Clinical Trials Directory

Trials / Completed

CompletedNCT02973997

Lenvatinib and Pembrolizumab in Differentiated Thyroid Cancers (DTC)

Combination Targeted Therapy With Pembrolizumab and Lenvatinib in Progressive, Radioiodine-Refractory Differentiated Thyroid Cancers: A Phase II Study

Status
Completed
Phase
Phase 2
Study type
Interventional
Enrollment
57 (actual)
Sponsor
Academic and Community Cancer Research United · Academic / Other
Sex
All
Age
18 Years
Healthy volunteers
Not accepted

Summary

This phase II trial studies how well pembrolizumab and lenvatinib work in treating patients with differentiated thyroid cancer that has spread to other places in the body or has come back and cannot be removed by surgery. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Detailed description

PRIMARY OBJECTIVES: I. To investigate the clinical efficacy, as indicated by the rate of complete response (CR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, of combination therapy with pembrolizumab and lenvatinib in lenvatinib-naive patients with progressive radioiodine-refractory differentiated thyroid cancers (DTC). (Cohort 1) II. To determine the overall response rate (ORR) by the addition of pembrolizumab to patients with radioiodine-refractory DTC who have progressive disease on lenvatinib alone. (Cohort 2) SECONDARY OBJECTIVES: I. To determine the safety profile and toxicity of combination therapy with pembrolizumab and lenvatinib in patients with progressive DTC. (Cohort 1 and cohort 2) II. To determine progression-free survival (PFS) and overall survival (OS). (Cohort 1 and cohort 2) CORRELATIVE RESEARCH OBJECTIVES: I. To correlate tumor response (RECIST 1.1) with pretreatment frequency of CD8+ T cells in the primary and/or metastatic tumor. (Cohort 1 and cohort 2) II. To correlate tumor response (RECIST 1.1) with pretreatment PD-L1 and PD-L2 levels in the primary and/or metastatic tumor. (Cohort 1 and cohort 2) III. To correlate tumor response (RECIST 1.1) with pretreatment frequency of lymphocytes expressing CD3, CD4, PD-1, FoxP3, or CD20, and of CD163+ macrophages. (Cohort 1 and cohort 2) IV. To correlate tumor response (RECIST 1.1) with the phenotype and frequency of key leukocyte subsets (i.e., PD-1+ T cells, regulatory T cells \[Tregs\], myeloid subsets) in the peripheral blood before, at 6 and 18 weeks on therapy, and at 54 weeks (study completion), progressive disease (PD), or study withdrawal. (Cohort 1) V. To correlate tumor response (RECIST 1.1) with PD-1+ T cell functional capacity. (Cohort 1) VI. To correlate tumor response (RECIST 1.1) with serum anti-thyroglobulin antibody levels assessed before, and at 18 weeks on therapy. (Cohort 1 and 2) VII. To correlate tumor response (RECIST 1.1) with tumor mutation status. (Cohort 1) VIII. To broadly investigate mechanisms of response and resistance to combination therapy, gene expression profiles will be generated from frozen biopsies for analysis by ribonucleic acid-sequencing (RNA-Seq). (Cohort 1) OUTLINE: Patients receive lenvatinib orally (PO) once daily (QD) on days 1-21 and pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for up to 19 cycles in the absence of disease progression or unacceptable toxicity. Patients may continue treatment for up to 35 cycles. After completion of study treatment, patients are followed up every 3 months for up to 3 years.

Conditions

Interventions

TypeNameDescription
OTHERLaboratory Biomarker AnalysisCorrelative studies
DRUGLenvatinibGiven PO
DRUGLenvatinib MesylateGiven PO
BIOLOGICALPembrolizumabGiven IV

Timeline

Start date
2018-02-07
Primary completion
2022-08-15
Completion
2023-10-08
First posted
2016-11-28
Last updated
2025-08-29
Results posted
2023-10-24

Locations

7 sites across 1 country: United States

Regulatory

Source: ClinicalTrials.gov record NCT02973997. Inclusion in this directory is not an endorsement.