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Pembrolizumab, Chemotherapy, and Radiation Therapy With or Without Surgery in Treating Patients With Anaplastic Thyroid Cancer

Primary Purpose

Thyroid Gland Undifferentiated (Anaplastic) Carcinoma

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Docetaxel

Doxorubicin Hydrochloride

Intensity-Modulated Radiation Therapy

Laboratory Biomarker Analysis

Pembrolizumab

Therapeutic Conventional Surgery

About this trial

This is an interventional treatment trial for Thyroid Gland Undifferentiated (Anaplastic) Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Mayo Clinic

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Cohort A (pembrolizumab, surgery, chemoradiation)

Cohort B (pembrolizumab, chemoradiation)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Overall Survival Rate

Defined as the percentage of evaluable patients who are alive at 6 months.

Secondary Outcome Measures

Incidence of Adverse Events Graded Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0

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. This data is reported in the adverse events section of this report.

Full Information

NCT ID

NCT03211117

First Posted

July 6, 2017

Last Updated

March 16, 2020

Sponsor

Mayo Clinic

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT03211117

Brief Title

Pembrolizumab, Chemotherapy, and Radiation Therapy With or Without Surgery in Treating Patients With Anaplastic Thyroid Cancer

Official Title

Phase 2 Study of Pembrolizumab Combined With Chemoradiation Therapy in Anaplastic Thyroid Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

May 2019

Overall Recruitment Status

Completed

Study Start Date

August 14, 2017 (Actual)

Primary Completion Date

February 12, 2018 (Actual)

Study Completion Date

March 28, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Mayo Clinic

Collaborators

National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Thyroid Gland Undifferentiated (Anaplastic) Carcinoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

3 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Cohort A (pembrolizumab, surgery, chemoradiation)

Arm Type

Experimental

Arm Description

Arm Title

Cohort B (pembrolizumab, chemoradiation)

Arm Type

Experimental

Arm Description

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 Type

Drug

Intervention Name(s)

Docetaxel

Other Intervention Name(s)

Docecad, RP56976, Taxotere, Taxotere Injection Concentrate

Intervention Description

Given IV

Intervention Type

Drug

Intervention Name(s)

Doxorubicin Hydrochloride

Other Intervention Name(s)

5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI), ADM, Adriacin, Adriamycin, Adriamycin Hydrochloride, Adriamycin PFS, Adriamycin RDF, ADRIAMYCIN, HYDROCHLORIDE, Adriamycine, Adriblastina, Adriblastine, Adrimedac, Chloridrato de Doxorrubicina, DOX, DOXO-CELL, Doxolem, Doxorubicin.HCl, Doxorubin, Farmiblastina, FI 106, FI-106, hydroxydaunorubicin, Rubex

Intervention Description

Given IV

Intervention Type

Radiation

Intervention Name(s)

Intensity-Modulated Radiation Therapy

Other Intervention Name(s)

IMRT, Intensity Modulated RT, Intensity-Modulated Radiotherapy

Intervention Description

Undergo IMRT

Intervention Type

Other

Intervention Name(s)

Laboratory Biomarker Analysis

Intervention Description

Correlative studies

Intervention Type

Biological

Intervention Name(s)

Pembrolizumab

Other Intervention Name(s)

Keytruda, Lambrolizumab, MK-3475, SCH 900475

Intervention Description

Given IV

Intervention Type

Procedure

Intervention Name(s)

Therapeutic Conventional Surgery

Intervention Description

Undergo surgery

Primary Outcome Measure Information:

Title

Overall Survival Rate

Description

Defined as the percentage of evaluable patients who are alive at 6 months.

Time Frame

At 6 months

Secondary Outcome Measure Information:

Title

Incidence of Adverse Events Graded Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0

Description

Time Frame

2.3 years

Other Pre-specified Outcome Measures:

Title

Number of Patients With Locoregional Recurrence and Locoregional Progression in the Thyroid Bed or Regional Lymph Nodes

Description

Will be summarized using descriptive statistics.

Time Frame

2.3 years

Title

Numbers of Patients With Distant Metastasis

Description

Will be summarized using descriptive statistics.

Time Frame

Up to 5 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ashish Chintakuntlawar

Organizational Affiliation

Mayo Clinic

Official's Role

Principal Investigator

Facility Information:

Facility Name

Mayo Clinic

City

Rochester

State/Province

Minnesota

ZIP/Postal Code

55905

Country

United States

12. IPD Sharing Statement

Learn more about this trial

Pembrolizumab, Chemotherapy, and Radiation Therapy With or Without Surgery in Treating Patients With Anaplastic Thyroid Cancer

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