IMRT Followed by Pembrolizumab in the Adjuvant Setting in Anaplastic Cancer of the Thyroid (IMPAACT): Phase II Trial Adjuvant Pembrolizumab After IMRT in ATC

This is an open label, single center, phase 2 trial of adjuvant pembrolizumab after external beam radiation to the primary tumor in patients with stage IVB (disease localized to the neck) ATC. This drug trial will estimate the median progression-free survival (PFS) (from the start of adjuvant pembrolizumab until locoregional progression, development of distant metastatic disease, or death) in stage IVB ATC patients with gross disease, treated with external beam radiation (+/- concomitant chemotherapy) followed by adjuvant pembrolizumab. Patients will be patients enrolled from cohort 1 and 2 (cohort 1: ≥51 Gy; cohort 2: ≤50 Gy).

Study Overview

• Status: Terminated
• Conditions: Thyroid
• Intervention / Treatment: Drug: Pembrolizumab

Detailed Description

Primary Objective:

-To estimate the median progression-free survival (PFS) (from the start of adjuvant pembrolizumab until locoregional progression, development of distant metastatic disease, or death) in stage IVB ATC patients with gross disease, treated with external beam radiation (+/- concomitant chemotherapy) followed by adjuvant pembrolizumab. Patients will be patients enrolled from cohort 1 and 2 (cohort 1: ≥51 Gy; cohort 2: ≤50 Gy).

Secondary Objective:

-To estimate median overall survival in stage IVB ATC patients treated with external beam radiation (+/- concurrent chemotherapy) followed by adjuvant pembrolizumab. Patients will be stratified by dose of external beam radiation.

Exploratory Objective:

-To estimate the median disease-free survival (DFS) in patients with stage IVB ATC treated with surgery/external beam radiation/concomitant chemotherapy followed by adjuvant pembrolizumab (cohort 3).

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male/female participants who are at least 18 years of age on the day of signing informed consent with Pathologic findings supporting the clinical impression of anaplastic thyroid carcinoma will be enrolled in this study. Diagnosis may include consistent with or suggestive of terminology associated with: anaplastic thyroid carcinoma, undifferentiated carcinoma, squamous carcinoma; carcinoma with spindled, giant cell, or epithelial features; poorly differentiated carcinoma with pleomorphism, extensive necrosis with tumor cells present.
2. Stage IVB disease (no convincing evidence of metastatic disease outside of the neck) who have unresectable disease are eligible in groups 1 or 2. Previous excisional biopsy is permitted.
3. Stage IVB disease (no convincing evidence of metastatic disease outside of the neck) who have undergone complete resection of tumor (no convincing evidence of metastatic disease in the neck) are eligible in group 3
4. Patient must have completed external beam radiation with or without concomitant cytotoxic chemotherapy to participate in groups 1 and 2. Those who have completed these treatment after surgical resection of primary tumor may participate in group 3.
5. Patients may enroll only after completing radiation. Study drug may start from 2-6 weeks (+2 weeks) after radiation is completed and can only be started once radiation and chemotherapy-related toxicities are grade 2 or less (with the exception of alopecia). If a subject is consented but AEs are not grade 2 or less by 8 weeks after RT is completed, that subject is not eligible and should not start pembrolizumab.

6. A female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies:

   1. Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR
   2. A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 120 days after the last dose of study treatment.
7. A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 32 weeks (5 terminal half-lives for pembrolizumab plus an additional 90 days) from the last dose of study treatment and refrain from donating sperm during this period.
8. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
9. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention.
10. Adequate organ function as defined in the following table (Table 1). Specimens must be collected within 10 days prior to the start of study intervention.

Exclusion Criteria:

1. A WOCBP who has a positive urine pregnancy test within 72 hours prior to first dose of pembrolizumab (see Appendix 3). A serum pregnancy test will be required.
2. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
3. Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
4. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
5. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
6. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
7. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
8. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease, not related to radiation.
9. Has an active infection requiring systemic therapy.
10. Has a known history of Human Immunodeficiency Virus (HIV) infection.
11. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA qualitative is detected) infection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pembrolizumab; The infusions are given every 6 weeks	Drug: Pembrolizumab; Given by IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Progression-free Survival (PFS) in Stage IVB ATC Patients With Gross Disease Treated With External Beam Radiation Followed by Adjuvant Pembrolizumab	To estimate the median progression-free survival (PFS) (from the start of adjuvant pembrolizumab until locoregional progression, development of distant metastatic disease, or death) in stage IVB ATC patients with gross disease, treated with external beam radiation (+/- concomitant chemotherapy) followed by adjuvant pembrolizumab. Patients will be patients enrolled from cohort 1 and 2 cohort 1: >51 Gy; cohort 2: <50 Gy).	From the start of adjuvant pembrolizumab until disease progression or death
Median Overall Survival (OS) in Stage IVB ATC Patients Treated With External Beam Radiation Followed by Adjuvant Pembrolizumab	To estimate median overall survival in stage IVB ATC patients treated with external beam radiation (+/- concurrent chemotherapy) followed by adjuvant pembrolizumab. Patients will be stratified by dose of external beam radiation.	From the start of adjuvant pembrolizumab until disease progression or death

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Disease-free Survival (DFS) in Patients With Stage IVB ATC Treated With Surgery/External Beam Radiation/Concomitant Chemotherapy Followed by Adjuvant Pembrolizumab	To estimate the median disease-free survival (DFS) in patients with stage IVB ATC treated with surgery/external beam radiation/concomitant chemotherapy followed by adjuvant pembrolizumab (cohort 3).	From the start of adjuvant pembrolizumab until disease progression or death

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Investigators: Principal Investigator: Maria Cabanillas, MD, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• M D Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): February 11, 2022
• Primary Completion (Actual): July 1, 2025
• Study Completion (Actual): July 1, 2025

Study Registration Dates

• First Submitted: September 15, 2021
• First Submitted That Met QC Criteria: September 17, 2021
• First Posted (Actual): September 28, 2021

Study Record Updates

• Last Update Posted (Actual): March 23, 2026
• Last Update Submitted That Met QC Criteria: March 2, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Thyroid Diseases; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; pembrolizumab
• Other Study ID Numbers: 2021-0704; NCI-2021-10669 (Other Identifier: NCI-CTRP Clinical Trials Reporting Registry)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No