IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. 
Pembrolizumab, Chemotherapy, and Radiation Therapy With or Without Surgery in Treating Patients With Anaplastic Thyroid Cancer
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
Purpose
| Condition | Intervention | Phase |
|---|---|---|
| Thyroid Gland Undifferentiated (Anaplastic) Carcinoma | Drug: Docetaxel Drug: Doxorubicin Hydrochloride Radiation: Intensity-Modulated Radiation Therapy Other: Laboratory Biomarker Analysis Biological: Pembrolizumab Procedure: Therapeutic Conventional Surgery | Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: No masking Primary Purpose: Treatment |
| Official Title: | Phase 2 Study of Pembrolizumab Combined With Chemoradiation Therapy in Anaplastic Thyroid Cancer |
- Overall survival rate [ Time Frame: At 6 months ]Defined as the proportion of evaluable patients who are alive at 6 months.
- Incidence of adverse events graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 5 years ]The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine adverse event patterns.
- Number of patients with locoregional recurrence and locoregional progression in the thyroid bed or regional lymph nodes [ Time Frame: Up to 5 years ]Will be summarized using descriptive statistics.
- Numbers of patients with distant metastasis [ Time Frame: Up to 5 years ]Will be summarized using descriptive statistics.
| Estimated Enrollment: | 25 |
| Anticipated Study Start Date: | July 9, 2017 |
| Estimated Study Completion Date: | December 9, 2019 |
| Estimated Primary Completion Date: | December 9, 2019 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: 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.
|
Drug: Docetaxel
Given IV
Other Names:
Drug: Doxorubicin Hydrochloride
Given IV
Other Names:
Radiation: Intensity-Modulated Radiation Therapy
Undergo IMRT
Other Names:
Other: Laboratory Biomarker Analysis
Correlative studies
Biological: Pembrolizumab
Given IV
Other Names:
Procedure: Therapeutic Conventional Surgery
Undergo surgery
|
|
Experimental: 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.
|
Drug: Docetaxel
Given IV
Other Names:
Drug: Doxorubicin Hydrochloride
Given IV
Other Names:
Radiation: Intensity-Modulated Radiation Therapy
Undergo IMRT
Other Names:
Other: Laboratory Biomarker Analysis
Correlative studies
Biological: Pembrolizumab
Given IV
Other Names:
|
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.
Eligibility| Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
- Creatinine =< 1.5 x ULN OR calculated creatinine clearance >= 50 ml/min using the Cockcroft-Gault formula
- Prothrombin time (PT)/activated partial thromboplastin time (PTT) =< 1.5 x ULN, unless subject is receiving anticoagulant therapy and PT or activated (a)PTT is within therapeutic range of intended use of anticoagulants
-
Negative pregnancy test done =< 7 days prior to registration, for persons of childbearing potential only
- NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- NOTE: Merck requires an additional pregnancy test if eligibility pregnancy test is > 72 hours prior to first dose
-
Persons of childbearing potential must be willing to use an adequate method of birth control for the course of the study through 120 days after the last dose of study medication
- NOTE: Abstinence is acceptable if this is the usual lifestyle and preferred method of contraception for the patient
-
Persons able to father a child must agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy
- NOTE: Abstinence is acceptable if this is the usual lifestyle and preferred method of contraception for the patient
- Provide written informed consent
- Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
- Willing to provide tissue and blood samples for correlative research purposes
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
- Systemic lupus erythematosus
- Autoimmune hepatitis
- Other autoimmune disease not listed above
- NOTE: Subjects with autoimmune thyroid disease and diabetes mellitus type I will be allowed
-
Uncontrolled intercurrent illness including, but not limited to,
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia, or
- Psychiatric illness/social situations that would limit compliance with study requirements
-
Other active malignancy =< 6 months prior to registration
- EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix or prostate cancer confined to prostate gland with Gleason score < 6 or prostate-specific antigen (PSA) < 1
- NOTE: If there is a history of prior malignancy, they must not be receiving other treatment for their cancer; ongoing adjuvant hormonal treatment for breast cancer is allowed
- Prior known allergic reaction to pembrolizumab or its excipients
- Untreated brain metastasis
- Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy
- Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
- Received any live vaccine =< 30 days prior to registration
-
Any of the following conditions =< 6 weeks prior to registration:
- Cerebrovascular accident (CVA)
- Admission for unstable angina
- Cardiac angioplasty or stenting or coronary artery bypass graft surgery
- Pulmonary embolism or untreated deep venous thrombosis (DVT)
- Arterial thrombosis
- Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system
Contacts and LocationsPlease refer to this study by its ClinicalTrials.gov identifier: NCT03211117
| United States, Minnesota | |
| Mayo Clinic | Not yet recruiting |
| Rochester, Minnesota, United States, 55905 | |
| Contact: Clinical Trials Referral Office 855-776-0015 | |
| Principal Investigator: Ashish V. Chintakuntlawar | |
| Principal Investigator: | Ashish Chintakuntlawar | Mayo Clinic |
More Information
| Responsible Party: | Mayo Clinic |
| ClinicalTrials.gov Identifier: | NCT03211117 History of Changes |
| Other Study ID Numbers: |
MC1679 NCI-2017-01179 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) MC1679 ( Other Identifier: Mayo Clinic ) P30CA015083 ( U.S. NIH Grant/Contract ) |
| Study First Received: | July 6, 2017 |
| Last Updated: | July 6, 2017 |
| Studies a U.S. FDA-regulated Drug Product: | Yes | |
| Studies a U.S. FDA-regulated Device Product: | No | |
Additional relevant MeSH terms:
|
Thyroid Diseases Thyroid Neoplasms Thyroid Carcinoma, Anaplastic Endocrine System Diseases Endocrine Gland Neoplasms Neoplasms by Site Neoplasms Head and Neck Neoplasms Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Doxorubicin |
Liposomal doxorubicin Docetaxel Pembrolizumab Antibiotics, Antineoplastic Antineoplastic Agents Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Tubulin Modulators Antimitotic Agents Mitosis Modulators |
ClinicalTrials.gov processed this record on July 11, 2017