Clinical Trial: Pembrolizumab and Lenvatinib in Treating Metastatic or Recurrent Differentiated Thyroid Cancer That Cannot Be Removed by Surgery

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: Combination Targeted Therapy With Pembrolizumab and Lenvatinib in Progressive, Radioiodine-Refractory Differentiated Thyroid Cancers

Brief 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. Monoclonal antibodies, such as pembrolizumab and kinase inhibitors, such as lenvatinib, may interfere with the ability of tumor cells to grow and spread.

Detailed Summary:

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)

TERTIARY 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 P
Sponsor: Academic and Community Cancer Research United

Current Primary Outcome:

  • Confirmed response rate assessed by RECIST 1.1 (Cohort 2) [ Time Frame: Up to 3 years ]
  • CR rate assessed by RECIST 1.1 (Cohort 1) [ Time Frame: Up to 3 years ]


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Incidence of adverse events assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 [ Time Frame: Up to 3 years ]
    All patients that have initiated treatment will be considered evaluable for assessing adverse events. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine adverse event patterns. Only the grade 2+ adverse events will be assessed, regardless of relationship to the study treatment.
  • OS [ Time Frame: From registration to death due to any cause, assessed up to 3 years ]
    The distribution of survival time will be estimated using the method of Kaplan-Meier.
  • PFS [ Time Frame: From registration to the first of either death due to any cause or progression, assessed up to 3 years ]
    The distribution of PFS will be estimated using the method of Kaplan-Meier.


Original Secondary Outcome: Same as current

Information By: Academic and Community Cancer Research United

Dates:
Date Received: November 23, 2016
Date Started: April 2017
Date Completion:
Last Updated: January 24, 2017
Last Verified: November 2016