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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03211117
Recruitment Status : Completed
First Posted : July 7, 2017
Results First Posted : August 28, 2019
Last Update Posted : March 25, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic

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.

Condition or disease Intervention/treatment 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

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 2 Study of Pembrolizumab Combined With Chemoradiation Therapy in Anaplastic Thyroid Cancer
Actual Study Start Date : August 14, 2017
Actual Primary Completion Date : February 12, 2018
Actual Study Completion Date : March 28, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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:
  • Docecad
  • RP56976
  • Taxotere
  • Taxotere Injection Concentrate

Drug: Doxorubicin Hydrochloride
Given IV
Other Names:
  • 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

Radiation: Intensity-Modulated Radiation Therapy
Undergo IMRT
Other Names:
  • IMRT
  • Intensity Modulated RT
  • Intensity-Modulated Radiotherapy

Other: Laboratory Biomarker Analysis
Correlative studies

Biological: Pembrolizumab
Given IV
Other Names:
  • Keytruda
  • Lambrolizumab
  • MK-3475
  • SCH 900475

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:
  • Docecad
  • RP56976
  • Taxotere
  • Taxotere Injection Concentrate

Drug: Doxorubicin Hydrochloride
Given IV
Other Names:
  • 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

Radiation: Intensity-Modulated Radiation Therapy
Undergo IMRT
Other Names:
  • IMRT
  • Intensity Modulated RT
  • Intensity-Modulated Radiotherapy

Other: Laboratory Biomarker Analysis
Correlative studies

Biological: Pembrolizumab
Given IV
Other Names:
  • Keytruda
  • Lambrolizumab
  • MK-3475
  • SCH 900475




Primary Outcome Measures :
  1. Overall Survival Rate [ Time Frame: At 6 months ]
    Defined as the percentage of evaluable patients who are alive at 6 months.


Secondary Outcome Measures :
  1. Incidence of Adverse Events Graded Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 [ Time Frame: 2.3 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. This data is reported in the adverse events section of this report.


Other Outcome Measures:
  1. Number of Patients With Locoregional Recurrence and Locoregional Progression in the Thyroid Bed or Regional Lymph Nodes [ Time Frame: 2.3 years ]
    Will be summarized using descriptive statistics.

  2. Numbers of Patients With Distant Metastasis [ Time Frame: Up to 5 years ]
    Will be summarized using descriptive statistics.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03211117


Locations
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United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Ashish Chintakuntlawar Mayo Clinic
  Study Documents (Full-Text)

Documents provided by Mayo Clinic:
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Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT03211117    
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 )
First Posted: July 7, 2017    Key Record Dates
Results First Posted: August 28, 2019
Last Update Posted: March 25, 2020
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Thyroid Neoplasms
Thyroid Carcinoma, Anaplastic
Thyroid Diseases
Endocrine System Diseases
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Docetaxel
Doxorubicin
Liposomal doxorubicin
Pembrolizumab
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Antineoplastic Agents, Immunological