Using Chronobiology to Improve Lenvatinib Efficacy

Early Phase 1

Recruiting

• Conditions: Lenvatinib Treatment
• Interventions: Drug: variability-based lenvatinib regimen

• Registration Number: NCT06321120
• Lead Sponsor: Hadassah Medical Organization

Brief Summary

The goal of this proof-of-concept clinical trial is to assess the efficacy and safety of chronobiology implementation into lenvatinib treatment regimens of thyroid cancer patients, via a mobile application.

Participants will use a mobile application to follow variability-based physician approved drug administration schedules.

Detailed Description

Systemic treatments for thyroid cancer have emerged in the past decade, accompanied by a deeper understanding of its underlying molecular mechanisms. Among these, lenvatinib, a multi-targeted tyrosine kinase inhibitor, was approved as a monotherapy for treating locally advanced or metastatic radioactive iodine refractory differentiated thyroid cancer. Despite its efficacy, lenvatinib is associated with a spectrum of adverse events (AEs), including hypertension, fatigue, proteinuria, and gastrointestinal disturbances, which often necessitate dose reduction, interruption, or permanent discontinuation. To overcome these challenges, the investigators address to the Constrained Disorder Principle (CDP), an innovative approach that emphasizes the exploration of constrained variability in treatment regimens to optimize drug effectiveness and minimize AEs. In other disease contexts, such as congestive heart failure, multiple sclerosis, and chronic pain, the integration of CDP-based second-generation artificial intelligence (AI) systems into treatment regimens has shown promising results in enhancing therapeutic outcomes by dynamically adjusting treatment parameters. The investigators hypothesize that a personalized dynamic adjustment of lenvatinib dosages and administration timing, guided by an AI-driven approach via a mobile application, may reduce AEs, improve adherence, and enhance overall treatment efficacy. In this proof-of-concept study, the investigators aim to evaluate the feasibility and efficacy of utilizing a CDP-based second-generation AI system to optimize the therapeutic regimen of lenvatinib in patients with cancer.

Study Timeline

• Study Start: 2023-03-01
• Status Verified: 2024-03
• Study First Submitted: 2024-03-11
• Study First Submitted QC: 2024-03-17
• Last Update Submitted: 2024-03-17
• Study First Posted: 2024-03-20
• Last Update Posted: 2024-03-20
• Primary Completion: 2024-04
• Study Completion: 2024-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

1. Age 18-80 years
2. Lenvatinib treated cancer patients, who suffer from loss of response of dose-limiting adverse effects.

Exclusion Criteria

1. Current or history of drug abuse
2. Pregnancy/lactation/planned pregnancy
3. The subject is currently enrolled in or has not yet completed at least 60 days since ending another investigational device or drug trial.
4. Unable to comply with study requirements.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Variability-based lenvatinib treatment	variability-based lenvatinib regimen	Dosages and administration times were tailored within individual predefined ranges to accommodate personalized therapeutic regimens. The first level of the algorithm, employed in the present study, utilizes a pseudo-random number generator to select dosages and administration times from the ranges stipulated by the physician.

Primary Outcome Measures

Name	Time	Method
disease progression/ tumor response	at enrollment and at study completion (14 weeks later)	tumor response according to positron emission tomography-computed tomography (PET-CT) and tumor markers (thyroglobulin)

Secondary Outcome Measures

Name	Time	Method
Adverse effects occurrence	Blood tests will be drawn at enrollment and at study completion (14 weeks later). Telephone check-ups will be conducted monthly during the follow-up.	Safety assessments are performed throughout the study and include the recording of symptoms and emergency room visits or hospitalizations through a regular monthly telephone check-up and a hospital and ambulatory medical records review. Additionally, patients can report AEs online via the application. Hematological and biochemical laboratory testing, urinalysis, and self-conducted home blood pressure monitoring are also executed.

Trial Locations

Locations (1)

Hadassah Medical Organization; 🇮🇱 Jerusalem, Israel