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

NCT03211117 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: MC1679NCI-2017-01179P30CA015083
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

Thyroid Gland Undifferentiated (Anaplastic) Carcinoma

Outcome Measures

Primary Outcomes (1)

• Overall Survival Rate

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

  At 6 months

Secondary Outcomes (1)

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

  2.3 years

Other Outcomes (2)

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

  2.3 years

• Numbers of Patients With Distant Metastasis

  Up to 5 years

Study Arms (2)

Cohort A (pembrolizumab, surgery, chemoradiation)

EXPERIMENTAL

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; Drug: Doxorubicin Hydrochloride; Radiation: Intensity-Modulated Radiation Therapy; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab; Procedure: Therapeutic Conventional Surgery

Cohort B (pembrolizumab, chemoradiation)

EXPERIMENTAL

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; Drug: Doxorubicin Hydrochloride; Radiation: Intensity-Modulated Radiation Therapy; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab

Interventions

Docetaxel DRUG

Given IV

Also known as: Docecad, RP56976, Taxotere, Taxotere Injection Concentrate

Cohort A (pembrolizumab, surgery, chemoradiation); Cohort B (pembrolizumab, chemoradiation)

Doxorubicin Hydrochloride DRUG

Given IV

Also known as: 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

Cohort A (pembrolizumab, surgery, chemoradiation); Cohort B (pembrolizumab, chemoradiation)

Intensity-Modulated Radiation Therapy RADIATION

Undergo IMRT

Also known as: IMRT, Intensity Modulated RT, Intensity-Modulated Radiotherapy

Cohort A (pembrolizumab, surgery, chemoradiation); Cohort B (pembrolizumab, chemoradiation)

Laboratory Biomarker Analysis OTHER

Correlative studies

Cohort A (pembrolizumab, surgery, chemoradiation); Cohort B (pembrolizumab, chemoradiation)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Cohort A (pembrolizumab, surgery, chemoradiation); Cohort B (pembrolizumab, chemoradiation)

Therapeutic Conventional Surgery PROCEDURE

Undergo surgery

Cohort A (pembrolizumab, surgery, chemoradiation)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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,

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Thyroid Carcinoma, Anaplastic

Interventions

Docetaxel; Doxorubicin; Radiotherapy, Intensity-Modulated; pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Results Point of Contact

• Title: Ashish V. Chintakuntlawar, MBBS, Ph.D.
• Organization: Mayo Clinic

Chintakuntlawar.Ashish@mayo.edu

(855) 776-0015

Study Officials

• Ashish Chintakuntlawar

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2017
• First Posted: July 7, 2017
• Study Start: August 14, 2017
• Primary Completion: February 12, 2018
• Study Completion: March 28, 2019
• Last Updated: March 25, 2020
• Results First Posted: August 28, 2019

Record last verified: 2019-05

Locations

US (1)