Nivolumab Plus Lenvatinib Against Anaplastic Thyroid Cancer (NAVIGATION)

Phase 2

Active, not recruiting

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Lenvatinib plus Nivolumab	Nivolumab	Step 1: 3 patients, Step 2: 48 patients
Lenvatinib plus Nivolumab	Lenvatinib	Step 1: 3 patients, Step 2: 48 patients

Primary Outcome Measures

Name	Time	Method
Step 2: Objective Response Rate (ORR)	Up to 12 months	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
Step 1: Proportion of subjects with Dose-Limiting Toxicities (DLT)	up to 28 days	Proportion of subjects with DLT will be defined as the proportion of patients who developed DLT

Secondary Outcome Measures

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

Locations (10): Nippon Medical School Hospital
🇯🇵
Tokyo, Japan
Osaka Metropolitan University Hospital
🇯🇵
Osaka, Japan
Aichi Cancer Center
🇯🇵
Nagoya, Aichi, Japan
Kobe University Hospital
🇯🇵
Kobe, Hyogo, Japan
Hyogo Cancer Center
🇯🇵
Akashi, Hyogo, Japan
National Cancer Center Hospital
🇯🇵
Tokyo, Japan
Yokohama City University Hospital
🇯🇵
Yokohama, Kanagawa, Japan
Tohoku University Hospital
🇯🇵
Sendai, Miyagi, Japan
Hokkaido University Hospital
🇯🇵
Hokkaido, Japan
National Cancer Center Hospital East
🇯🇵
Kashiwa, Chiba, Japan