Neoplasms

All Conditions

Gland and Hormone Related Diseases

Rare Diseases

Carcinoma

Thyroid Neoplasms

Thyroid Diseases

Thyroid Carcinoma, Anaplastic

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Endocrine System Diseases

Endocrine Gland Neoplasms

Head and Neck Neoplasms

Anaplastic Thyroid Cancer

Antineoplastic Agents

All Drugs and Chemicals

Lenvatinib

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Experimental treatment:

Lenvatinib p.o. once a day, pembrolizumab 200 mg i.v. every 21 days started 21 days after start of Lenvatinib

Duration of treatment per patient:

until the end of month 36 after registration of the last patient or disease progression or toxicity (whichever occurs first)

Experimental treatment:

Investigators' choice of the Сhemotherapy, pembrolizumab 200 mg i.v. every 21 days started 21 days after the start of chemotherapy

Duration of treatment per patient:

until the end of month 36 after registration of the last patient or disease progression or toxicity (whichever occurs first)

Chemotherapy

Yuliya Mikheeva, M.D., Ph.D.

The aim of the study is to evaluate the efficacy of the combination of lenvatinib with pembrolizumab, and to establish a safe and effective systemic treatment regimen for patients with metastatic anaplastic thyroid cancer (ATC) / poorly differentiated thyroid cancer (PDTC).

Lenvatinib is an anti-angiogenic and antiproliferative drug used in differentiated thyroid cancer. It blocks proliferative genes such as RET and PDGFR and further inhibits major proliferation pathways such as VEGF receptor signaling and FGFR1-4.

Pembrolizumab is an immune checkpoint inhibitor that targets PD-1 located on lymphocytes. The response to pembrolizumab treatment is associated, among other things, with increased expression of PD-L1, as well as with the frequency of somatic mutations in the respective tumors. Patients with ATC / PDTC show high expression of PD-L1.

Primary endpoint

1. Objective Response Ratio (ORR) \[Time frame: prior to study completion, average 3 years\]

   * Evaluate the effectiveness of a combination of a PD-1 inhibitor (pembrolizumab) with a multikinase inhibitor (lenvatinib) using an objective response rate (ORR) in poorly differentiated or anaplastic thyroid cancer at 12 weeks and 24 weeks after starting treatment.
   * Evaluate the efficacy of the investigator's choice of chemotherapy plus PD-1 inhibitor (pembrolizumab) using an objective response rate (ORR) in poorly differentiated or anaplastic thyroid cancer at 12 weeks and 24 weeks after initiation of treatment. Includes patients with a confirmed partial (PR) and complete response (CR) as the best response according to RECIST v 1.1.
2. Overall survival at 6 months in the pembrolizumab and lenvatinib cohort \[Time frame: 6 months\]

Secondary endpoints

1. Safety Profile (Number / Severity of Serious Adverse Events, SAEs) \[Timeline: SAEs will be reported in the clinical trial within 6 months of the end of the study\]
2. Duration of Response (DoR) \[Time frame: from date of first documented clinical response (PR, CR) to date of first documented progression, date of death from any cause or patient failure, whichever comes first, is estimated to be 36 months\]
3. Progression-Free Survival (PFS) \[Time frame: from date of enrollment to date of first documented progression, date of death from any cause or patient failure, whichever is earlier, up to 36 months\]
4. Overall Survival (OS) \[Time frame: from the date of enrollment to the date of death from any cause or patient failure, whichever comes first, estimated up to 36 months\]

Study design Prospective interventional two-cohort non-comparative single-center study.

Two parallel arms based on the inclusion/exclusion criteria: Pembrolizumab+Lenvatinib or Pembrolizumab+Chemotherapy

Pembrolizumab and Lenvatinib/Chemotherapy for Poorly Differentiated/Anaplastic Thyroid Cancer

Pembrolizumab in Combination With Standard 1st Line Therapy (Lenvatinib / Chemotherapy) for Locally Advanced or Metastatic Poorly Differentiated or Anaplastic Thyroid Cancer

ORR will be calculated as the number of patients with an observed response divided by the number of patients included in the study. A two-sided confidence interval will be calculated at 80% (in accordance with the specified α) and 95% (for comparison with the literature).

Overall survival is defined as the time from the date of initiation of treatment to death from any cause that will be assessed using the Kaplan-Meier method.

Number of serious adverse events classified by severity as assessed by CTCAE v4.0

Time from the date of the first documented CR or PR to the first documented progression or death due to cancer. DoR will be determined based on tumor score (RECIST criteria version 1.1).

Median progression-free survival (mPFS) is defined as the time from the date of inclusion to the date of the first documented progression of disease or death from any cause, whichever occurs first. PFS will be determined based on the tumor score (RECIST criteria version 1.1).

Mean overall survival (mOS) is calculated as the time from the date of inclusion to the date of death for any reason.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Pembrolizumab and Lenvatinib/Chemotherapy for Poorly Differentiated/Anaplastic Thyroid Cancer	NCT04731740	Metastatic Thyr... Poorly Differen... Thyroid Gland A...	Lenvatinib Pembrolizumab Chemotherapy	18 Years -	Saint Petersburg State University, Russia
Pembrolizumab and Lenvatinib/Chemotherapy for Poorly Differentiated/Anaplastic Thyroid Cancer	NCT04731740	Metastatic Thyr... Poorly Differen... Thyroid Gland A...	Lenvatinib Pembrolizumab Chemotherapy	18 Years -	Saint Petersburg State University, Russia

Spots Global Cancer Trial Database for thyroid gland anaplastic carcinoma by ajcc v8 stage