Nivolumab Plus Lenvatinib Against Anaplastic Thyroid Cancer (NAVIGATION)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Anaplastic Thyroid Cancer
• Intervention / Treatment: Drug: Lenvatinib; Drug: Nivolumab

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.

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 464-8681
      • Aichi Cancer Center
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East
  • Hokkaido
    • Hokkaido, Hokkaido, Japan, 060-8648
      • Hokkaido University Hospital
  • Hyōgo
    • Akashi, Hyōgo, Japan, 673-8558
      • Hyogo Cancer Center
    • Kobe, Hyōgo, Japan, 650-0017
      • Kobe University Hospital
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 236-0004
      • Yokohama City University Hospital
  • Miyagi
    • Sendai, Miyagi, Japan, 980-8574
      • Tohoku University Hospital
  • Osaka
    • Osaka, Osaka, Japan, 545-8586
      • Osaka Metropolitan University Hospital
  • Tokyo
    • Tokyo, Tokyo, Japan, 113-8603
      • Nippon Medical School Hospital
    • Tokyo, Tokyo, Japan, 104-0045
      • National Cancer Center Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically confirmed as anaplastic thyroid cancer
2. Unresectable anaplastic thyroid cancer
3. Have measurable lesions defined by the RECIST version 1.1
4. Have adequate organ function
5. Cardiac function test within 28 days before enrollment 12-lead electrocardiogram no clinically significant abnormality as shown below: heart disease, severe arrhythmia, etc.
6. Patients who are 20 years or older
7. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
8. Ability to swallow oral medications
9. Women of childbearing potential
10. Life expectancy of more than 90 days
11. Have signed written informed consent to participate in this study

Exclusion Criteria:

1. Active brain metastases or leptomeningeal metastases
2. Diverticulitis or Symptomatic ulcerative disease
3. Treatment required complication of systemic infectious disease
4. Medical history of active, known, or suspected autoimmune disease
5. Complication of pulmonary fibrosis or interstitial pneumonitis
6. 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
7. Regardless of usage of antihypertensive drug, systolic blood pressure <=140 mm Hg and diastolic blood pressure <=90 mm Hg
8. Have active double cancer
9. Currently receiving other interventional clinical study treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

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

Collaborators and Investigators

• Sponsor: National Cancer Center Hospital East
• Collaborators: Ono Pharmaceutical Co. Ltd
• Investigators: Study Director: Makoto Tahara, MD, PhD, National Cancer Center Hospital East; Study Chair: Naomi Kiyota, MD, PhD, Kobe University Hospital; Study Chair: Iwao Sugitani, MD, PhD, Nippon Medical School Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 2, 2019
• Primary Completion (Actual): September 10, 2025
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: January 13, 2023
• First Submitted That Met QC Criteria: January 13, 2023
• First Posted (Actual): January 25, 2023

Study Record Updates

• Last Update Posted (Actual): April 9, 2026
• Last Update Submitted That Met QC Criteria: April 6, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Nivolumab; Lenvatinib; Anaplastic Thyroid Cancer
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Thyroid Carcinoma, Anaplastic; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Nivolumab; lenvatinib
• Other Study ID Numbers: YCU18001; JapicCTI-194835 (Registry Identifier: JAPIC Clinical Trials Information)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No