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

Thyroid Carcinoma, Anaplastic

Carcinoma, Medullary

Carcinoma, Neuroendocrine

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Anaplastic Thyroid Cancer

Thyroid Cancer, Medullary

Neuroendocrine Tumor

Neuroepithelioma

Antibodies

Immunoglobulins

Patients with differentiated thyroid cancer (DTC) receive 800 mg pazopanib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients with medullary thyroid cancer (MTC) receive 800 mg pazopanib hydrochloride PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients with anaplastic thyroid cancer (ATC) receive 800 mg pazopanib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients with confirmed, differentiated thyroid cancer (DTC) who are thyroglobulin antibody negative receive 800 mg pazopanib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Pazopanib Hydrochloride

Keith C Bible

This phase II trial studies the side effects and how well pazopanib hydrochloride works in treating patients with advanced thyroid cancer. Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by stopping blood flow to the tumor.

PRIMARY OBJECTIVE:

I. To establish the safety and efficacy of GW786034 (pazopanib hydrochloride) as a therapeutic in patients afflicted with differentiated, medullary and anaplastic thyroid cancers.

CORRELATIVE OBJECTIVES:

I. Assessment of the impact of therapy with GW786034 on serum/plasma vascular endothelial growth factor (VEGF) levels.

II. To explore the potential relationship between changes in thyroglobulin levels and tumor response in patients with advanced differentiated thyroid cancer known to be thyroglobulin antibody negative.

OUTLINE:

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

After completion of study treatment, patients are followed up every 6 months for up to 3 years after registration.

Pazopanib Hydrochloride in Treating Patients With Advanced Thyroid Cancer

A Phase II Study of GW 786034 (Pazopanib) in Advanced Thyroid Cancer

Blood markers for angiogenesis including levels of free VEGF, free GW786034, and GW786034/VEGF complexes will be evaluated before and during therapy. Changes in these levels will largely be explored in a graphical manner as well as exploring any potential relationships between these levels and clinical outcome such as response or progression-free rate and toxicity incidence.

The proportion of patients who have not failed treatment due to disease progression, adverse reactions, refusal for further participation, or who went on to alternate therapy at 6 months (3 months for anaplastic thyroid cancer patients) will be calculated and summarized independently within each of the patient groups. Assuming that the incidence of response is binomially distributed, 90% binomial confidence intervals will also be calculated.

Overall survival time is defined as the time from registration to death due to any cause. The median is estimated using the Kaplan-Meier estimator.\> Estimated using the method of Kaplan-Meier.

Estimated using the method of Kaplan-Meier.

Duration of response is defined for all evaluable patients who have achieved a confirmed response as the date at which the patient's objective status is first noted to be a CR or PR to the earliest date progression (PD) is documented. The distribution of duration of response will be estimated using the method of Kaplan-Meier. (CR: Disappearance of all evidence of disease, PR: Regression of measurable disease and no new sites, PD: Any new lesion or increase by \>= 50% of previously involved sites from nadir). Duration of response will be assessed.

The tumor response rate is defined as the percentage of eligible patients who fulfill RECIST 1.0 for a complete or partial response at two consecutive assessments at least 8 weeks apart for patients in Cohorts 1-3. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by 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.

The confirmed tumor response rate is defined as the percentage of eligible patients who fulfill RECIST 1.0 for a complete or partial response at two consecutive assessments at least 8 weeks apart for patients with differentiated thyroid cancer who are thyroglobulin antibody negative. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by 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.

Toxicity (defined as grade 3+ adverse events deemed possibly, probably, or definitely related to treatment) will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. The percentage of patients with grade 3+ adverse events deemed possibly, probably, or definitely related to treatment are reported for patients in Cohorts 1-3.

Progression free survival at 6 months (PFS6) is defined as the proportion of patients alive and without progression at 6 months. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0.

Progression free survival at 3 months (PFS6) is defined as the proportion of patients alive and without progression at 3 months. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0.

Adverse events were collected at the end of every 28 day cycle, up to 84 cycles.

Cohort 1 (DTC)

Cohort 2 (MTC)

Cohort 3 (ATC)

Expansion Cohort (DTC)

Ethnicity (NIH/OMB)

Singapore

China

Taiwan

Australia

All patients that registered and evaluable for any of the endpoints were included in this summary.

Keith C. Bible, M.D., Ph.D.

Patients with differentiated thyroid cancer (DTC) receive 800 mg pazopanib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.\> \> Laboratory Biomarker Analysis: Correlative studies\>

\> Pazopanib Hydrochloride: Given PO

Patients with medullary thyroid cancer (MTC) receive 800 mg pazopanib hydrochloride PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.\>

\> Pazopanib Hydrochloride: Given PO

Patients with anaplastic thyroid cancer (ATC) receive 800 mg pazopanib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.\>

\> Laboratory Biomarker Analysis: Correlative studies

Patients with confirmed, differentiated thyroid cancer (DTC) who are thyroglobulin antibody negative receive 800 mg pazopanib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.\> \> Laboratory Biomarker Analysis: Correlative studies\>

\> Pazopanib Hydrochloride: Given PO

All patients in Cohort 1, Cohort 2, and Cohort 3 that received treatment and were eligible for response assessment were included in this analysis.

Overall Response Rate (in Cohorts 1-3)

All patients that registered to the Differential Thyroid Expansion cohort and were evaluable for response assessment were included in this analysis.

Confirmed Tumor Response (in the Differentiated Thyroid Cancer Expansion Cohort)

All patients that received protocol treatment and were assessed for adverse events are included in this analysis.

Toxicity as Measured by the Percentage of Patients Reporting a Grade 3+ Adverse Event Deemed Possibly, Probably, or Definitely Related to Treatment

All patients in Cohort 1 and Cohort 2 that received treatment and were eligible for response assessment were included in this analysis.

Progression-Free Survival at 6 Months (Cohorts 1 and 2 Only)

All patients from Cohort 3 that were treated and evaluable for response were included in this analysis.

Progression-Free Survival at 3 Months (Cohort 3 Only)

Change in Blood Markers for Angiogenesis

Proportion of Patients With Differentiated Thyroid Cancer and Medullary Thyroid Cancer Who Have Not Failed Treatment at 6 Months (3 Months for Anaplastic Thyroid Cancer)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
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
Pazopanib Hydrochloride in Treating Patients With Advanced Thyroid Cancer	NCT00625846	Recurrent Thyro... Stage III Diffe... Stage III Thyro... 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... Thyroid Gland A...	Laboratory Biom... Pazopanib Hydro...	19 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for stage iii differentiated thyroid gland carcinoma ajcc v7