Thyroid Gland Undifferentiated (Anaplastic) Carcinoma Clinical Trial
Official title:
Phase 2 Study of Pembrolizumab Combined With Chemoradiation Therapy in Anaplastic Thyroid Cancer
This phase II trial studies how well pembrolizumab, chemotherapy, and radiation therapy work with or without surgery in treating patients with anaplastic thyroid cancer. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as docetaxel and doxorubicin hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Giving pembrolizumab, chemotherapy, and radiation therapy with or without surgery may kill more tumor cells and work better in treating patients with anaplastic thyroid cancer.
PRIMARY OBJECTIVES:
I. To assess the efficacy of pembrolizumab in improving overall survival at 6 months (OS-6)
in combination with multimodal therapy involving standard chemo-radiotherapy in anaplastic
thyroid cancer (ATC) in comparison to a historical cohort.
SECONDARY OBJECTIVES:
I. To determine safety and tolerance of pembrolizumab with chemoradiotherapy.
TERTIARY OBJECTIVES:
I. To evaluate locoregional control. II. To evaluate progression of distant metastases. III.
To evaluate the evolution of the immune profile of circulating immune cells in response to
therapy in ATC patents, and to assess potential correlations with outcomes on an exploratory
basis.
IV. To evaluate PD-1 and PD-L1 staining in tumor cells and tumor stroma as candidate
biomarkers for outcomes.
V. To determine if pre-therapy circulating tumor cell load is associated with outcomes.
VI. To examine associations between outcomes and somatic mutational status as assessed by
foundation medicine analysis (for example: presence of BRAF, RAS, P53 and TERT promoter
mutations).
OUTLINE: Patients are assigned to 1 of 2 cohorts.
COHORT A: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1.
Treatment with pembrolizumab repeats every 21 days for up to 17 courses after chemoradiation
if no residual disease is found or for up to 35 courses after chemoradiation if residual
disease is found. After 3 days, patients undergo surgery. Within 42 days of surgery, patients
also receive docetaxel IV over 1 hour once weekly (Q1W) and doxorubicin hydrochloride IV Q1W,
and undergo intensity-modulated radiation therapy (IMRT) once daily 5 days per week for 6.5
weeks in the absence of disease progression or unacceptable toxicity.
COHORT B: Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment with
pembrolizumab repeats every 21 days for up to 17 courses after chemoradiation if no residual
disease is found or for up to 35 courses after chemoradiation if residual disease is found.
After 3 days, patients also receive docetaxel IV over 1 hour Q1W and doxorubicin
hydrochloride IV Q1W, and undergo IMRT once daily 5 days per week for 6.5 weeks in the
absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months until
progressive disease and then every 6 months for up to 5 years.
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