Gender-based Impact on Safety and Efficacy of Lenvatinib in Patients With Differentiated Thyroid Cancer (Gisel)

Observational Study on Gender-based Impact on Safety and Efficacy of Lenvatinib in Patients With Radioiodine Refractory Differentiated Thyroid Cancer

Lenvatinib is approved for the treatment of radioiodine refractory differentiated thyroid cancer. Despite gender can play a crucial role un in safety and efficacy of oncological product, little is know on gender difference in lenvatinb effacacy and safety in the context of radioiodine refractory differentiated thyroid cancer.

The primary objective of the study is to assess safety and toxicity profile in male and female patients in terms of dose reduction. The secondary objectives are to assess sex and gender difference in: the number and the incidence of adverse events; response rate according to RECIST criteria 1.1; progression free survival, overall survival and duration of response.

Study Overview

• Status: Recruiting
• Conditions: Differentiated Thyroid Cancer; Gender
• Intervention / Treatment: Drug: Lenvatinib

Detailed Description

Lenvatinib is an orally available potent inhibitor of the split-kinase family of transmembrane growth factor receptors including Flt-1/VEGFR-1 and KDR/VEGFR. Lenvatinib has been investigated in hepatocellular carcinoma and in RAI-resistant thyroid cancer (Phase III trials) and in other malignancies, showing high rates of activity. In RAI-resistant thyroid cancer, lenvatinib showed a remarkable response rate over placebo (65% vs 2), combined with a prolonged progression free survival (18.3 vs 3.6 months). It has been approved for the treatment of locally recurrent or metastatic, progressive RAI resistance-DTC in the United States, Europe, and Japan, based on the results from SELECT trial. Moreover, lenvatinib demonstrated a meaningful clinical activity (response rate 64.8% in treatment arm vs 1.5% in placebo arm, p<0.001;) significantly reducing the tumour burden, with a median maximum percentage change in tumour size of -42.9%. Response was mostly pronounced at the first assessment (median -24.7% at 8 weeks after randomization) but it has been observed even in the following months (-1.3% per month). Recently, the efficacy of lenvatinib was confirmed in specific patient population, such as elderly. Although the efficacy is remarkable toxic effects are considerable and not all patients have the same risk to benefit ratio from lenvatinib treatment. Results derived from controlled clinical trials are rarely replicable in the real-life because these trials are usually conducted in selected populations, in a highly controlled setting, optimized to show the effect of the drug.

In this context growing evidences are showing gender associated functions playing a role in cancer incidence, progression and response to therapy; gender disparities in toxicities and effectiveness of certain drugs used in the treatment of the most common cancer is already well known.The aim of the present study is to evaluate the safety and efficacy profile of Lenvatinib based on gender in patients with refractory iodine DTC.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Marialuisa Appetecchia, Prof; Phone Number: 00390652666026; Email: marialuisa.appetecchia@ifo.it

Study Locations

• Italy
  • Rome, Italy, 00144
    • Recruiting
    • Regina Elena National Cancer Institute
    • Contact: Marialuisa Appetecchia, MD; Phone Number: 0039 0652666026; Email: marialuisa.appetecchia@ifo.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients affected by radio-refractory iodine differentiated thyroid cancer

Description

Inclusion Criteria:

• Patients with refractory iodine DTC treated with lenvatinib
• Signed written informed consent

Exclusion Criteria:

- Age < 18 years

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gender difference in Safety profile of lenvatinib treatment	Difference in lenvatinib dose reduction between male and female patients	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gender difference in lenvatinib side effects incidence	Difference in number of lenvatinib side effects between male and female patients according to CTCAE 5.0	1 year
Gender difference in lenvatinib response rate	Difference in lenvatinib response rate (CR+PR) according to RECIST response evaluation criteria 1.1 in male and female patients.	1 year
Gender difference progression free survival and overall survival of patients treated with lenvatinib	Difference in progression free survival and overall survival of patients treated with lenvatinib in male and female patients.	1 year

Collaborators and Investigators

• Sponsor: Regina Elena Cancer Institute
• Collaborators: University of Pisa; University of Roma La Sapienza; University of Turin, Italy; Istituto Oncologico Veneto IRCCS; University of Catania; Istituto Auxologico Italiano; University of Siena
• Investigators: Principal Investigator: Marialuisa Appetecchia, Prof, Regina Elena Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): May 27, 2020
• Primary Completion (Estimated): July 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: March 16, 2023
• First Submitted That Met QC Criteria: March 16, 2023
• First Posted (Actual): March 29, 2023

Study Record Updates

• Last Update Posted (Actual): April 10, 2024
• Last Update Submitted That Met QC Criteria: April 9, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Endocrine System Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Thyroid Diseases; Thyroid Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Lenvatinib
• Other Study ID Numbers: RS1316/20(2312)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Raw data will be published in open access database
• IPD Sharing Time Frame: At the end of the study
• IPD Sharing Access Criteria: Open access

Drug and device information, study documents

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