AzTrials
AzTrials

Differentiated Thyroid CancerPhase 2CABOTHYROIDNCT05660954

Cabozantinib In Advanced Radioactive-Iodine Refractory Differentiated Thyroid Cancer.

A Phase 2 study testing Cabozantinib in people with Differentiated Thyroid Cancer, run by Grupo Espanol de Tumores Neuroendocrinos at 9 sites in Spain.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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 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?
Cabozantinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
41 participants
Where
9 sitesSpain
Study dates
25 May 2023to 30 Nov 2025
Phase
Phase 2
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

  • 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.
Show all 36Show fewer
  • 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:
  • Absolute neutrophil count ≥ 1500/mm3 (≥ 1.5 GI/L) without receipt of granulocyte colony-stimulating factor support within 2 weeks before screening laboratory sample collection.
  • Platelets ≥ 100,000/mm3 (≥ 100 GI/L) without receipt of transfusion within 2 weeks before screening laboratory sample collection
  • Hemoglobin ≥ 9 g/dL (≥ 90 g/L) without receipt of transfusion within 2 weeks before screening laboratory sample collection
  • Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) ≤ 3 × upper limit of normal (ULN). ALP ≤ 5 × ULN if the subject has documented bone metastases
  • Bilirubin ≤ 1.5 × the upper limit of normal (ULN). For subjects with known Gilbert's disease ≤ 3 × ULN
  • Serum creatinine ≤ 2.0 × ULN or calculated creatinine clearance ≥ 30 mL/min (≥ 0.5 mL/sec) using the Cockcroft-Gault
  • Urine protein/creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol)
  • Female subjects of childbearing potential (WOCBP) must provide a negative urine pregnancy test at screening, and must agree to use a medically accepted and highly effective birth control method (i.e. those with a failure rate less than 1%; for the duration of the study treatment and for 4 months after the final dose of cabozantinib.
  • A woman is considered of childbearing potential ( i.e. fertile) following menarche and until becoming post-menopausal unless permanently sterile. Women will be considered post-menopausal if they have been amenorrhoeic for 12 months without an alternative medical cause. The following age-specific requirements apply:
  • Amenorrheic for ≥1 year in the absence of chemotherapy and/or hormonal treatments
  • Luteinizing hormone (LH) and/or follicle stimulating hormone and/or estradiol levels in the post-menopausal range
  • Radiation induced oophorectomy with last menses >1 year ago
  • Chemotherapy induced menopause with >1 year interval since last menses
  • Surgical sterilization (bilateral oophorectomy or hysterectomy)
  • Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy)
  • Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
  • Non-sterile males must be willing to use a highly effective method of birth control for the duration of the study treatment and for 4 months after the final dose of cabozantinib.
  • A sterile male is defined as:
  • One for whom azoospermia has been previously demonstrated in a semen sample examination as definitive evidence of infertility.
  • Males with known "low sperm counts" (consistent with "sub-fertility") are not to be considered sterile for purposes of this study.
  • Capable of understanding and complying with the protocol requirements and signed informed consent.

Who cannot join

  • 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.
Show all 29Show fewer
  • 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).
  • Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study treatment. Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of inclusion.
  • 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:
  • Cardiovascular disorders: i. Congestive heart failure class 3 or 4 as defined by the New York Heart Association, unstable angina pectoris, serious cardiac arrhythmias.
  • Uncontrolled hypertension defined as sustained BP > 150 mm Hg systolic or > 100 mm Hg diastolic despite optimal antihypertensive treatment.
  • 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.
  • Gastrointestinal disorders (eg, malabsorption syndrome or gastric outlet obstruction) including those associated with a high risk of perforation or fistula formulation: i. Tumors invading the GI tract, active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis or acute obstruction of the pancreatic or biliary duct, or gastric outlet obstruction.
  • Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose of study treatment. Note: Complete healing of an intra-abdominal abscess must be confirmed prior to the first dose of study treatment.
  • Clinically significant hematemesis or hemoptysis of > 0.5 teaspoon (> 2.5 mL) of red blood or history of other significant bleeding within 3 months before the first dose of study treatment.
  • Cavitating pulmonary lesion(s) or known endobronchial disease manifestation. e. Lesions invading major pulmonary blood vessels. f. Other clinically significant disorders such as: i. Active infection requiring systemic treatment, infection with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome-related illness, or chronic hepatitis B (HBV) or C (HCV) infection.
  • Serious non-healing wound/ulcer/bone fracture. iii. Malabsorption syndrome. iv. Moderate to severe hepatic impairment (Child-Pugh B or C). v. Requirement for hemodialysis or peritoneal dialysis. vi. Uncontrolled diabetes mellitus. vii. History of solid organ transplantation.
  • Major surgery (eg, GI surgery, removal or biopsy of brain metastasis) within 8 weeks before the first dose of study treatment. Complete wound healing from major surgery must have occurred 4 weeks before the first dose of study treatment and from minor surgery (eg, simple excision, tooth extraction) at least 10 days before the first dose of study treatment. Patients with clinically relevant ongoing complications from prior surgery are not eligible.
  • Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms within 28 days before the first dose of study treatment.
  • Note: If a single ECG shows a QTcF with an absolute value > 500 ms, two additional ECGs at intervals of approximately 3 min must be performed within 30 min after the initial ECG, and the average of these 3 consecutive results for QTcF will be used to determine eligibility.
  • Patients who are not able to swallow tablets.
  • Previously identified allergy or hypersensitivity to components of the study treatment formulations.
  • Diagnosis of another malignancy within 3 years before the first dose of study treatment, except for superficial skin cancers, or localized, low grade tumors deemed cured and not treated with systemic therapy.
  • Women pregnant or breastfeeding. Fertile and sexually active patients who are not willing to use the appropriate highly effective contraceptive methods.
  • Any underlying medical or psychiatric disorder, which, in the opinion of the investigator, makes the administration of cabozantinib unsafe or interferes with the informed consent process or trial procedures.

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

Spain9 sites

  • Complexo Hospitalario Universitario A Coruña

    A Coruña, A Coruña, 15006

  • Hospital Universitario Vall d'Hebron

    Barcelona, Barcelona, 08035

  • Hospital Clínic de Barcelona

    Barcelona, Barcelona, 08036

  • Hospital Universitario Ramón y Cajal

    Madrid, Madrid, 28034

  • Hospital Clínico San Carlos

    Madrid, Madrid, 28040

  • Hospital Universitario 12 de Octubre

    Madrid, Madrid, 28041

  • Hospital General Universitario Morales Meseguer

    Murcia, Murcia, 30008

  • Hospital Universitario Central de Asturias

    Oviedo, Principality of Asturias, 33011

  • Complejo Asistencial Universitario de Salamanca

    Salamanca, Salamanca, 37007

Other trials in Spain

About this study

Official title: Biomarker Phase II Study Of Cabozantinib In Advanced Radioactive-Iodine Refractory Differentiated Thyroid Cancer.

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

Read the detailed description

The trial will enroll competitively up to 41 subjects; male and female, ≥ 18 years, with ECOG PS 0-1 patients with advanced radioactive-iodine refractory differentiated thyroid cancer (DTC) who progressed to previous Tyrosine kinase inhibitors (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.

The design includes a screening phase in which patient eligibility is addressed, a treatment phase, and a follow-up phase.

Study treatment will begin as soon as possible after signing the informed consent and inclusion will be completed.

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.

All patients will undergo periodic tumor assessments by CT or MRI scan every 12 weeks ± 14 days (3 months), and blood monitoring of tumor markers (i.e. thyroglobulin if applicable) every 12 weeks ± 3 days (2 months) from the start of study treatment until progression or patient withdrawal. Further CT/MRI scans could be performed upon suspicion of disease progression according to standard clinical practice and physician criteria. Safety will be assessed at every visit through continuous monitoring of signs and symptoms and periodic laboratory analysis.

The study includes the collection of two blood samples (baseline and after PD; 40 mL at each timepoint) for the determination of cf CHIP-seq (Chromatin immunoprecipitation-sequencing) and patient reported outcomes.

Being tested
Cabozantinib
Keywords
Cancer, Thyroid, Cabozantinib
Medical subject headings
Neoplasms, Thyroid Diseases

What participants receive

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

  • CabozantinibDrug

    • 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.
Study groups in NCT05660954
Study groupRoleWhat they receive
Cabozantinib, 60 mgExperimentalPatients 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.
Receives: Drug: Cabozantinib

What is being measured

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

  1. 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)

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

  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 and cfChIP-seq test will be performed as soon as the patient progresses according to RECIST 1.1 guidelines

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

Secondary outcomes (7)

  1. Objective response rate (ORR)

    Objective response rate (ORR), primary endpoint for efficacy: Assessed by the investigator through imaging follow-up (CT scan/MRI) using RECIST 1.1. This will be considered as the percentage/proportion of patients with confirmed complete response (CR) or partial response (PR) as their overall best response throughout the study period. Objective responses will be assessed locally by the investigator according to RECIST, version 1.1, and indicating the change in size of tumors as compared with baseline, at the first dose of study treatment.

    Measured: Throughout the study period, approximately 2 years per patient

  2. Disease control rate (DCR)

    Percentage/proportion of patients with complete response (CR) or partial response (PR), according to ORR definition for the trial, or maintained stable disease (SD) as their overall best response, assessed by imaging follow-up (CT scan/MRI) and RECIST 1.1 criteria. Stable disease should be maintained for at least 4 months to be considered as a Chemical, Biological, or Radiological (CBR) event

    Measured: Throughout the study period, approximately 2 years per patient

  3. Duration of response (DoR)

    DoR is defined as the time from first confirmed response (CR or PR), according to ORR definition for the trial, to the date of the documented PD as determined using RECIST 1.1 criteria or death due to any cause, whichever occurs first. Those patients with response and without PD or death event will be censored on the date of their last tumor assessment.

    Measured: Throughout the study period, approximately 2 years per patient

  4. Progression-free survival (PFS)

    PFS is defined as time from first dosing date to the date of confirmed PD according to RECIST 1.1. Patients alive and free of events at the date of the analysis will be censored at their last known tumor assessment. Patients who start a new treatment line without progression will be censored on the date of first dose of the subsequent anticancer treatment.

    Measured: Throughout the study period, approximately 2 years per patient

  5. Overall survival (OS)

    Defined as the time elapsed from the first dose of study treatment until death from any cause. We will assess the median OS, estimated by Kaplan-Meier. Patients alive and free of events at the date of the analysis will be censored at their last known contact. Survival will be assessed by recording patient status at each visit according to Table 1. Long term follow up to be performed at least every 6 months.

    Measured: Throughout the study period, approximately 2 years per patient

  6. Frequency of Adverse events (AEs) leading to treatment discontinuation.

    Percentage of patients experiencing an adverse event leading to discontinuation of treatment

    Measured: Throughout the study period, approximately 2 years per patient

  7. Health-related quality of life (HRQoL), assessed through the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) version 3.

    The EORTC QLQ-C30 questionnaire is a specific questionnaire validated for cancer that is composed of 30 questions or items. The questionnaire is structured in 5 functional scales (physical functioning, daily activities, emotional functioning, cognitive functioning and social functioning), 3 symptom scales (fatigue, pain and nausea, vomiting), 1 global health status scale, and 6 independent items (dyspnea, insomnia, anorexia, constipation, diarrhea and economic impact). Values between 1 and 4 (1: not at all, 2: a little, 3: quite, 4: a lot) are assigned according to the patient's responses to the item, only in items 29 and 30 are they evaluated with a score of 1 to 7 (1: dreadful, 7: excellent). The scores obtained are standardized and a score between 0 and 100 is obtained, which determines the level of impact of the cancer on the patient on each of the scales. A higher score indicating a better HRQoL.

    Measured: Throughout the study period, approximately 2 years per patient

Timeline

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

  1. First posted21 Dec 2022
  2. Study start25 May 2023
  3. Primary completion30 Nov 2025
  4. Study completion30 Nov 2025

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
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.
Masking
None (open label)
Enrolment
41 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05660954
Sponsor's protocol ID
GETNE-T2216
Acronym
CABOTHYROID
Status last verified
Apr 2026
First submitted
2 Dec 2022
Last updated
4 May 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: The individual participant data (IPD) anonymized could be shared upon request if the use is within the scope and protection level authorized by the patients by the signature of the informed consent

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cabozantinib in people with Differentiated Thyroid Cancer, run by Grupo Espanol de Tumores Neuroendocrinos at 9 sites in Spain.

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 36 inclusion and 29 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: finished, as of the sponsor's last update on 4 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in Spain. 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?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Gene expression of molecular biomarkers characteristics of the pathology (time frame: Time point: At baseline, before any dose of study treatment). The study lists 2 primary outcomes in all. 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 NCT05660954.

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 4 May 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in