Nivolumab Plus Lenvatinib Against Anaplastic Thyroid Cancer (NAVIGATION)

Study Overview
=================
Brief Summary
-----------------
This study is an open-label phase 2 study to evaluate the safety and efficacy of Nivolumab plus Lenvatinib in patients with unresectable anaplastic thyroid cancer.

Detailed Description
-----------------
This study is an open-label phase 2 study to evaluate the safety and efficacy of Nivolumab plus Lenvatinib in patients with unresectable anaplastic thyroid cancer according to the following steps. Step 1 will evaluate the dose-limiting toxicities (DLT) of Nivolumab plus Lenvatinib in patients with unresectable anaplastic thyroid cancer. Step 2 will evaluate the safety and efficacy of Nivolumab plus Lenvatinib in patients with unresectable anaplastic thyroid cancer.

Official Title
-----------------
Phase 2 Study of Nivolumab Plus Lenvatinib for Patients With Unresectable Anaplastic Thyroid Cancer (NAVIGATION Study)

Conditions
-----------------
Anaplastic Thyroid Cancer

Intervention / Treatment
-----------------
* Drug: Lenvatinib
* Drug: Nivolumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically confirmed as anaplastic thyroid cancer Unresectable anaplastic thyroid cancer Have measurable lesions defined by the RECIST version 1.1 Have adequate organ function Cardiac function test within 28 days before enrollment 12-lead electrocardiogram no clinically significant abnormality as shown below: heart disease, severe arrhythmia, etc. Patients who are 20 years or older Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Ability to swallow oral medications Women of childbearing potential Life expectancy of more than 90 days Have signed written informed consent to participate in this study Exclusion Criteria: Active brain metastases or leptomeningeal metastases Diverticulitis or Symptomatic ulcerative disease Treatment required complication of systemic infectious disease Medical history of active, known, or suspected autoimmune disease Complication of pulmonary fibrosis or interstitial pneumonitis Medical history of clinically significant cardiovascular disease within 180 days of initial dose as New York Heart Association (NYHA) class above 2 leveled congestive heart failure, unstable angina, cardiac infarction or cardiac arrhythmia with paroxysmal or required treatment Regardless of usage of antihypertensive drug, systolic blood pressure <=140 mm Hg and diastolic blood pressure <=90 mm Hg Have active double cancer Currently receiving other interventional clinical study treatment

Ages Eligible for Study
-----------------
Minimum Age: 20 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lenvatinib plus Nivolumab<br>Step 1: 3 patients, Step 2: 48 patients | Drug: Lenvatinib<br>* Lenvatinib will be administered at a dose of 24mg as oral dose, one a day<br>Drug: Nivolumab<br>* Nivolumab will be administered at a dose of 240mg as a 30-minutes IV infusion, every 2 weeks<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Step 1: Proportion of subjects with Dose-Limiting Toxicities (DLT) | Proportion of subjects with DLT will be defined as the proportion of patients who developed DLT | up to 28 days | 
| Step 2: Objective Response Rate (ORR) | ORR will be defined as the proportion of patients achieving complete response (CR) and partial response (PR) as determined according to RECIST ver1.1 by a central review | Up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of adverse events | For adverse events due to protocol treatment, determine the frequency of worst grades in all courses according to CTCAE v5.0 | Up to 12 months | 
| Overall Survival (OS) | The period will be from the day of enrollment, as the starting date of the computation, to the day of death of any cause. | Up to 12 months | 
| Progression-Free Survival (PFS) | The registration date is the starting date, and is defined as the period until the progressive disease (PD) or death of any cause occurs. | Up to 12 months | 
| Best Overall Response (BOR) | BOR is the best response recorded from the start of the study treatment until the end of treatment | Up to 12 months | 
| Disease Control Rate (DCR) | DCR will be defined as the proportion of patients achieving CR, PR or stable disease (SD). | Up to 12 months | 
| Clinical Benefit Rate (CBR) | DCR will be defined as the proportion of patients achieving CR, PR or SD lasting at least 11 months. | Up to 12 months | 
| Quality of life by EuroQol 5 dimensions 5-level (EQ-5D-5L) | Quality of life will be evaluated by EQ-5D-5L | Up to 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Nivolumab, Lenvatinib, Anaplastic Thyroid Cancer