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]
- 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
- 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.
- 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
Patients are followed every 2 months for 1 year and then every 3 months for 2 years from
PROJECTED ACCRUAL: A total of 33 patients will be accrued for this study within 18 months.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
at months 2, 4, 6, 8, 10, 12, 15, 18, 21, 24, 27, 30, 33, and 36
Panayiotis Savvides, MD
Ireland Cancer Center at University Hosptials Case Medical Center, Case Comprehensive Cancer Center
United States: Federal Government
|Hillman Cancer Center at University of Pittsburgh Cancer Institute||Pittsburgh, Pennsylvania 15236|
|Josephine Ford Cancer Center at Henry Ford Hospital||Detroit, Michigan 48202|
|Ireland Cancer Center at University Hosptials Case Medical Center, Case Comprehensive Cancer Center||Cleveland, Ohio 44106-5065|