Lenvatinib and Pembrolizumab in DTC
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02973997|
Recruitment Status : Recruiting
First Posted : November 28, 2016
Last Update Posted : June 11, 2019
|Condition or disease||Intervention/treatment||Phase|
|Columnar Cell Variant Thyroid Gland Papillary Carcinoma Follicular Variant Thyroid Gland Papillary Carcinoma Poorly Differentiated Thyroid Gland Carcinoma Recurrent Thyroid Gland Carcinoma Stage III Differentiated Thyroid Gland Carcinoma AJCC v7 Stage III Thyroid Gland Follicular Carcinoma AJCC v7 Stage III Thyroid Gland Papillary Carcinoma AJCC v7 Stage IV Thyroid Gland Follicular Carcinoma AJCC v7 Stage IV Thyroid Gland Papillary Carcinoma AJCC v7 Stage IVA Differentiated Thyroid Gland Carcinoma AJCC v7 Stage IVA Thyroid Gland Follicular Carcinoma AJCC v7 Stage IVA Thyroid Gland Papillary Carcinoma AJCC v7 Stage IVB Differentiated Thyroid Gland Carcinoma AJCC v7 Stage IVB Thyroid Gland Follicular Carcinoma AJCC v7 Stage IVB Thyroid Gland Papillary Carcinoma AJCC v7 Stage IVC Differentiated Thyroid Gland Carcinoma AJCC v7 Stage IVC Thyroid Gland Follicular Carcinoma AJCC v7 Stage IVC Thyroid Gland Papillary Carcinoma AJCC v7 Tall Cell Variant Thyroid Gland Papillary Carcinoma Thyroid Gland Hurthle Cell Carcinoma||Other: Laboratory Biomarker Analysis Drug: Lenvatinib Biological: Pembrolizumab||Phase 2|
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)
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)
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 courses in the absence of disease progression or unacceptable toxicity. Patients may continue treatment for up to 35 courses.
After completion of study treatment, patients are followed up every 3 months for up to 3 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Combination Targeted Therapy With Pembrolizumab and Lenvatinib in Progressive, Radioiodine-Refractory Differentiated Thyroid Cancers: A Phase II Study|
|Actual Study Start Date :||February 7, 2018|
|Estimated Primary Completion Date :||October 8, 2021|
|Estimated Study Completion Date :||September 30, 2022|
Experimental: Treatment (lenvatinib, pembrolizumab)
Patients receive lenvatinib mesylate PO QD on days 1-21 and pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 19 courses in the absence of disease progression or unacceptable toxicity. Patients may continue treatment for up to 35 courses.
Other: Laboratory Biomarker Analysis
- Complete response (CR) rate assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (Cohort 1) [ Time Frame: Up to 3 years ]Will use a one-stage binomial design.
- Confirmed response rate assessed by RECIST 1.1 (Cohort 2) [ Time Frame: Up to 3 years ]Will use a 2-stage Simon Optimal MinMax design.
- 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.
- Progression free survival (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.
- Overall survival (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.
- Biomarker levels analysis following pembrolizumab and lenvatinib combination therapy [ Time Frame: Up to 3 years ]All analyses with respect to the translational component of this study are intended to be hypothesis-generating and descriptive in manner. Clinical data (i.e. CR rates confirmed response rates, PFS, OS, etc.) will be correlated with tumor marker data of interest (CD8+, PD-L1, PD-L2, T cell functional capacity markers, anti-thyroglobulin antibody levels, tumor mutation status, and other markers). The Chi-Square (or Fisher?s Exact test) will be used to assess the association of categorical clinical data with categorical biomarker data. Time-to-event clinical data (PFS, OS) will be correlated with biomarker data using Kaplan-Meier methodology and Cox regression models. Logistic regression models will also be used to predict binary clinical data with baseline biomarker data. Finally, graphical methods and descriptive statistics will be used to summarize the data as well. Two-sided p-values < 0.05 will be considered statistically significant.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02973997
|United States, California|
|Stanford Cancer Institute Palo Alto||Withdrawn|
|Palo Alto, California, United States, 94304|
|Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center||Recruiting|
|Torrance, California, United States, 90502|
|Contact: Emily Ong 310-222-8172 email@example.com|
|Principal Investigator: Andrew G. Gianoukakis|
|United States, Colorado|
|University of Colorado Hospital||Recruiting|
|Aurora, Colorado, United States, 80045|
|Contact: Paula Fisk 720-848-0676 firstname.lastname@example.org|
|Principal Investigator: Daniel W. Bowles|
|United States, Massachusetts|
|Massachusetts General Hospital Cancer Center||Recruiting|
|Boston, Massachusetts, United States, 02114|
|Contact: Lori J. Wirth 617-724-6000 email@example.com|
|Principal Investigator: Lori J. Wirth|
|United States, Michigan|
|University of Michigan Comprehensive Cancer Center||Recruiting|
|Ann Arbor, Michigan, United States, 48109|
|Contact: Gregory W. Campbell 734-647-9075 firstname.lastname@example.org|
|Principal Investigator: Francis P. Worden|
|United States, New York|
|Memorial Sloan Kettering Cancer Center||Recruiting|
|New York, New York, United States, 10065|
|Contact: Hisham Elsayed 646-888-5334 email@example.com|
|Principal Investigator: Eric J. Sherman|
|United States, Ohio|
|Ohio State University Comprehensive Cancer Center||Recruiting|
|Columbus, Ohio, United States, 43210|
|Contact: James Line 614-293-5066 James.Line@osumc.edu|
|Principal Investigator: Bhavana Konda|
|United States, Tennessee|
|Vanderbilt University/Ingram Cancer Center||Withdrawn|
|Nashville, Tennessee, United States, 37232|
|United States, Texas|
|M D Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Danielle Litofsky 713-794-1472 Dgutterm@mdanderson.org|
|Principal Investigator: Ramona Dadu|
|Principal Investigator:||Bryan R Haugen||Academic and Community Cancer Research United|