Medullary Thyroid CancerPhase 4EXAMINERNCT01896479
A Study of Two Different Doses of Cabozantinib (XL184) in Progressive, Metastatic Medullary Thyroid Cancer
A Phase 4 study testing Cabozantinib (XL184) 140 mg and Cabozantinib (XL184) 60 mg in people with Medullary Thyroid Cancer, run by Exelixis at 49 sites in 14 countries.
Trial summary
The objective of this study is to evaluate the efficacy and safety of oral cabozantinib at a 60 mg dose compared with a 140 mg dose in subjects with progressive, metastatic MTC. It will test if the lower dose results in similar progression free survival (PFS) and overall response rate (ORR) with fewer adverse events… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Medullary Thyroid Cancer
- What is being tested?
- Cabozantinib (XL184) 140 mg and Cabozantinib (XL184) 60 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 247 participants
- Where
- 49 sitesin 14 countries
- Study dates
- 25 Feb 2015to 31 Jan 2035
- Phase
- Phase 4
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
- The subject has a histologically confirmed diagnosis of MTC.
- All subjects will need to be tested for RET mutational status. If subjects do not have documentation confirming they have a RET mutation, a sample of their tumor (taken either during screening or from a procedure within 6 months prior to randomization) will need to be tested.
- The subject has measurable disease per RECIST 1.1 that is metastatic as determined by the investigator based upon computerized tomography (CT), magnetic resonance imaging (MRI), PET scan, bone scan, or X-ray taken within 28 days before randomization.
- The subject has documented worsening of disease (progressive disease) at screening as compared with a previous CT, PETor MRI scan, bone scan, or X-ray as determined by the investigator per RECIST 1.1 on qualifying screening images taken within 28 days prior to randomization as compared to previous images taken within 14 months before the qualifying screening images.
- The subject has recovered to baseline or CTCAE v4.0 (Common Terminology Criteria for Adverse Events, version 4.0) ≤ Grade 1 from toxicities related to any prior treatments, unless AE(s) are clinically non-significant and/or stable on supportive therapy.
- The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 at screening.
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- The subject has adequate organ and marrow function
- The subject is capable of understanding and complying with the protocol requirements and has signed the informed consent document.
- Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (eg, barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 4 months after the last dose of study treatment.
Who cannot join
- The subject has previously received cabozantinib.
- Receipt of any type of small molecule kinase inhibitor or hormonal therapy within 28 days or 5 half-lives of the compound or active metabolites, whichever is shorter, before randomization.
- Receipt of any systemic anti-tumor therapy within 28 days of randomization (42 days for nitrosoureas or/ mitomycin C).
- Receipt of any other type of investigational agent within 28 days of randomization.
- Receipt of radiation therapy within 28 days (14 days for radiation for bone metastases) of randomization or radionuclide treatment within 42 days of randomization. Subject is ineligible if there are any clinically relevant ongoing complications from prior radiation therapy.
- The subject has untreated and/or active (progressing or requiring anticonvulsants or corticosteroids for symptomatic control) central nervous system (CNS) metastasis. Must have completed radiation therapy ≥ 28 days prior to randomization and be stable without corticosteroids or anti-convulsant treatment for ≥ 10 days.
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- Treatment at therapeutic doses with oral anticoagulants or platelet inhibitors (examples are warfarin and clopidogrel).
- The subject has uncontrolled, significant intercurrent illness including, but not limited to, cardiovascular disorders, gastrointestinal disorders, active infections, non-healing wounds, recent surgery.
- Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms within 28 days before randomization.
- The subject is unable to swallow multiple tablets or capsules.
- The subject has a previously identified allergy or hypersensitivity to components of the study treatment formulation.
- The subject is pregnant or breastfeeding.
- The subject has had a diagnosis of another malignancy within 2 years before randomization, except for superficial skin cancers, or localized, low-grade tumors deemed cured and not treated with systemic therapy.
Trial locations and contacts
49 sites in 14 countries.
49 sites in 14 countries
France7 sites
Study site
Angers, Maine-et-Loire, 49933
Study site
Bordeaux, Gironde, 33076
Study site
Dijon, 21079
Study site
Lyon, Rhône, 69373
Study site
Paris, 75013
Study site
Strasbourg, 67065
Study site
Villejuif, Val-de-Marne, 94805
Italy7 sites
Study site
Catania, CT, 95124
Study site
Milan, 20133
Study site
Padua, 35138
Study site
Pisa, Tuscany, 56124
Study site
Roma, RM, 00161
Study site
Siena, SI, 53100
Study site
Torino, 10153
Australia4 sites
Study site
Herston, Queensland, 4006
Study site
Kurralta Park, South Australia, 5037
Study site
Parkville, Victoria, 3050
Study site
St Leonards, New South Wales, 2065
Romania4 sites
Study site
Bucharest, 10825
Study site
Bucharest, 11863
Study site
Cluj-Napoca, 400058
Study site
Timișoara, 300723
Russia4 sites
Study site
Novosibirsk, 630068
Study site
Obninsk, 249036
Study site
Saint Petersburg, 197089
Study site
Yaroslavl, 150040
Croatia3 sites
Study site
Osijek, 31000
Study site
Zagreb, 10000
Study site
Zagreb, 1000
Israel3 sites
Study site
Jerusalem, 91120
Study site
Petah Tikva, 49100
Study site
Safed, 13100
Netherlands3 sites
Study site
Amsterdam, North Holland, 1066 CX
Study site
Groningen, 9713 GZ
Study site
Leiden, South Holland, 2333 ZA
South Korea3 sites
Study site
Goyang, Gyeonggido, 410769
Study site
Seoul, 110744
Study site
Seoul, 135-710
Spain3 sites
Study site
Barcelona, 08035
Study site
Madrid, 28034
Study site
Madrid, 28046
Poland2 sites
Study site
Gliwice, Silesian Voivodeship, 44-100
Study site
Poznan, Greater Poland Voivodeship, 60-355
Sweden2 sites
Study site
Lund, Skane Ian, SE-22185
Study site
Uppsala, Uppsala Ian, 75185
About this study
Official title: A Randomized, Double-blind Study To Evaluate the Efficacy and Safety of Cabozantinib (XL184) at 60 mg/Day Compared to a 140 mg/Day in Progressive, Metastatic Medullary Thyroid Cancer Patients
The objective of this study is to evaluate the efficacy and safety of oral cabozantinib at a 60 mg dose compared with a 140 mg dose in subjects with progressive, metastatic MTC. It will test if the lower dose results in similar progression free survival (PFS) and overall response rate (ORR) with fewer adverse events compared to the PFS, ORR and adverse events found in previous clinical trials of 140 mg.
- Conditions
- Medullary Thyroid Cancer
- Being tested
- Cabozantinib (XL184) 140 mg, Cabozantinib (XL184) 60 mg, Placebo tablet, Placebo capsule
- Keywords
- thyroid cancer, medullary thyroid cancer
- Medical subject headings
- Carcinoma, Medullary, Thyroid Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cabozantinib (XL184) 140 mgDrug
Cabozantinib (XL184) 60 mgDrug
Placebo tabletDrug
Placebo capsuleDrug
| Study group | Role | What they receive |
|---|---|---|
| Cabozantinib (XL184) 60 mg | Experimental | Cabozantinib (XL184) 140 mg as capsules and placebo tablets administered orally once a day. Receives: Drug: Cabozantinib (XL184) 60 mg; Drug: Placebo capsule |
| Cabozantinib (XL184) 140 mg | Experimental | Cabozantinib (XL184) 140 mg as tablets and placebo capsules administered orally once a day. Receives: Drug: Cabozantinib (XL184) 140 mg; Drug: Placebo tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival (PFS) Per Blinded Independent Radiology Committee (BIRC) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
PFS per BIRC per RECIST 1.1 was measured from randomization until the date of first documented disease progression or date of death from any cause, whichever came first, and was assessed for up to 31 months. The prespecified primary analysis was triggered by the required number of at least 150 events occurring in the ITT population, The data cutoff date for this event-driven analysis in the ITT population was when a total of 155 events were reported. Median PFS was calculated using the Kaplan-Meier estimates.
Measured: Median time of follow-up (from the date of randomization of the first participant through primary data cut off [15 July 2020]) was 30.2 months
Secondary outcomes (1)
Objective Response Rate (ORR) Per BIRC Per RECIST 1.1
ORR per BIRC per RECIST 1.1 is the percentage of ITT participants who experienced a best overall response of complete response (CR) or partial response (PR), confirmed ≥ 28 days later, CR defined as disappearance of all non-target lesions. All lymph nodes must have been non-pathological in size (<10 mm short axis). PR defined as unequivocal progression of non-target lesions. Unequivocal progression was to trump target lesion status. It must have been representative of overall disease status change, not a single lesion increase.
Measured: Median time of follow-up (from the date of randomization of the first participant through primary data cut off [15 July 2020]) was 30.2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2013 (estimated)
- Study start25 Feb 2015
- Primary completion15 Jul 2020
- Study completion31 Jan 2035 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Medullary Thyroid CancerStudies of the same condition, open and under way.
- More trials run by ExelixisThe sponsor's other registered studies.
- 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
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 247 participants (actual)
Sponsor and investigators
- Lead sponsor
- Exelixis
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01896479
- Sponsor's protocol ID
- XL184-401
- Other IDs
- 2024-516480-90-00
- Acronym
- EXAMINER
- Status last verified
- Sep 2026
- First submitted
- 8 Jul 2013
- Last updated
- 20 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Capdevila J, Klochikhin A, Leboulleux S, Isaev P, Badiu C, Robinson B, Hughes BGM, Keam B, Parnis F, Elisei R, Gajate P, Gan HK, Kapiteijn E, Locati L, Mangeshkar M, Faoro L, Krajewska J, Jarzab B. A Randomized, Double-Blind Noninferiority Study to Evaluate the Efficacy of the Cabozantinib Tablet at 60 mg Per Day Compared with the Cabozantinib Capsule at 140 mg Per Day in Patients with Progressive, Metastatic Medullary Thyroid Cancer. Thyroid. 2022 May;32(5):515-524. doi: 10.1089/thy.2022.0027.
PubMed 35403447