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

Phase 2

Completed

• Conditions: KIF5B-RET-Positive Adenocarcinoma of the Lung

• Registration Number: JPRN-jRCT2080222692
• Lead Sponsor: Eisai Co., Ltd.

Brief Summary

This study indicates that lenvatinib demonstrated activity in patients with RET fusion-positive lung adenocarcinomas. Overall, lenvatinib therapy resulted in manageable tolerability, with no new safety signals detected.

Detailed Description

Not available

Study Timeline

• Study Start: 2014-12-12
• Results First Posted: 2015-09-01
• Study Completion: 2018-03-22
• Last Update Posted: 17 October 2023

Recruitment & Eligibility

• Status: completed
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

1.Subjects must have a cytological or histological confirmed diagnosis of adenocarcinoma of the lung.
2.Subjects must have tumors expressing the KIF5B-RET translocation as detected by gene sequencing, or other confirmed RET translocations (e.g., CCDC6-RET).
3.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.
4.Subjects must have a clinically indicated need for systemic chemotherapy for adenocarcinoma of the lung based on the investigator's assessment
5.Presence of measurable disease meeting the following criteria:
a.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.
b.Lesions previously treated with radiotherapy or locoregional therapy must show radiographic evidence of disease progression to be deemed a target lesion.
6.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.
7.Adequate bone marrow function, defined as:
a.Absolute neutrophil count (ANC) greater than or equal to 1.5 x 109(10 to the ninth power) /L (greater than or equal to 1500/mm3)
b.Hemoglobin (Hb) greater than or equal 8.5 g/dL
c.Platelet count greater than or equal 75 x 109(10 to the ninth power) /L (greater than or equal 75,000/mm3)
8.Adequate liver function, defined as:
a.Bilirubin less than or equal 1.5 x upper limit of normal (ULN) except for unconjugated hyperbilirubinemia or Gilbert's syndrome
b.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.
9.Adequate renal function, defined as calculated creatinine clearance greater than 40 mL/min per the Cockcroft and Gault formula.
10.Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP less than 150/90 mmHg at screening and no change in antihypertensive medications within 1 week before Cycle 1/Day 1 (C1D1).
11.Eastern Cooperative Oncology Group (ECOG)-Performance Status (PS) of 0 or 1.
12.Survival expectation of 12 weeks or longer after starting study drug.
13.Males or females aged at least 18 years (or any age greater than 18 years as determined by country legislation) at the time of informed consent (Screen 1).
14.Females must not be breast-feeding or pregnant at Screening or Baseline (as documented by a negative beta-human chorionic gonadotropin [B-hCG] test with a minimum sensitivity of 25 IU/L or equivalent units of B-hCG). A separate baseline assessment

Exclusion Criteria

1.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).
2.Leptomeningeal metastases or brain metastases except as for Inclusion Criterion #6.
3.Subjects who have not recovered from toxicities as a result of prior anticancer therapy to < Grade 2 severity per the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v4.0, except alopecia and infertility.
4.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.
5.Gastrointestinal malabsorption or any other condition in the opinion of the investigator that might affect the absorption of lenvatinib.
6.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.
7.Major surgery within 3 weeks before the first dose of study drug.
8.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.)
9.Active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks before the first dose of study drug.
10.Active infection (any infection requiring treatment).
11.Symptomatic central nervous system (CNS) disease.
12.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.
13.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.
14.Scheduled for surgery during the study.

Study & Design

• Study Type: Interventional
• Study Design: Not specified