Phase II Trial of Pembrolizumab in Metastatic or Locally Advanced Anaplastic/Undifferentiated Thyroid Cancer

NCT05119296 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: IRB-61712NCI-2022-05095
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-arm, open-label trial designed to evaluate the activity of pembrolizumab therapy in anaplastic thyroid cancer in patients with no curative alternative therapy. Pembrolizumab (Keytruda-Merck) 200 mg, given IV every 3 weeks, until evidence of progression, intolerance of treatment, withdrawal of consent or death

Conditions

Thyroid Cancer

Outcome Measures

Primary Outcomes (1)

• Overall response rate (OR)

  Overall response (OR) represents those participants that collectively achieve either complete response (CR) or partial response (PR) within 6 months, as defined below per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. * Complete Response (CR) = Disappearance of all target lesions * Partial Response (PR) = ≥ 30% decrease in the sum of the longest diameter of target lesions * Overall Response (OR) = CR + PR * Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions, and/or the appearance of one or more new lesion(s) * Stable disease (SD) = Small changes that do not meet any of the above criteria The outcome is reported as the cumulative number of participants that achieve either a CR or PR, a number without dispersion.

  5 years

Secondary Outcomes (3)

• Progression-free survival (PFS)

  2 years

• Overall survival (OS)

  2 years

• Related Adverse Events

  2 years

Study Arms (1)

Pembrolizumab 200 mg

EXPERIMENTAL

Participants will receive pembrolizumab (Keytruda) 200 mg administered by IV infusion every 3 weeks. Participants will remain on study and receive pembrolizumab for the nominal duration of treatment (35 cycles, approximately 2 years) or until there is evidence of disease progression by RECIST, unacceptable toxicity, withdrawal of consent, or discontinuation of the trial for any other reason.

Drug: Pembrolizumab (Keytruda)

Interventions

Pembrolizumab (Keytruda) DRUG

Pembrolizumab (Keytruda-Merck) 200 mg, given IV every 3 weeks, until evidence of progression, intolerance of treatment, withdrawal of consent or death

Pembrolizumab 200 mg

Eligibility Criteria

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

You may qualify if:

• Histologically- or cytologically-confirmed diagnosis of anaplastic thyroid cancer (ATC) or undifferentiated thyroid cancer (UTC). A diagnosis of possible ATC/UTC will be allowed if the clinical presentation is consistent with anaplastic or undifferentiated thyroid cancer.
• Disease characteristics one of the following:
• Unresectable ATC/UTC limited to the neck:
• Subjects must have received radiation therapy or surgery to primary tumor and have subsequent evidence of ATC/UTC.
• Metastatic ATC/UTC: either with entirely surgically-removed cancer/metastatic only disease, or with disease in the neck not requiring radiation or surgery to the neck mass
• Measurable disease per RECIST v1.1. Lesions situated in a previously-irradiated area are considered measurable if progression has been demonstrated in such lesions.
• ≥ 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 (within 7 days prior to the first dose of pembrolizumab).
• Absolute neutrophil count (ANC) ≥ 1500/µL (within 10 days prior to the first dose of pembrolizumab).
• Platelets ≥ 100 000/µL (within 10 days prior to the first dose of pembrolizumab).
• Hemoglobin ≥ 9.0 g/dL or ≥ 5.6 mmol/L (within 10 days prior to the first dose of pembrolizumab). Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks.
• Creatinine ≤ 1.5 × ULN OR Measured or calculated creatinine clearance per institutional standard ≥ 30 mL/min for subject with creatinine levels \>1.5 × institutional ULN (GFR can also be used in place of creatinine or CrCl) (test within 10 days prior to the first dose of pembrolizumab).
• Total bilirubin ≤ 1.5 × ULN OR Direct bilirubin ≤ ULN for participants with total bilirubin levels \>1.5 × ULN (test within 10 days prior to the first dose of pembrolizumab).
• AST (SGOT) and ALT (SGPT) ≤ 2.5 × ULN (≤ 5 × ULN for participants with liver metastases) (test within 10 days prior to the first dose of pembrolizumab).
• International normalized ratio (INR) ≤ 1.5 × ULN OR Prothrombin time (PT) ≤ 1.5 × ULN (Exception: subject is receiving anticoagulant therapy and PT or aPTT is within therapeutic range of intended use of anticoagulants)

You may not qualify if:

• 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).
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to study treatment start. Note: Participants must have recovered from all AEs due to previous therapies to ≤ Grade 1 or baseline. Participants with ≤ Grade 2 neuropathy may be eligible. Participants with endocrine-related AEs Grade ≤ 2 requiring treatment or hormone replacement may be eligible. Note: If the participant had major surgery, the participant must have recovered adequately from the procedure and/or any complications from the surgery prior to starting study intervention. Note: Patients who have most recently been treated with dabrafenib and/or trametinib and/or lenvatinib require a washout period of 1 week from their last dose.
• Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤ 2 weeks of radiotherapy) to non-CNS disease.
• 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.
• 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. Subject in the follow-up phase of an investigational study may participate as long as it has been ≥4 weeks after the last dose of the previous investigational agent.
• 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.
• Has a known additional malignancy that is progressing or is requiring active treatment within the past 1 year. Subjects with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
• Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, ie, without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.
• Has a history of non-infectious pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease (ILD).
• Has an active infection requiring systemic therapy.
• Has a known history of Human Immunodeficiency Virus (HIV) infection. Note: HIV testing is not required unless mandated by local health authority.
• 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 is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority
• Has active autoimmune disease that has required systemic treatment in the past 2 years (ie, 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.
• Has severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients.
• Has other co-morbid disease or intercurrent illness.

Sponsors & Collaborators

• Stanford University: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Stanford University

Palo Alto, California, 94305, United States

Location

MeSH Terms

Conditions

Thyroid Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases

Study Officials

• Saad A Khan

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 29, 2021
• First Posted: November 15, 2021
• Study Start: February 15, 2022
• Primary Completion: May 16, 2025
• Study Completion (Estimated): September 1, 2026
• Last Updated: April 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)