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Differentiated Thyroid CancerRESETNCT04858867

Reinducing Radioiodine-sensitivity in Radioiodine-refractory DTC Using Lenvatinib (RESET)

A study testing rhTSH-stimulated I-124 dosimetry and Intra-therapeutic I-131 dosimetry in people with Differentiated Thyroid Cancer, run by Leiden University Medical Center at 1 site in Netherlands.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

This is a single-centre open label phase II study evaluating the effect of lenvatinib treatment for restoring radioiodine uptake and retention in radioiodine-refractory (RAI-R) thyroid cancer to warrant I-131 therapy. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Differentiated Thyroid Cancer
What is being tested?
rhTSH-stimulated I-124 dosimetry and Intra-therapeutic I-131 dosimetry
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
1 siteNetherlands
Study dates
10 Jan 2022to 1 Jun 2025
Phase
Interventional
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age ≥ 18 years at the time of informed consent
  • Histologically or cytologically confirmed DTC (including papillary, follicular or Hürthle Cell carcinoma)
  • Progressive (biochemical or anatomic) disease for which lenvatinib is started as standard treatment at the discretion of the treating physician
  • Measurable disease at baseline imaging (F-18 FDG PET) according to the definition of the Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) 1.0 with at least one lesion ≥1.0 cm in the longest diameter for a non-lymph node or ≥1.5 cm in the short axis for a lymph node.
  • RAI-R disease on structural imaging, defined as any one of the following:
  • Metastatic lesions that are not RAI-avid on a diagnostic or intra-therapeutic RAI scanperformed prior to enrolment in the current study
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  • RAI-avid metastatic lesions which remained stable in size or progressed according to RECIST 1.1 criteria despite RAI treatment. Absence of response is observed during 6-9 months after high dose I-131 therapy.
  • No recent treatment for thyroid cancer:
  • No prior I-131 therapy is allowed <6 months prior to initiation of therapy on this protocol (a diagnostic study using <400 MBq of I-131 is not considered 131I therapy)
  • No external beam radiation therapy is allowed <4 weeks prior to initiation of therapy on this protocol. (Previous treatment with radiation for any indication is allowed if the investigator judges that the previous radiation does not significantly compromise patient safety on this protocol)
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤2 (or Karnofsky ≥60%)
  • Life expectancy ≥3 months
  • Ability to swallow and retain orally-administered medication and no clinically significant gastrointestinal abnormalities that may alter absorption
  • Creatinine ≤1.5 mg/dL (≤133 µmol/L) or estimated glomerular filtration rate (eGFR) (using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula) ≥50 mL/min/1.73m2 or 24-hour urine creatinine clearance ≥50 mL/min/1.73m2
  • Adequate blood coagulation function as evidenced by an international normalized ratio (INR) ≤1.5
  • Adequate bone marrow function with:
  • Absolute neutrophil count ≥1.5*10^9 /L
  • Hemoglobin ≥9 g/dL (5.6 mmol/L)
  • Platelets ≥100*10^9 /L
  • Adequate liver function with
  • Albumin ≥25 g/L
  • Total bilirubin <1.5x institutional upper limit of normal (ULN) with an exception for patients with Gilbert's syndrome
  • Aspartate aminotransferase and alanine aminotransferase ≤3x institutional ULN (≤5x ULN if subject has liver metastases)
  • Negative pregnancy test within 7 days prior to starting the study for premenopausal women. Women can be included without pregnancy test if they are either surgically sterile or have been postmenopausal for ≥1 year.
  • Sexually active women of childbearing potential must agree to use a highly effective method of contraception during the study and for at least 6 months after the last study treatment administration.Sexually active males patients must agree to use condom during the study and for at least 6 months after the last study treatment administration. Also, it is recommended their women of childbearing potential partner use a highly effective method of contraception. Effective methods of contraception are defined as those, which result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly (for example implants, injectables, combined oral contraception or intrauterine devices). At the discretion of the investigator, acceptable methods of contraception may include total abstinence in cases where the lifestyle of the patient ensures compliance. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable methods of contraception.)
  • Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol

Who cannot join

  • Concomitant or previous malignancies within the last 3 years. Patients are eligible for this study if they have been disease-free of the previous malignancy for at least 3 years, have a history of completely resected non-melanoma skin cancer and/or have indolent secondary malignancies.
  • Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression
  • Evidence of cardiovascular risk including any of the following:
  • Clinically relevant arrhythmias
  • Acute coronary syndromes, severe/unstable angina
  • Symptomatic congestive heart failure
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  • Use of other investigational drugs within 28 days preceding the first dose of treatment in this study or during the study
  • Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to lenvatinib and/or to Thyrotropin alfa (human recombinant thyrotropin) or other known contents of the two drugs.
  • Inability to follow a low iodine diet or requiring medication with high content in iodide (e.g. amiodarone)
  • Patients who received iodinated intravenous contrast as part of a radiographic procedure within 6-8 weeks of study registration. Patients are eligible for this study if urinary iodine analysis reveals that the excess iodine has been adequately cleared after the last intravenous contrast administration
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant, lactating or breast feeding women
  • Any medical or other condition that in the opinion of the investigator(s) would preclude the participation in a clinical study
  • Unwillingness or inability to comply with study and follow-up procedures

Trial locations and contacts

1 site in 1 country.

Maaike Dotinga, MSc contact

+31715263695

M.Dotinga@lumc.nl

Dennis Vriens, MD, PhD contact

+31715299703

D.Vriens@lumc.nl

Netherlands1 site, 1 recruiting

  • Leiden University Medical Center

    Leiden, South Holland, 2333ZA

    Ellen Kapiteijn, MD, PhD, +31715263206, H.W.Kapiteijn@lumc.nl

    Maaike Dotinga, MSc, +31715263695, M.Dotinga@lumc.nl

    Recruiting

Other trials in Netherlands

About this study

Official title: Reinducing Radioiodine-sensitivity in Radioiodine-refractory Differentiated Thyroid Cancer Using Lenvatinib (RESET)

This is a single-centre open label phase II study evaluating the effect of lenvatinib treatment for restoring radioiodine uptake and retention in radioiodine-refractory (RAI-R) thyroid cancer to warrant I-131 therapy.

Read the detailed description

RAI-R DTC patients starting standard-of-care lenvatinib treatment will be included in this study. Prior to lenvatinib treatment, patients will undergo I-124 PET/CT to quantify RAI uptake and retention at baseline. The first half of the intended sample size (cohort 1) will be treated with lenvatinib for a total of 12 weeks. After 6- and 12-week treatment, patients will undergo I-124 PET/CT dosimetry to evaluate the redifferentiation effect, assess expected absorbed lesion doses and maximum tolerable activity. Results between 6- and 12-week lenvatinib treatment will be compared to select the lenvatinib treatment duration that leads to highest extent of redifferentiation. The next patients (cohort 2) will then receive lenvatinib for either 6 or 12 weeks.

Patients will undergo subsequent I-131 therapy if a clinically meaningful lesion dose is expected and toxicity is deemed acceptable. For all patients eligible for I-131 therapy, lenvatinib is discontinued prior to administration of I-131 and intra-therapeutic I-131 SPECT dosimetry will be performed for dose verification. Patients who are not eligible for I-131 therapy, will continue lenvatinib treatment at the discretion of the treating physician.

Biopsies are performed at baseline and after 6-week lenvatinib treatment to evaluate alterations at the transcriptional and translational level in biopted tumor lesions. Patients will be followed up according to current guidelines for a total of 9 months after initiating lenvatinib treatment. Metabolic and biochemical response will be assessed using F-18 FDG PET/CT and Tg levels, respectively.

Being tested
rhTSH-stimulated I-124 dosimetry, Intra-therapeutic I-131 dosimetry

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • rhTSH-stimulated I-124 dosimetryRadiation

    Preparation:

    • Low iodine diet 7 days prior to I-124 ingestion until 24 hours post-ingestion
    • Thyrogen injections 24 and 48h prior to I-124 ingestion

    Procedures following Jentzen et al:

    • Ingestion of capsule with 37±10% MBq I-124
    • I-124 PET/CT at 24 and 96h post-ingestion
    • Blood draws at 2, 24 and 96h post-ingestion
    • Whole body counting at 2, 24 and 96h post-ingestion

  • Intra-therapeutic I-131 dosimetryRadiation

    Procedures following EANM guidelines:

    • I-131 SPECT/CT at 2, 6, 24, 96 and 144h post-ingestion
    • Blood draws at 2, 6, 24, 96 and 144h post-ingestion
    • Whole body counting at 2, 6, 24, 96 and 144h post-ingestion
Study groups in NCT04858867
Study groupRoleWhat they receive
Cohort 1OtherStudy procedures * Lenvatinib during week 1-12 * rhTSH-stimulated I-124 dosimetry at week 0, 6 and 12 * rhTSH-stimulated I-131 therapy at week 13 (if eligible) * Intra-therapeutic I-131 dosimetry at week 13 (if eligible) * Biopsy at week 0 and 6 * F-18 FDG PET/CT at week 0, 6, 12, 24 and 36 * Tg levels at week 0, 6, 12, 24 and 36 * QoL assessment at week 0, 6, 12, 24 and 36
Receives: Radiation: rhTSH-stimulated I-124 dosimetry; Radiation: Intra-therapeutic I-131 dosimetry
Cohort 2OtherStudy procedures (in case of 12-wk lenvatinib): * Lenvatinib during week 1-12 * rhTSH-stimulated I-124 dosimetry at week 0 and 12 * rhTSH-stimulated I-131 therapy at week 13 (if eligible) * Intra-therapeutic I-131 dosimetry at week 13 (if eligible) * Biopsy at week 0 and 6 * F-18 FDG PET/CT at week 0, 12, 24 and 36 * Tg levels at week 0, 6, 12, 24 and 36 * QoL assessment at week 0, 6, 12, 24 and 36 Study procedures (in case of 6-wk lenvatinib) * Lenvatinib during week 1-6 * rhTSH-stimulated I-124 dosimetry at week 0 and 6 * rhTSH-stimulated I-131 therapy at week 13 (if eligible) * Intra-therapeutic I-131 dosimetry at week 13 (if eligible) * Biopsy at week 0 and 6 * F-18 FDG PET/CT at week 0, 6, 12, 24, 30 and 36 * Tg levels at week 0, 6, 12, 24, 30 and 36 * QoL assessment at week 0, 6, 12, 24, 30 and 36
Receives: Radiation: rhTSH-stimulated I-124 dosimetry; Radiation: Intra-therapeutic I-131 dosimetry

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Fraction of RAI-R thyroid cancer patients who are eligible for I-131 therapy after 6- or 12-week lenvatinib treatment

    Patients are deemed eligible for I-131 therapy if the therapeutic activity (max. 7.4 GBq) will lead to (1) an expected absorbed dose >20 Gy in at least one lesion, (2) a blood dose <2 Gy and (3) whole body retention <3.0 or 4.4 GBq at 48h post-ingestion in presence or absence of diffuse pulmonary metastases, respectively.

    Measured: 2-3 months after completed inclusion of all study participants

Secondary outcomes (13)

  1. Extent of RAI uptake at baseline and after 6- or 12-week lenvatinib

    Assessing expected absorbed dose [Gy] per lesion or critical organ using I-124 PET/CT, whole body counting and blood sampling

    Measured: 0, 6, 12 weeks after inclusion

  2. Optimal duration of lenvatinib treatment for maximum redifferentiation to occur

    Either 6 of 12 weeks after comparing (1) fraction of patients eligible for I-131 therapy, (2) expected absorbed dose [Gy] per lesion or critical organ and (3) toxicity incidence and severity

    Measured: 3 months after completed inclusion of cohort 1

  3. Extent of RAI uptake after I-131 therapy

    Assessing expected absorbed dose [Gy] per lesion or critical organ using intra-therapeutic I-131 SPECT/CT, whole body counting and blood sampling

    Measured: 7 or 12 weeks after inclusion

  4. Metabolic treatment response using F-18 FDG PET

    Metabolic response will be assessed using PERCIST v1.0. Tumor response is defined as complete response, partial response, stable response or progressive disease.

    Measured: 0, 6, 12, 24, 30, 36 weeks after inclusion

  5. Unstimulated (TSH suppressed) thyroglobulin levels

    Assessment of biochemical treatment response

    Measured: 0, 6, 12, 24, 30, 36 weeks after inclusion

  6. Overall survival at 36 weeks after initation of lenvatinib

    Measured: 9 months after inclusion

  7. Best objective response at 36 weeks after initation of lenvatinib

    Measured: 9 months after inclusion

  8. Progression free survival at 36 weeks after initation of lenvatinib

    Measured: 9 months after inclusion

  9. Incidence and severity of toxicities according to CTCAE 5.0

    Measured: during 0-9 months after inclusion

  10. Quality of life using standardized questionnaire ThycaQoL

    Measured: 0, 6, 12, 24, 30, 36 weeks after inclusion

  11. Quality of life using standardized questionnaire RAND36

    Measured: 0, 6, 12, 24, 30, 36 weeks after inclusion

  12. Quality of life using standardized questionnaire EQ5D5L

    Measured: 0, 6, 12, 24, 30, 36 weeks after inclusion

  13. Quality of life using standardized questionnaire Distress thermometer

    Measured: 0, 6, 12, 24, 30, 36 weeks after inclusion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Apr 2021
  2. Study start10 Jan 2022
  3. Primary completion1 Jan 2025 (estimated)
  4. Study completion1 Jun 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
12 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04858867
Sponsor's protocol ID
P20.096
Acronym
RESET
Status last verified
Oct 2023
First submitted
9 Apr 2021
Last updated
10 Oct 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Dotinga M, Vriens D, van Velden F, Heijmen L, Nagarajah J, Hicks R, Kapiteijn E, de Geus-Oei LF. Managing radioiodine refractory thyroid cancer: the role of dosimetry and redifferentiation on subsequent I-131 therapy. Q J Nucl Med Mol Imaging. 2020 Sep;64(3):250-264. doi: 10.23736/S1824-4785.20.03264-1.

    PubMed 32744039

  • Dotinga M, Vriens D, van Velden FHP, Stam MK, Heemskerk JWT, Dibbets-Schneider P, Pool M, Rietbergen DDD, de Geus-Oei LF, Kapiteijn E. Reinducing Radioiodine-Sensitivity in Radioiodine-Refractory Thyroid Cancer Using Lenvatinib (RESET): Study Protocol for a Single-Center, Open Label Phase II Trial. Diagnostics (Basel). 2022 Dec 14;12(12):3154. doi: 10.3390/diagnostics12123154.

    PubMed 36553163

Questions about this trial

What is this clinical trial studying?

A study testing rhTSH-stimulated I-124 dosimetry and Intra-therapeutic I-131 dosimetry in people with Differentiated Thyroid Cancer, run by Leiden University Medical Center at 1 site in Netherlands.

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 26 inclusion and 14 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 10 Oct 2023. 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 Netherlands. 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.

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 Maaike Dotinga, MSc (+31715263695, M.Dotinga@lumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Fraction of RAI-R thyroid cancer patients who are eligible for I-131 therapy after 6- or 12-week lenvatinib treatment (time frame: 2-3 months after completed inclusion of all study participants). 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 NCT04858867, which also lists 2 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 10 Oct 2023.

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