Lenvatinib TreatmentEarly Phase 1NCT06321120
Using Chronobiology to Improve Lenvatinib Efficacy
A Early Phase 1 study testing variability-based lenvatinib regimen in people with Lenvatinib Treatment, run by Hadassah Medical Organization at 1 site in Israel.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Lenvatinib Treatment
- What is being tested?
- variability-based lenvatinib regimen
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteIsrael
- Study dates
- 1 Mar 2023to Jun 2024
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18-80 years
- Lenvatinib treated cancer patients, who suffer from loss of response of dose-limiting adverse effects.
Who cannot join
- Current or history of drug abuse
- Pregnancy/lactation/planned pregnancy
- The subject is currently enrolled in or has not yet completed at least 60 days since ending another investigational device or drug trial.
- Unable to comply with study requirements.
Trial locations and contacts
1 site in 1 country.
Israel1 site, 1 recruiting
- Recruiting
Hadassah Medical Organization
Jerusalem, 91120
Hadas Lemberg, PhD, +97226777572, lhadas@hadassah.org.il
About this study
Official title: A Controlled Trial for Improving the Response to Lenvatinib in Patients With Drug-resistant Thyroid Cancer by Chronobiology
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.
Read the 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.
- Conditions
- Lenvatinib Treatment
- Being tested
- variability-based lenvatinib regimen
- Keywords
- cancer, lenvatinib, constrained disorder principle, digital pill
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
variability-based lenvatinib regimenDrug
Dosages and administration times were tailored within individual predefined ranges to accommodate personalized therapeutic regimens. As per protocol, the daily dose was limited to match or remain below the patients' pre-enrollment dosage level. In the initial 4 weeks of the follow-up, participants followed a fixed standard regimen with the app serving as a reminder, allowing for an adaptation period. Subsequently, the algorithm-driven treatment plan was implemented for an additional 10 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Variability-based lenvatinib treatment | Experimental | 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. Receives: Drug: variability-based lenvatinib regimen |
What is being measured
The primary outcome is the main question the study is designed to answer.
disease progression/ tumor response
tumor response according to positron emission tomography-computed tomography (PET-CT) and tumor markers (thyroglobulin)
Measured: at enrollment and at study completion (14 weeks later)
Secondary outcomes (1)
Adverse effects occurrence
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.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2024
- Study start1 Mar 2023
- Primary completionApr 2024 (estimated)
- Study completionJun 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Lenvatinib TreatmentStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- An open-labeled, prospective, single-center proof-of-concept clinical trial lasting 14 weeks was conducted to investigate the impact of an algorithm-based regimen on enhancing lenvatinib effectiveness.
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hadassah Medical Organization
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06321120
- Sponsor's protocol ID
- 0749-21-HMO-CTIL
- Status last verified
- Mar 2024
- First submitted
- 11 Mar 2024
- Last updated
- 20 Mar 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: irrelevant
Publications
Schlumberger M, Tahara M, Wirth LJ, Robinson B, Brose MS, Elisei R, Habra MA, Newbold K, Shah MH, Hoff AO, Gianoukakis AG, Kiyota N, Taylor MH, Kim SB, Krzyzanowska MK, Dutcus CE, de las Heras B, Zhu J, Sherman SI. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med. 2015 Feb 12;372(7):621-30. doi: 10.1056/NEJMoa1406470.
PubMed 25671254Gelman R, Hurvitz N, Nesserat R, Kolben Y, Nachman D, Jamil K, Agus S, Asleh R, Amir O, Berg M, Ilan Y. A second-generation artificial intelligence-based therapeutic regimen improves diuretic resistance in heart failure: Results of a feasibility open-labeled clinical trial. Biomed Pharmacother. 2023 May;161:114334. doi: 10.1016/j.biopha.2023.114334. Epub 2023 Mar 9.
PubMed 36905809Ilan Y. Overcoming Compensatory Mechanisms toward Chronic Drug Administration to Ensure Long-Term, Sustainable Beneficial Effects. Mol Ther Methods Clin Dev. 2020 Jun 10;18:335-344. doi: 10.1016/j.omtm.2020.06.006. eCollection 2020 Sep 11.
PubMed 32671136Ilan Y, Spigelman Z. Establishing patient-tailored variability-based paradigms for anti-cancer therapy: Using the inherent trajectories which underlie cancer for overcoming drug resistance. Cancer Treat Res Commun. 2020;25:100240. doi: 10.1016/j.ctarc.2020.100240. Epub 2020 Nov 19.
PubMed 33246316
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Controlled Trial for Improving the Response to Lenvatinib in Patients With Drug-resistant Thyroid Cancer by Chronobiology
- ClinicalTrials.gov ID
- NCT06321120
- Acronym / sponsor ID
- 0749-21-HMO-CTIL
- Conditions
- Lenvatinib Treatment
- Keywords
- cancer, lenvatinib, constrained disorder principle, digital pill
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Hadassah Medical OrganizationUniversity, hospital or other
- Study start
- 1 Mar 2023 (actual)
- Primary completion
- Apr 2024 (estimated)
- Study completion
- Jun 2024 (estimated)
- First posted
- 20 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- An open-labeled, prospective, single-center proof-of-concept clinical trial lasting 14 weeks was conducted to investigate the impact of an algorithm-based regimen on enhancing lenvatinib effectiveness.
| Arm | Type | Receives |
|---|---|---|
| Variability-based lenvatinib treatment | Experimental | Drug: variability-based lenvatinib regimenDosages 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Age 18-80 years
- Lenvatinib treated cancer patients, who suffer from loss of response of dose-limiting adverse effects.
Key exclusion criteria (4 listed)
- Current or history of drug abuse
- Pregnancy/lactation/planned pregnancy
- The subject is currently enrolled in or has not yet completed at least 60 days since ending another investigational device or drug trial.
- Unable to comply with study requirements.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| variability-based lenvatinib regimenDosages and administration times were tailored within individual predefined ranges to accommodate personalized therapeutic regimens. As per protocol, the daily dose was limited to match or remain below the patients' pre-enrollment dosage level. In the initial 4 weeks of the follow-up, participants followed a fixed standard regimen with the app serving as a reminder, allowing for an adaptation period. Subsequently, the algorithm-driven treatment plan was implemented for an additional 10 weeks. | Drug | Variability-based lenvatinib treatment |
Primary outcome
disease progression/ tumor response
Time frame: at enrollment and at study completion (14 weeks later)
tumor response according to positron emission tomography-computed tomography (PET-CT) and tumor markers (thyroglobulin)
1 secondary outcome
Adverse effects occurrence
Time frame: 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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2024.
- Background: PubMed 25671254Schlumberger M, Tahara M, Wirth LJ, Robinson B, Brose MS, Elisei R, Habra MA, Newbold K, Shah MH, Hoff AO, Gianoukakis AG, Kiyota N, Taylor MH, Kim SB, Krzyzanowska MK, Dutcus CE, de las Heras B, Zhu J, Sherman SI. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med. 2015 Feb 12;372(7):621-30. doi: 10.1056/NEJMoa1406470.
- Background: PubMed 36905809Gelman R, Hurvitz N, Nesserat R, Kolben Y, Nachman D, Jamil K, Agus S, Asleh R, Amir O, Berg M, Ilan Y. A second-generation artificial intelligence-based therapeutic regimen improves diuretic resistance in heart failure: Results of a feasibility open-labeled clinical trial. Biomed Pharmacother. 2023 May;161:114334. doi: 10.1016/j.biopha.2023.114334. Epub 2023 Mar 9.
- Background: PubMed 32671136Ilan Y. Overcoming Compensatory Mechanisms toward Chronic Drug Administration to Ensure Long-Term, Sustainable Beneficial Effects. Mol Ther Methods Clin Dev. 2020 Jun 10;18:335-344. doi: 10.1016/j.omtm.2020.06.006. eCollection 2020 Sep 11.
- Background: PubMed 33246316Ilan Y, Spigelman Z. Establishing patient-tailored variability-based paradigms for anti-cancer therapy: Using the inherent trajectories which underlie cancer for overcoming drug resistance. Cancer Treat Res Commun. 2020;25:100240. doi: 10.1016/j.ctarc.2020.100240. Epub 2020 Nov 19.
- Individual participant dataSharing planned: No. irrelevant
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing variability-based lenvatinib regimen in people with Lenvatinib Treatment, run by Hadassah Medical Organization at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 20 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Aharon Popovtzer, MD (972509010225, ARON@HADASSAH.ORG.IL), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
disease progression/ tumor response (time frame: at enrollment and at study completion (14 weeks later)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06321120, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2024.