Study of the Safety and Activity of Lenvatinib (E7080) in Subjects With KIF5B-RET-Positive Adenocarcinoma of the Lung

NCT01877083 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: E7080-G000-209
• Study Type: interventional
• Target: 25
• Locations: 5 countries
• Sites: 23

Brief Summary

This is a Phase 2, open-label, safety and activity study of lenvatinib in subjects with KIF5B-RET-positive adenocarcinoma of the lung and other confirmed RET translocations. At least 20 subjects with KIF5B-RET and other RET translocations will be treated and will receive lenvatinib at a starting dose of 24 mg orally, once per day. The study will consist of 3 phases: The Pretreatment Phase, The Treatment Phase and the Extension Phase. The Pretreatment Phase will include screening procedures and eligibility assessments. The Pretreatment Phase consists of a Screen 1, Screen 2 and Baseline Period. The Treatment Phase will begin when the subject has met all eligibility criteria on Day 1 of the first Treatment Cycle. The Treatment Phase contains the Treatment and Follow-up Periods. The Extension Phase will begin for subjects who received treatment in the study (either in the Treatment Period or Follow-up Period) at the time of database cutoff.

Conditions

KIF5B-RET-Positive Adenocarcinoma of the Lung

Keywords

KIF5B-RET-Positive Adenocarcinoma; Lung Cancer; NSCLC; Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  ORR was defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR), based on the investigator assessment of radiologic response according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. No independent review of tumor assessments was performed. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis to less than (\<) 10 millimeter (mm). PR was defined as at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum of diameters.

  From first dose date until PD, development of unacceptable toxicity, withdrawal of consent, participant's choice to stop study treatment (up to approximately 2 years 10 months)

Secondary Outcomes (3)

• Progression-free Survival (PFS)

  From first dose date until PD or death (up to approximately 2 years 10 months)

• Overall Survival (OS)

  From first dose date until date of death from any cause (approximately up to 2 years 10 months)

• Plasma Concentrations of Lenvatinib

  Cycle 1 Day 1: 0.5-4 hours, 6-10 hours postdose; Cycle 1 Day 15: predose, 0.5-4 hours, 6-10 hours postdose; Cycle 2 Day 1: predose, 2-12 hours postdose; Cycle 3 Day 1: predose; (Cycle length is equal to [=] 28 days)

Study Arms (1)

Lenvatinib

EXPERIMENTAL

Drug: Lenvatinib

Interventions

Lenvatinib DRUG

Starting dose of 24 mg orally, once per day

Also known as: E7080

Lenvatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must have a cytological or histological confirmed diagnosis of adenocarcinoma of the lung.
• Subject must be known to be RET positive (known KIF5B-RET translocation, or other confirmed RET translocations (e.g., CCDC6-RET)) or have an available tumor sample for local or central testing obtained prior to consent (Screen 1). Subjects whose samples need to be submitted for central laboratory testing must be current non-smokers and not known to have mutation in EGFR, KRAS, or ALK.
• Subjects may have received up to three prior systemic anticancer treatment regimens for adenocarcinoma of the lung (including adjuvant therapies and tyrosine-kinase inhibitors \[TKI\]), unless discussed with the sponsor.
• Subjects must have a clinically indicated need for systemic chemotherapy for adenocarcinoma of the lung based on the investigator's assessment
• Presence of measurable disease meeting the following criteria:
• At least one lesion of at least 1.0 cm in the long-axis diameter for a non-lymph node or at least 1.5 cm in the short-axis diameter for a lymph node which is serially measurable according to Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) using either computerized tomography (CT) or magnetic resonance imaging (MRI). If there is only one target lesion and it is a non-lymph node, it should have a longest diameter of at least 1.5 cm.
• Lesions previously treated with radiotherapy or locoregional therapy must show radiographic evidence of disease progression to be deemed a target lesion.
• Subjects with known brain metastases who have completed whole brain radiotherapy, stereotactic radiosurgery, or complete surgical resection will be eligible if they have remained clinically stable, asymptomatic and off of steroids for 28 days.
• Adequate bone marrow function, defined as:
• Absolute neutrophil count (ANC) greater than or equal to 1.5 x 10\^9/L (greater than or equal to 1500/mm\^3)
• Hemoglobin (Hb) greater than or equal 8.5 g/dL
• Platelet count greater than or equal 75 x 10\^9/L (greater than or equal 75,000/mm\^3)
• Adequate liver function, defined as:
• Bilirubin less than or equal 1.5 x upper limit of normal (ULN) except for unconjugated hyperbilirubinemia or Gilbert's syndrome
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) less than or equal 3 x ULN (less than or equal 5 x ULN if subject has liver metastases). If alkaline phosphatase is greater than 3 x ULN (in absence of liver metastases) or greater than 5 x ULN (in presence of liver metastases) AND the subject also is known to have bone metastases, the liver-specific alkaline phosphatase must be separated from the total and used to assess the liver function instead of total alkaline phosphatase.

You may not qualify if:

• Subjects who have received any anticancer therapy (including surgery, locoregional, biological, immunotherapy, hormonal, or radiotherapy) within 21 days before the first dose of study drug (28 days for investigational therapies).
• Subjects who have not recovered from toxicities as a result of prior anticancer therapy to less than Grade 2 severity per the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v4.0, except alopecia and infertility.
• Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction, or stroke within 6 months of the first dose of study drug, or cardiac arrhythmia requiring medical treatment at Screening.
• Gastrointestinal malabsorption or any other condition in the opinion of the investigator that might affect the absorption of lenvatinib.
• Active malignancy (except for adenocarcinoma of the lung or definitively treated melanoma in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix) within the past 24months.
• Major surgery within 3 weeks before the first dose of study drug.
• Bleeding or thrombotic disorders or use of anticoagulants such as warfarin or similar agents requiring therapeutic international normalized ratio (INR) monitoring. (Treatment with low molecular weight heparin is allowed.)
• Active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks before the first dose of study drug.
• Active infection (any infection requiring treatment).
• Symptomatic central nervous system (CNS) disease.
• Subjects having greater than 1+ proteinuria on urine dipstick testing will undergo 24-hour urine collection for quantitative assessment of proteinuria. Subjects with urine protein greater than or equal to 1 g/24-hour will be ineligible.
• Any medical or other condition that in the opinion of the investigator(s) would preclude the subject's participation in a clinical study or would preclude them from completing the study.
• Scheduled for surgery during the study.

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (23)

Unknown Facility

Duarte, California, United States

Location

Unknown Facility

La Jolla, California, United States

Location

Unknown Facility

Whittier, California, United States

Location

Unknown Facility

Jacksonville, Florida, United States

Location

Unknown Facility

Canton, Ohio, United States

Location

Unknown Facility

Cleveland, Ohio, United States

Location

Unknown Facility

Knoxville, Tennessee, United States

Location

Unknown Facility

Dallas, Texas, United States

Location

Unknown Facility

Hong Kong, Hong Kong

Location

Unknown Facility

Shatin, Hong Kong

Location

Unknown Facility

Nagoya, Aichi-ken, Japan

Location

Unknown Facility

Kashiwa, Chiba, Japan

Location

Unknown Facility

Akashi, Hyōgo, Japan

Location

Unknown Facility

Kobe, Hyōgo, Japan

Location

Unknown Facility

Natori-shi, Miyagi, Japan

Location

Unknown Facility

Ōsaka-sayama, Osaka, Japan

Location

Unknown Facility

Chuo-ku, Tokyo, Japan

Location

Unknown Facility

Koto-Ku, Tokyo, Japan

Location

Unknown Facility

Fukuoka, Japan

Location

National Cancer Center Hospital

Singapore, Singapore

Location

National University Hospital

Singapore, Singapore

Location

National Taiwan University Hospital

Taipei, Taiwan

Location

Veterans General Hospital Taipei

Taipei, Taiwan

Location

Related Publications (2)

• Hida T, Velcheti V, Reckamp KL, Nokihara H, Sachdev P, Kubota T, Nakada T, Dutcus CE, Ren M, Tamura T. A phase 2 study of lenvatinib in patients with RET fusion-positive lung adenocarcinoma. Lung Cancer. 2019 Dec;138:124-130. doi: 10.1016/j.lungcan.2019.09.011. Epub 2019 Sep 16.

  PMID: 31710864 DERIVED

• Wu H, Shih JY, Yang JC. Rapid Response to Sunitinib in a Patient with Lung Adenocarcinoma Harboring KIF5B-RET Fusion Gene. J Thorac Oncol. 2015 Sep;10(9):e95-e96. doi: 10.1097/JTO.0000000000000611. No abstract available.

  PMID: 26291023 DERIVED

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

lenvatinib

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Results Point of Contact

• Title: Eisai Medical Information
• Organization: Eisai Inc.

esi_oncmedinfo@eisai.com

1-888-274-2378

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2013
• First Posted: June 13, 2013
• Study Start: April 5, 2013
• Primary Completion: February 3, 2016
• Study Completion: November 2, 2017
• Last Updated: August 13, 2019
• Results First Posted: August 13, 2019

Record last verified: 2018-01

Locations

US (8); SG (2); TW (2); HK (2); JP (9)