Symptoms and General Pathology

All Conditions

Neoplasms

Gland and Hormone Related Diseases

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Recurrence

Carcinoma

Thyroid Neoplasms

Thyroid Cancer, Papillary

Carcinoma, Papillary

Thyroid Diseases

Adenocarcinoma, Follicular

Leukemia-Lymphoma, Adult T-Cell

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

Endocrine System Diseases

Endocrine Gland Neoplasms

Head and Neck Neoplasms

Neoplasms, Squamous Cell

Adenocarcinoma, Papillary

Papillary Thyroid Carcinoma

Adult T-cell Leukemia/lymphoma

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Lenvatinib

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Patients receive lenvatinib PO QD on days 1-21 and pembrolizumab 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.

Laboratory Biomarker Analysis

Lenvatinib Mesylate

Bryan R Haugen

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.

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.

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

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.

Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Will use a one-stage binomial design.

Assessed by RECIST 1.1. Will use a 2-stage Simon Optimal MinMax design.

Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03. 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.

The distribution of PFS will be estimated using the method of Kaplan-Meier.

The distribution of survival at 12 months will be estimated using the method of Kaplan-Meier.

National Cancer Institute (NCI)

Academic and Community Cancer Research United

All patients that began treatment were assessed for adverse events

Cohort 1

Cohort 2

Lenvatinib-naïve patients\> Patients receive lenvatinib 20mg PO QD on days 1-21 and pembrolizumab 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.\> \> Laboratory Biomarker Analysis: Correlative studies\>

\> Lenvatinib: Given PO\>

\> Lenvatinib Mesylate: Given PO\>

\> Pembrolizumab: Given IV

Previously progressed on Lenvatinib alone\> Patients receive lenvatinib daily dose at progression QD on days 1-21 and pembrolizumab 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.\> \> Laboratory Biomarker Analysis: Correlative studies\>

\> Lenvatinib: Given PO\>

\> Lenvatinib Mesylate: Given PO\>

\> Pembrolizumab: Given IV

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Prior systemic VEGFR-active kinase inhibitor therapy

Histologic subtype of primary tumor

ECOG Performance Status

All enrolled patients were included in baseline analysis

Bryan Haugen, M.D.

All evaluable patients in cohort 1 were analyzed for this endpoint.

Complete Response Rate (Cohort 1)

All evaluable patients in cohort 2 were analyzed for this endpoint.

Confirmed Response Rate (Cohort 2)

Lenvatinib-naïve patients

\> Patients receive lenvatinib 20mg PO QD on days 1-21 and pembrolizumab 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.

\>

\> Laboratory Biomarker Analysis: Correlative studies

\>

\> Lenvatinib: Given PO

\>

\> Lenvatinib Mesylate: Given PO

\>

\> Pembrolizumab: Given IV

Previously progressed on Lenvatinib alone

\> Patients receive lenvatinib daily dose at progression QD on days 1-21 and pembrolizumab 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.

\>

\> Laboratory Biomarker Analysis: Correlative studies

\>

\> Lenvatinib: Given PO

\>

\> Lenvatinib Mesylate: Given PO

\>

\> Pembrolizumab: Given IV

All evaluable patients were analyzed for this endpoint.

Number of Patients Experiencing Grade 3+ Adverse Events

Progression Free Survival (PFS)

Overall Survival (OS)

Biomarker Levels Analysis Following Pembrolizumab and Lenvatinib Combination Therapy

Overall Study

Micronutrients

Anti-Infective Agents

Iodine

Cadexomer iodine

Anti-Infective Agents, Local

Trace Elements

Patients receive selumetinib PO BID starting on week 1, day 1 and continuing through 2 days after iodine I 131 therapy has been administered. Approximately 3 weeks after beginning treatment with selumetinib, patients receive iodine I-131 PO.

Patients receive placebo PO BID starting on week 1, day 1 and continuing through 2 days after iodine I-131 therapy has been administered. Approximately 3 weeks after beginning treatment with placebo, patients receive iodine I-131 PO.

Iodine I-131

Placebo Administration

Selumetinib

Alan L Ho

This phase II trial studies how well iodine I-131 works with or without selumetinib in treating patients with thyroid cancer that has returned (recurrent) or has spread from where it started to other places in the body (metastatic). Many thyroid cancers absorb iodine. Due to this, doctors often give radioactive iodine (iodine I-131) alone to treat thyroid cancer as part of standard practice. It is thought that the more thyroid tumors are able to absorb radioactive iodine, the more likely it is that the radioactive iodine will cause those tumors to shrink. Selumetinib may help radioactive iodine work better in patients whose tumors still absorb radioactive iodine. It is not yet known whether iodine I-131 is more effective with or without selumetinib in treating thyroid cancer.

PRIMARY OBJECTIVE:

I. To determine the response rate at 6 months following treatment with 131I (iodine I-131) in combination with placebo or selumetinib for radioactive iodine-avid (RAIA) recurrent and/or metastatic thyroid cancer.

SECONDARY OBJECTIVES:

I. To determine the best overall response following treatment with 131I in combination with placebo or selumetinib for RAIA recurrent and/or metastatic thyroid cancer.

II. To compare the progression-free survival of patients with RAIA recurrent and/or metastatic thyroid cancer treated with 131I in combination with placebo or selumetinib.

III. To compare serum thyroglobulin changes for patients with RAIA recurrent and/or metastatic thyroid cancer treated with 131I in combination with placebo or selumetinib.

IV. To evaluate the safety and tolerability of 131I in combination with placebo or selumetinib for patients with RAI-avid recurrent and/or metastatic thyroid cancer.

CORRELATIVE OBJECTIVE:

I. To explore the genomic and transcriptomic landscape of RAIA tumors for signatures that correlate to therapeutic benefit achieved with 131I in combination with placebo or selumetinib.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive selumetinib orally (PO) twice daily (BID) starting on week 1, day 1 and continuing through 2 days after iodine I-131 therapy has been administered. Approximately 3 weeks after beginning treatment with selumetinib, patients receive iodine I-131 PO.

ARM II: Patients receive placebo PO BID starting on week 1, day 1 and continuing through 2 days after iodine I-131 therapy has been administered. Approximately 3 weeks after beginning treatment with placebo, patients receive iodine I-131 PO.

After completion of study treatment, patients are followed up at 1 and 3 months, every 3 months for 12 months, and then every 6 months for 2 years.

Iodine I-131 With or Without Selumetinib in Treating Patients With Recurrent or Metastatic Thyroid Cancer

Randomized Double-Blind Phase II Study of Radioactive Iodine (RAI) in Combination With Placebo or Selumetinib for the Treatment of RAI-Avid Recurrent/Metastatic Thyroid Cancers

Will explore the genomic and transcriptomic landscape of RAIA tumors for signatures that correlate to therapeutic benefit achieved in patients with RAI-avid recurrent and/or metastatic thyroid cancer treated with 131I in combination with placebo or selumetinib. Exploratory analysis will include correlating response to tumor genotypes. Descriptive statistics and graphical techniques will be used to summarize this data by treatment arm.

A patient will be classified as a responder if they have a partial or complete response at the 6-month time point when compared to the baseline, pre-study radiologic scan(s). A Complete Response (CR) is defined as the disappearance of all target lesions and thyroglobulin measured to be less than 0.2 ng/ml. A Partial Response (PR) is defined as at least a 30% decrease in PBSD (sum of the longest diameter for all target lesions plus the sum of the long or short axis of all the target lymph nodes (depending on which axis is being used for assessments) at current evaluation) taking as reference the baseline sum of dimensions (BSD). \>

\> A patient will be classified as a responder if they have a partial or complete response at the 6-month time point. The proportion of patients with a response will be calculated and compared between the 2 Arms using a Fisher's Exact test.

The best overall response will be compared between the two arms. This comparison will be done using a chi-square test. For a patient to be classified as a response, they need a partial or complete response that is confirmed at least 4 weeks later anytime during the study.

PFS will be estimated using the Kaplan-Meier method, where the log-rank test will be used to compare the 2 treatment arms.

Changes in serum thyroglobulin levels will be compared between the 2 treatment arms using the Wilcoxon Rank-Sum test.

The maximum grade for each type of adverse event will be summarized using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The frequency and percentage of grade 3+ adverse events will be compared between the 2 treatment arms. Comparisons between arms will be made by using either the Chi-square or Fisher's Exact test.

Adverse events were collected at the end of each 28 day cycle. The max number of cycles taken was 8.

Patients receive 75 mg selumetinib PO BID starting on week 1, day 1 and continuing through 2 days after iodine I 131 therapy has been administered. Approximately 3 weeks after beginning treatment with selumetinib, patients receive iodine I-131 PO.

Arm I (Selumetinib, Iodine I-131)

Arm II (Placebo, Iodine I-131)

Ethnicity (NIH/OMB)

All patients registered to protocol treatment are included in this analysis.

Alan Ho, M.D.

All patients that began protocol treatment and were evaluable for this endpoint are included.

Response at 6 Months

Best Overall Response

Changes in Serum Thyroglobulin Levels

Incidence of Adverse Events

Genomic and Transcriptomic Landscape of Radioactive Iodine-avid (RAIA) Tumors

Carcinoma, Medullary

Carcinoma, Neuroendocrine

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Thyroid Cancer, Medullary

Neuroendocrine Tumor

Neuroepithelioma

Sunitinib

Angiogenesis Inhibitors

Growth Inhibitors

Patients receive sunitinib malate PO QD on days 1-28. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity

Pharmacogenomic Study

Sunitinib Malate

Tanguy Y Seiwert

This phase II trial studies how well sunitinib malate works in treating patients with thyroid cancer that did not respond to iodine I 131 (radioactive iodine) and cannot be removed by surgery. Sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

PRIMARY OBJECTIVES:

I. Determine the response rate of single agent sunitinib (sunitinib malate) in patients with iodine refractory, unresectable well-differentiated thyroid cancer (WDTC) who have evidence of disease progression within 6 months of study enrollment.

II. Determine the response rate of single agent sunitinib in patients with medullary thyroid cancer (MTC) who have evidence of disease progression within 6 months of study enrollment.

III. Determine the toxicity, duration of response, progression free survival, and overall survival in patients with WDTC or MTC treated with single agent sunitinib.

IV. Determine whether the presence of ret proto-oncogene (RET) gene rearrangements in patients with WDTC or RET mutations in patients with MTC predict response to sunitinib.

V. Determine whether therapy with sunitinib affects phosphorylation of downstream RET effector, mitogen-activated protein kinase 1 (ERK), in WDTC and MTC tissue.

VI. Determine whether specific germ-line polymorphisms in the RET gene are associated with favorable outcome in patients with WDTC treated with sunitinib.

OUTLINE: Patients are assigned to 1 of 2 cohorts according to type of thyroid cancer (medullary vs well-differentiated).

Patients receive sunitinib malate orally (PO) once daily (QD) on days 1-28. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically for up to 2 years.

Sunitinib Malate in Treating Patients With Thyroid Cancer That Did Not Respond to Iodine I 131 and Cannot Be Removed by Surgery

Phase II Trial of Sunitinib (SU11248) in Iodine-131 Refractory, Unresectable Differentiated Thyroid Cancers and Medullary Thyroid Cancers

Relevant laboratory correlates will be compared between responders and non-responders using the Wilcoxon rank sum test. The association between the presence or absence of RET gene rearrangements/mutations and tumor response, as well as the association between germ-line polymorphisms in the RET gene and response, will be analyzed using Fisher's exact test. The correlative and genetic data will also be entered as covariates (univariate analyses only due to the small sample size) in a Cox regression model of progression-free survival.

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR."

Any grade toxicity of any type, regardless of attribution

Kaplan-Meier curves will be generated and 95% confidence intervals will be derived for median overall survival.

Patients receive sunitinib malate PO QD on days 1-28. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity

This arm contains results for the Radioactive Iodine Refractory Thyroid Cancer Subgroup

Sunitinib Malate: Given PO

Sunitinib Malate-Radioactive Iodine Refractory Subgroup

Patients receive sunitinib malate PO QD on days 1-28. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity

This arm contains results for the Metastatic Medullary Thyroid Cancer Subgroup

Sunitinib Malate: Given PO

Sunitinib Malate-Metastatic Medullary Subgroup

Dr. Tanguy Seiwert

Note. The objective was not to compare the two arms (subgroups), but to compare each with historical data.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Lenvatinib and Pembrolizumab in Differentiated Thyroid Cancers (DTC)	NCT02973997	Columnar Cell V... Follicular Vari... Metastatic Thyr... Metastatic Thyr... Poorly Differen... Recurrent Diffe... Recurrent Thyro... Recurrent Thyro... Stage III Diffe... Stage III Thyro... Stage III Thyro... Stage IV Thyroi... Stage IV Thyroi... Stage IVA Diffe... Stage IVA Thyro... Stage IVA Thyro... Stage IVB Diffe... Stage IVB Thyro... Stage IVB Thyro... Stage IVC Diffe... Stage IVC Thyro... Stage IVC Thyro... Tall Cell Varia... Thyroid Gland H... Unresectable Di... Unresectable Th...	Laboratory Biom... Lenvatinib Lenvatinib Mesy... Pembrolizumab	18 Years -	Academic and Community Cancer Research United
Iodine I-131 With or Without Selumetinib in Treating Patients With Recurrent or Metastatic Thyroid Cancer	NCT02393690	Metastatic Thyr... Poorly Differen... Recurrent Thyro... Stage IV Thyroi... Stage IV Thyroi... Stage IVA Thyro... Stage IVA Thyro... Stage IVB Thyro... Stage IVB Thyro... Stage IVC Thyro... Stage IVC Thyro...	Iodine I-131 Placebo Adminis... Selumetinib	18 Years -	Academic and Community Cancer Research United
Sunitinib Malate in Treating Patients With Thyroid Cancer That Did Not Respond to Iodine I 131 and Cannot Be Removed by Surgery	NCT00381641	Differentiated ... Recurrent Thyro... Refractory Thyr... Stage III Thyro... Stage III Thyro... Stage IV Thyroi... Stage IV Thyroi... Stage IV Thyroi... Stage IVA Thyro... Stage IVA Thyro... Stage IVA Thyro... Stage IVB Thyro... Stage IVB Thyro... Stage IVB Thyro... Stage IVC Thyro... Stage IVC Thyro... Stage IVC Thyro... Thyroid Gland O... Unresectable Th...	Laboratory Biom... Pharmacogenomic... Sunitinib Sunitinib Malat...	18 Years -	National Cancer Institute (NCI)
Iodine I-131 With or Without Selumetinib in Treating Patients With Recurrent or Metastatic Thyroid Cancer	NCT02393690	Metastatic Thyr... Poorly Differen... Recurrent Thyro... Stage IV Thyroi... Stage IV Thyroi... Stage IVA Thyro... Stage IVA Thyro... Stage IVB Thyro... Stage IVB Thyro... Stage IVC Thyro... Stage IVC Thyro...	Iodine I-131 Placebo Adminis... Selumetinib	18 Years -	Academic and Community Cancer Research United

Spots Global Cancer Trial Database for stage ivb thyroid gland papillary carcinoma ajcc v7