Combretastatin A4 Phosphate in Treating Patients With Advanced Anaplastic Thyroid Cancer

NCT00060242 | Completed Phase 2 DMC

• 3 other identifiers: ICC2302P30CA043703CASE-CWRU-ICC-2302
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 3

Brief Summary

RATIONALE: Combretastatin A4 phosphate may stop the growth of anaplastic thyroid cancer by stopping blood flow to the tumor. PURPOSE: This phase II trial is studying how well combretastatin A4 phosphate works in treating patients with advanced recurrent or metastatic anaplastic thyroid cancer.

Conditions

Head and Neck Cancer

Keywords

anaplastic thyroid cancer; recurrent thyroid cancer

Outcome Measures

Primary Outcomes (1)

• Median survival

  every 8 weeks

Secondary Outcomes (1)

• Objective disease response

  every 8 weeks

Interventions

fosbretabulin disodium DRUG

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.

Also known as: Combretastatin A4 phosphate

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 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

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

Related Publications (2)

• 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.

  PMID: 19265494 RESULT

• Giri P, Batra PJ, Kumari A, Hura N, Adhikary R, Acharya A, Guchhait SK, Panda D. Development of QTMP: A promising anticancer agent through NP-Privileged Motif-Driven structural modulation. Bioorg Med Chem. 2023 Nov 15;95:117489. doi: 10.1016/j.bmc.2023.117489. Epub 2023 Oct 5.

  PMID: 37816266 DERIVED

MeSH Terms

Conditions

Head and Neck Neoplasms; Thyroid Carcinoma, Anaplastic; Thyroid Neoplasms

Interventions

fosbretabulin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Endocrine Gland Neoplasms; Endocrine System Diseases; Thyroid Diseases

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 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: May 6, 2003
• First Posted: May 7, 2003
• Study Start: February 1, 2003
• Primary Completion: February 1, 2007
• Study Completion: January 1, 2008
• Last Updated: June 11, 2010

Record last verified: 2010-06

Locations

US (3)