COMBRETASTATIN/DOXORUBICIN/CISPLATIN FOR PATIENTS WITH THYROID CANCER

点击翻译按钮获取中文摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This investigator-initiated study is based on preclinical data and previous Phase I clinical experience in patients with thyroid cancer who were treated with Combretastatin A-4 Phosphate (CA4P). Results from those studies suggest that CA4P is suitable for further clinical development in the Phase II setting as part of combined modality treatment for anaplastic thyroid cancer with the potential to define a new standard of care for these patients. The objectives of the study are: 1) to determine the objective response rate of CA4P-based combined modality therapy (with concurrent radiation and consolidation treatment) given to patients with newly diagnosed regionally advanced anaplastic carcinoma of the thyroid; 2) to determine whether CA4P-based combined modality therapy alters the natural history of anaplastic thyroid cancer by virtue of doubling the median survival of these patients from 10 months to 20 months; 3) to further characterize a tolerable dose and the safety profile of CA4P when administered as part of a combined modality regimen; and 4) to determine clinical predictors of response to CA4P-based combined modality therapy by analysis of several measures including pharmacokinetics. This study plans to enroll up to 33 subjects (with up to 27 subjects at this site). The study is separated into three phases: Induction Phase, Combined Modality Phase (with dose escalation of CA4P), and Consolidation Phase. During the Induction Phase, subjects will receive initial combination chemotherapy for 1 cycle (3 weeks) (doxorubicin + cisplatin + G-CSF (granulocyte-colony stimulating factor) or neulasta). In the Combined Modality Phase, subjects will receive CA4P and radiation therapy for 4 weeks and then spend 4-6 weeks recovering. In the Consolidation Phase, CA4P will be administered for two 4-week cycles. Study monitoring will include vital signs, EKGs and pharmacokinetic sampling.