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

NCT00077103 | Terminated Phase 1 DMC

• 5 other identifiers: CWRU3302P30CA043703CASE-CWRU-3302CWRU-040337OXIGENE-CWRU-3302
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Head and Neck Cancer

Keywords

anaplastic thyroid cancer

Outcome Measures

Primary Outcomes (1)

• Median survival

  at months 2, 4, 6, 8, 10, 12, 15, 18, 21, 24, 27, 30, 33, and 36

Secondary Outcomes (1)

• Objective disease response

  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

Interventions

filgrastim BIOLOGICAL

filgrastim (G-CSF) subcutaneously (SC) on days 3-21 or pegfilgrastim SC on day 2.

pegfilgrastim BIOLOGICAL

filgrastim (G-CSF) subcutaneously (SC) on days 3-21 or pegfilgrastim SC on day 2.

cisplatin DRUG

cisplatin IV over 30-60 minutes on day 1

doxorubicin hydrochloride DRUG

doxorubicin IV over 5-10 minutes

fosbretabulin disodium DRUG

Combined Modality Phase:Patients also receive CA4P IV over 10 minutes weekly on the fifth day of radiotherapy. 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.

Also known as: Combretastatin A-4 Phosphate, CA4P

radiation therapy RADIATION

Beginning on day 22, patients undergo radiotherapy twice daily, 5 days a week, for 3-4 weeks.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Josephine Ford Cancer Center at Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Ireland Cancer Center at University Hosptials Case Medical Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106-5065, United States

Location

Hillman Cancer Center at University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Head and Neck Neoplasms; Thyroid Carcinoma, Anaplastic

Interventions

Filgrastim; pegfilgrastim; Cisplatin; Doxorubicin; fosbretabulin; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Therapeutics

Study Officials

• Panayiotis Savvides, MD

  Ireland Cancer Center at University Hosptials Case Medical Center, Case Comprehensive Cancer Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: February 10, 2004
• First Posted: February 11, 2004
• Study Start: November 1, 2003
• Primary Completion: February 1, 2007
• Study Completion: December 1, 2007
• Last Updated: June 11, 2010

Record last verified: 2010-06

Locations

US (3)