Phase 2 Study of Pembrolizumab Combined With Chemoradiation Therapy in Anaplastic Thyroid Cancer
Overview
- Phase
- Phase 2
- Intervention
- Docetaxel
- Conditions
- Thyroid Gland Undifferentiated (Anaplastic) Carcinoma
- Sponsor
- Mayo Clinic
- Enrollment
- 3
- Locations
- 1
- Primary Endpoint
- Overall Survival Rate
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histological confirmation of, or cytology reported and confirmed, anaplastic thyroid cancer
- •NOTE: A diagnosis reported as ?poorly differentiated carcinoma consistent with anaplastic thyroid cancer? will be accepted
- •Absence of prior neck radiotherapy
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
- •Hemoglobin \>= 9.0 g/dL
- •White blood cells (WBC)/leukocytes \>= 3500/mm\^3
- •Absolute neutrophil count (ANC) \>= 1500/mm\^3
- •Platelet count \>= 100,000/mm\^3
- •Total bilirubin =\< 1.5 x upper limit of normal (ULN) (except for patients with well-documented Gilbert?s syndrome)
- •Aspartate transaminase (AST) =\< 3 x ULN
Exclusion Criteria
- •History of non-infectious pneumonitis that required steroids or current pneumonitis
- •Any of the following:
- •Pregnant persons
- •Nursing persons
- •Persons of childbearing potential who are unwilling to employ adequate contraception
- •Any autoimmune disease such as inflammatory bowel disease, including but not limited to:
- •Ulcerative colitis
- •Crohn's disease
- •Rheumatoid arthritis
- •Systemic sclerosis
Arms & Interventions
Cohort A (pembrolizumab, surgery, chemoradiation)
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 undergo surgery. Within 42 days of surgery, 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.
Intervention: Docetaxel
Cohort A (pembrolizumab, surgery, chemoradiation)
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 undergo surgery. Within 42 days of surgery, 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.
Intervention: Doxorubicin Hydrochloride
Cohort A (pembrolizumab, surgery, chemoradiation)
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 undergo surgery. Within 42 days of surgery, 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.
Intervention: Intensity-Modulated Radiation Therapy
Cohort A (pembrolizumab, surgery, chemoradiation)
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 undergo surgery. Within 42 days of surgery, 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.
Intervention: Laboratory Biomarker Analysis
Cohort A (pembrolizumab, surgery, chemoradiation)
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 undergo surgery. Within 42 days of surgery, 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.
Intervention: Pembrolizumab
Cohort A (pembrolizumab, surgery, chemoradiation)
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 undergo surgery. Within 42 days of surgery, 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.
Intervention: Therapeutic Conventional Surgery
Cohort B (pembrolizumab, chemoradiation)
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.
Intervention: Docetaxel
Cohort B (pembrolizumab, chemoradiation)
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.
Intervention: Doxorubicin Hydrochloride
Cohort B (pembrolizumab, chemoradiation)
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.
Intervention: Intensity-Modulated Radiation Therapy
Cohort B (pembrolizumab, chemoradiation)
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.
Intervention: Laboratory Biomarker Analysis
Cohort B (pembrolizumab, chemoradiation)
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.
Intervention: Pembrolizumab
Outcomes
Primary Outcomes
Overall Survival Rate
Time Frame: At 6 months
Defined as the percentage of evaluable patients who are alive at 6 months.
Secondary Outcomes
- Incidence of Adverse Events Graded Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0(2.3 years)