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

NCT04731740 | Withdrawn Phase 2

• 1 other identifier: 73
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Metastatic Thyroid Gland Carcinoma; Poorly Differentiated Thyroid Gland Carcinoma; Thyroid Gland Anaplastic Carcinoma by AJCC V8 Stage

Outcome Measures

Primary Outcomes (2)

• Overall response rate (ORR)

  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).

  prior to study completion, average 3 years

• Overall survival at 6 months in cohort Lenvatinib+Pembrolizumab

  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.

  6 months

Secondary Outcomes (4)

• Safety Profile (Number / Severity of Serious Adverse Events, SAEs)

  SAEs will be reported in the clinical trial within 6 months of the end of the study

• Duration of Response (DoR)

  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

• Progression-Free Survival (PFS)

  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

• Overall Survival (OS)

  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 Arms (2)

Pembrolizumab + Lenvatinib

EXPERIMENTAL

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)

Drug: Lenvatinib; Biological: Pembrolizumab

Pembrolizumab + Chemotherapy

EXPERIMENTAL

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)

Biological: Pembrolizumab; Drug: Chemotherapy

Interventions

Lenvatinib DRUG

PO

Also known as: E7080, ER-203492-00

Pembrolizumab + Lenvatinib

Pembrolizumab BIOLOGICAL

IV

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

Pembrolizumab + Chemotherapy; Pembrolizumab + Lenvatinib

Chemotherapy DRUG

Investigators' choice

Pembrolizumab + Chemotherapy

Eligibility Criteria

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

You may qualify if:

• Male or female subjects ≥ 18 years of age.
• Willingness to participate in the research by signing an informed consent form approved by the research ethics committee.
• ECOG status 0 or 1 or 2.
• Measurable disease according to RECIST 1.1, as defined by the investigator.
• Patients with a histologically confirmed disease (according to the pathologist's report) that meets one of the following criteria (according to the 2010 WHO classification):
• Poorly differentiated iodine-refractory thyroid tumors in the first line or after switching to chemotherapy or investigational drugs or anaplastic thyroid cancer in the first line or after switching to chemotherapy or investigational drugs. The primary tumor may or may not be removed, but the risk of aerodigestive compression or bleeding should be excluded.
• Radioactive iodine resistant disease (RAI), which is defined by one or more of the following criteria:
• One or more measurable lesions that do not show RAI uptake.
• One or more measurable lesions progressing on RECIST 1.1 = \<14 months prior RAI therapy
• One or more measurable lesions are present after a cumulative dose of RAI\> = 600 mCi
• One or more measurable lesions that are F-18 fludeoxyglucose (FDG) -avid (\> 5 standardized absorbance value \[SUV\]) if positron emission tomography (PET) / CT is performed; these lesions can also be RAI-active
• Patients with inoperable locally advanced disease or metastases. Patients who do not want to undergo surgery or radiation are also eligible. Patients with the BRAFV600E mutation who are unable to take FDA-approved drugs, dabrafenib / trametinib, or established progression with therapy are eligible for study treatment if documented.
• Ability to collect samples, including blood and tumors, for translational studies.
• Weight over 30 kg.
• Recovery from toxicity associated with any prior treatment to grade ≤ 1, unless adverse events (AEs) are clinically significant and / or are stable with maintenance therapy.

You may not qualify if:

• The presence of a confirmed BRAF mutation.
• Concurrent participation in another clinical trial if it is not an observational (non-interventional) clinical trial or during the follow-up period of an interventional trial
• Pretreatment with any immune checkpoint inhibitor therapy (eg anti-CTLA4, -PD-1 or -PD-L1).
• Taking any type of low molecular weight kinase inhibitors (including the investigational kinase inhibitor) for 2 weeks or 5 half-lives of the agent, whichever is greater.
• Receiving any type of anti-tumor antibodies (including test antibodies) or systemic chemotherapy within 2 weeks before starting treatment.
• Current or previous use of immunosuppressants within 2 weeks prior to the first dose of study drugs, with the exception of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses that should not exceed 10 mg / day of prednisone or an equivalent corticosteroid.
• Active or previously documented autoimmune disease within the past 2 years. Note: Patients with vitiligo, Graves' disease or psoriasis who do not require systemic treatment (within the last 2 years) are not excluded.
• Active or previously documented inflammatory bowel disease (eg Crohn's disease and ulcerative colitis).
• History of allogeneic organ transplantation.
• Subjects diagnosed with immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 28 days prior to the first dose of study treatment.
• Received radiation therapy for bone metastases within 2 weeks or any other radiation therapy within 4 weeks prior to enrollment. Subjects with clinically significant ongoing complications from previous radiation therapy that have not completely resolved are not eligible for the study (eg, radiation esophagitis or other internal inflammation).
• Presence of metastases in the brain or epidural disease of the skull without adequate treatment with radiation therapy and / or surgery (including radiosurgery). Eligible patients should be neurologically asymptomatic and not receive corticosteroid medications during investigational treatment.
• Concomitant therapy with oral anticoagulants (eg warfarin, direct thrombin and factor Xa inhibitors) or platelet inhibitors (eg clopidogrel), with the exception of the following approved anticoagulants:
• Low-dose aspirin for cardioprotection (in accordance with current local guidelines) and low-dose low molecular weight heparins (LMWH).
• Anticoagulant therapy with therapeutic doses of LMWH in subjects without known brain metastases who received a dose of LMWH for at least 6 weeks prior to enrollment and who had no clinically significant hemorrhagic complications from the anticoagulation regimen or tumor.

Sponsors & Collaborators

• Saint Petersburg State University, Russia: lead

Study Sites (1)

Saint-Petersburg State University (SPSU) N.I.Pirogov Clinic of High Medical Technologies

Saint Petersburg, Russia

Location

MeSH Terms

Conditions

Thyroid Neoplasms

Interventions

lenvatinib; pembrolizumab; Drug Therapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Yuliya Mikheeva, M.D., Ph.D.

  Saint-Petersburg State University (SPSU) N.I.Pirogov Clinic of High Medical Technologies

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

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

Study Record Dates

• First Submitted: January 26, 2021
• First Posted: February 1, 2021
• Study Start: December 28, 2020
• Primary Completion: December 28, 2023
• Study Completion: December 28, 2023
• Last Updated: March 25, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

RU (1)