Cabozantinib In Advanced Radioactive-Iodine Refractory Differentiated Thyroid Cancer.

NCT05660954 | Completed Phase 2

• 1 other identifier: GETNE-T2216
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 9

Brief Summary

CABOTHYROID is a prospective, exploratory, biomarker-focused, phase II, single-arm, non-randomized, non-blinded, investigator-initiated study of cabozantinib in patients with previously treated advanced radioactive-iodine refractory

Conditions

Differentiated Thyroid Cancer

Keywords

Cancer; Thyroid; Cabozantinib

Outcome Measures

Primary Outcomes (2)

• Gene expression of molecular biomarkers characteristics of the pathology

  Gene expression levels in the sample will be reported as media and interquartile range for each one of the biomarkers included in the determination. Determination of the expression of the molecular markers will perform applied chromatin immunoprecipitation of cell-free nucleosomes carrying active chromatin modifications followed by sequencing chromatin immunoprecipitation (cfChIP-seq) in blood samples. A blood sample of each patient will be collected for cfChIP-seq analysis in the baseline, before any dose of study treatment (week0)

  Time point: At baseline, before any dose of study treatment

• Gene expression of molecular biomarkers characteristics of the pathology

  Gene expression levels in the sample will be reported as media and interquartile range for each one of the biomarkers included in the determination. Determination of the expression of the molecular markers will perform applied chromatin immunoprecipitation of cell-free nucleosomes carrying active chromatin modifications followed by sequencing chromatin immunoprecipitation (cfChIP-seq) in blood samples. A blood sample of each patient will be collected and cfChIP-seq test will be performed as soon as the patient progresses according to RECIST 1.1 guidelines

  Time point: Throughout the study period, approximately 2 years per patient

Secondary Outcomes (7)

• Objective response rate (ORR)

  Throughout the study period, approximately 2 years per patient

• Disease control rate (DCR)

  Throughout the study period, approximately 2 years per patient

• Duration of response (DoR)

  Throughout the study period, approximately 2 years per patient

• Progression-free survival (PFS)

  Throughout the study period, approximately 2 years per patient

• Overall survival (OS)

  Throughout the study period, approximately 2 years per patient

Study Arms (1)

Cabozantinib, 60 mg

EXPERIMENTAL

Patients with advanced radioactive-iodine refractory DTC who progressed to previous TKIs (including but not limited to lenvatinib or sunitinib). Patients will have not received previously cabozantinib, selective small-molecule BRAF kinase inhibitors, immune checkpoint inhibitor therapy, or systemic chemotherapy regimens.

Drug: Cabozantinib

Interventions

Cabozantinib DRUG

* All enrolled patients will receive cabozantinib at a fixed dose of 60 mg once a day (QD). Patients will continue study treatment until PD (either clinical or radiological), or until unacceptable toxicity, the need for another systemic anticancer treatment, or other reasons for treatment discontinuation. * Patients will take the tablet(s) once daily at bed time except for Week 1 Day 1: the first dose of study treatment will be administered in the clinic so that each patient can be observed for initial tolerability. Subsequent doses will be self-administered at home. The tablets should be swallowed whole and not crushed and administered fasting for at least 2 hours before through 1 hour after. If a patient misses a dose, the missed dose should not be taken if it is less than 12 hours before the next dose.

Cabozantinib, 60 mg

Eligibility Criteria

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

You may qualify if:

• Male or female subjects ≥ 18 years old.
• Written informed consent approved by the Independent Ethics Committee (IEC), prior to the performance of any trial activities.
• Histologically or cytologically confirmed diagnosis of DTC, including the following subtypes:
• (Note: results of a previous biopsy will be accepted):
• Papillary thyroid carcinoma (PTC) including histological variants of PTC such as follicular variant, tall cell, columnar cell, cribriform-morular, solid, oxyphil, Warthin-like, trabecular, tumor with nodular fasciitis-like stroma, Hürthle cell variant of papillary carcinoma, poorly differentiated.
• Follicular thyroid carcinoma (FTC) including histological variants of FTC such as Hürthle cell, clear cell, insular, and poorly differentiated.
• Measurable disease according to RECIST 1.1 on computed tomography/magnetic resonance imaging (CT/MRI) performed within 28 days prior to first dose of study treatment.
• Must have been previously treated with or deemed ineligible for treatment with Iodine-131 for DTC.
• Must have been previously treated and experienced documented radiographic progression per RECIST 1.1 with one or two of the following vascular endothelial growth factor (VEGF) targeting TKI agents for DTC:
• Lenvatinib first-line or,
• Sorafenib first-line or,
• Two prior vascular endothelial growth factor receptor (VEGFR) TKIs.
• Recovery to baseline or ≤ Grade 1 (Common Terminology Criteria for Adverse Events Version 5 \[CTCAE v 5.0\]) from toxicities related to any prior treatments, unless AEs are clinically nonsignificant and/or stable on supportive therapy.
• Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.
• Adequate organ and bone marrow function based upon meeting all of the following laboratory criteria within 10 days before first dose of study treatment:

You may not qualify if:

• Prior treatment with any of the following:
• Cabozantinib.
• Selective small-molecule BRAF kinase inhibitor (eg, vemurafenib, dabrafenib).
• Immune checkpoint inhibitor therapy (eg, PD-1 or PD-L1 targeting agent).
• Systemic chemotherapy regimen (given as a single agent or in combination with another chemotherapy agent).
• Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks or 5 half-lives of the agent, whichever is longer, before first dose of study treatment.
• Receipt of any type of anticancer antibody (including investigational antibody) within 4 weeks before first dose of study treatment.
• Receipt of radiation therapy for bone metastasis within 2 weeks or any other radiation therapy within 4 weeks before first dose of study treatment. Patients with clinically relevant ongoing complications from prior radiation therapy that have not completely resolved are not eligible (eg, radiation esophagitis or other inflammation of the viscera).
• Concomitant anticoagulation with oral anticoagulants (eg, warfarin, direct thrombin and Factor Xa inhibitors) or platelet inhibitors (eg, clopidogrel), except for the following allowed anticoagulants:
• Low-dose aspirin for cardioprotection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).
• Anticoagulation with therapeutic doses of LMWH in subjects without known brain metastases who are on a stable dose of LMWH for at least 6 weeks before first dose of study treatment and who have had no clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.
• The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• a. Cardiovascular disorders: i. Congestive heart failure class 3 or 4 as defined by the New York Heart Association, unstable angina pectoris, serious cardiac arrhythmias.
• ii. Uncontrolled hypertension defined as sustained BP \> 150 mm Hg systolic or \> 100 mm Hg diastolic despite optimal antihypertensive treatment.
• iii. Stroke (including transient ischemic attack \[TIA\]), myocardial infarction, or other ischemic event, or thromboembolic event (eg, deep venous thrombosis \[DVT\], pulmonary embolism) within 6 months before first dose of study treatment. Note: Patients with a more recent diagnosis of DVT are allowed if stable, asymptomatic, and treated with LMWH for at least 6 weeks before first dose of study treatment.

Sponsors & Collaborators

• Grupo Espanol de Tumores Neuroendocrinos: lead
• Ipsen: collaborator
• MFAR: collaborator

Study Sites (9)

Complexo Hospitalario Universitario A Coruña

A Coruña, A Coruña, 15006, Spain

Location

Hospital Universitario Vall d'Hebron

Barcelona, Barcelona, 08035, Spain

Location

Hospital Clínic de Barcelona

Barcelona, Barcelona, 08036, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, Madrid, 28034, Spain

Location

Hospital Clínico San Carlos

Madrid, Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Madrid, 28041, Spain

Location

Hospital General Universitario Morales Meseguer

Murcia, Murcia, 30008, Spain

Location

Hospital Universitario Central de Asturias

Oviedo, Principality of Asturias, 33011, Spain

Location

Complejo Asistencial Universitario de Salamanca

Salamanca, Salamanca, 37007, Spain

Location

MeSH Terms

Conditions

Neoplasms; Thyroid Diseases

Interventions

cabozantinib

Condition Hierarchy (Ancestors)

Endocrine System Diseases

Study Officials

• Jaume Jaume Capdevila, M.D; PhD

  Hospital Vall d'Hebron

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Experimental arm Patients with advanced radioactive-iodine refractory DTC who progressed to previous TKIs (including but not limited to lenvatinib or sunitinib). Patients will have not received previously cabozantinib, selective small-molecule BRAF kinase inhibitors, immune checkpoint inhibitor therapy, or systemic chemotherapy regimens All patients will receive cabozantinib at a fixed dose of 60 mg once a day (QD). Patients will continue study treatment until PD (either clinical or radiological), or until unacceptable toxicity, the need for another systemic anticancer treatment, or other reasons for treatment discontinuation.

Study Record Dates

• First Submitted: December 2, 2022
• First Posted: December 21, 2022
• Study Start: May 25, 2023
• Primary Completion: November 30, 2025
• Study Completion: November 30, 2025
• Last Updated: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

ES (9)