- Head and Neck Neoplasms
- Thyroid Neoplasms
- Thyroid Carcinoma, Anaplastic
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antineoplastic Agents, Phytogenic
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Antibiotics, Antineoplastic
- Doxorubicin
- Liposomal doxorubicin
- Fosbretabulin
- Combretastatin
Other Study ID Numbers
- CWRU3302
- P30CA043703 (U.S. NIH Grant/Contract)
- CASE-CWRU-3302 (Other Identifier: Case Comprehensive Cancer Center)
- CWRU-040337
- OXIGENE-CWRU-3302
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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