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

NCT04858867 | Unknown DMC

• 1 other identifier: P20.096
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Differentiated Thyroid Cancer

Outcome Measures

Primary Outcomes (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.

  2-3 months after completed inclusion of all study participants

Secondary Outcomes (13)

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

  0, 6, 12 weeks after inclusion

• Optimal duration of lenvatinib treatment for maximum redifferentiation to occur

  3 months after completed inclusion of cohort 1

• Extent of RAI uptake after I-131 therapy

  7 or 12 weeks after inclusion

• Metabolic treatment response using F-18 FDG PET

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

• Unstimulated (TSH suppressed) thyroglobulin levels

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

Other Outcomes (1)

• NIS expression in biopted tumor lesion(s) at baseline and 6 weeks after lenvatinib

  0 and 6 weeks after inclusion

Study Arms (2)

Cohort 1

OTHER

Study 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

Radiation: rhTSH-stimulated I-124 dosimetry; Radiation: Intra-therapeutic I-131 dosimetry

Cohort 2

OTHER

Study 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

Radiation: rhTSH-stimulated I-124 dosimetry; Radiation: Intra-therapeutic I-131 dosimetry

Interventions

rhTSH-stimulated I-124 dosimetry RADIATION

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

Cohort 1; Cohort 2

Intra-therapeutic I-131 dosimetry RADIATION

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

Cohort 1; Cohort 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Leiden University Medical Center: lead

Study Sites (1)

Leiden University Medical Center

Leiden, South Holland, 2333ZA, Netherlands

RECRUITING

Related Publications (2)

• 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.

  PMID: 32744039 BACKGROUND

• 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.

  PMID: 36553163 BACKGROUND

Study Officials

• Ellen Kapiteijn, MD, PhD

  LUMC

  PRINCIPAL INVESTIGATOR

• Dennis Vriens, MD, PhD

  LUMC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Maaike Dotinga, MSc

CONTACT

+31715263695; M.Dotinga@lumc.nl

Dennis Vriens, MD, PhD

CONTACT

+31715299703; D.Vriens@lumc.nl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Oncologist, Associate Professor Research and Treatment of Rare Cancers

Study Record Dates

• First Submitted: April 9, 2021
• First Posted: April 26, 2021
• Study Start: January 10, 2022
• Primary Completion: January 1, 2025
• Study Completion: June 1, 2025
• Last Updated: October 10, 2023

Record last verified: 2023-10

Locations

NL (1)