A Study of Two Different Doses of Cabozantinib (XL184) in Progressive, Metastatic Medullary Thyroid Cancer

NCT01896479 | Active Not Recruiting Phase 4 Results DMC

• 2 other identifiers: XL184-4012024-516480-90-00
• Study Type: interventional
• Target: 247
• Locations: 14 countries
• Sites: 49

Brief 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 compared to the PFS, ORR and adverse events found in previous clinical trials of 140 mg.

Conditions

Medullary Thyroid Cancer

Keywords

thyroid cancer; medullary thyroid cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  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

Study Arms (2)

Cabozantinib (XL184) 60 mg

EXPERIMENTAL

Cabozantinib (XL184) 140 mg as capsules and placebo tablets administered orally once a day.

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.

Drug: Cabozantinib (XL184) 140 mg; Drug: Placebo tablet

Interventions

Cabozantinib (XL184) 140 mg DRUG

Cabozantinib (XL184) 140 mg

Cabozantinib (XL184) 60 mg DRUG

Cabozantinib (XL184) 60 mg

Placebo tablet DRUG

Cabozantinib (XL184) 140 mg

Placebo capsule DRUG

Cabozantinib (XL184) 60 mg

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Exelixis: lead

Study Sites (49)

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St Leonards, New South Wales, 2065, Australia

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Herston, Queensland, 4006, Australia

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Kurralta Park, South Australia, 5037, Australia

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Parkville, Victoria, 3050, Australia

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Québec, Quebec, JIH 5N4, Canada

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Toronto, M5G 2M9, Canada

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Osijek, 31000, Croatia

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Zagreb, 10000, Croatia

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Zagreb, 1000, Croatia

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Bordeaux, Gironde, 33076, France

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Angers, Maine-et-Loire, 49933, France

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Lyon, Rhône, 69373, France

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Villejuif, Val-de-Marne, 94805, France

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Dijon, 21079, France

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Paris, 75013, France

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Strasbourg, 67065, France

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Budapest, 1088, Hungary

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Debrecen, 4032, Hungary

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Jerusalem, 91120, Israel

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Petah Tikva, 49100, Israel

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Safed, 13100, Israel

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Catania, CT, 95124, Italy

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Roma, RM, 00161, Italy

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Siena, SI, 53100, Italy

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Pisa, Tuscany, 56124, Italy

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Milan, 20133, Italy

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Padua, 35138, Italy

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Torino, 10153, Italy

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Amsterdam, North Holland, 1066 CX, Netherlands

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Leiden, South Holland, 2333 ZA, Netherlands

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Groningen, 9713 GZ, Netherlands

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Poznan, Greater Poland Voivodeship, 60-355, Poland

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Gliwice, Silesian Voivodeship, 44-100, Poland

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Bucharest, 10825, Romania

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Bucharest, 11863, Romania

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Cluj-Napoca, 400058, Romania

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Timișoara, 300723, Romania

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Novosibirsk, 630068, Russia

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Obninsk, 249036, Russia

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Saint Petersburg, 197089, Russia

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Yaroslavl, 150040, Russia

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Goyang, Gyeonggido, 410769, South Korea

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Seoul, 110744, South Korea

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Seoul, 135-710, South Korea

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Barcelona, 08035, Spain

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Madrid, 28034, Spain

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Madrid, 28046, Spain

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Lund, Skane Ian, SE-22185, Sweden

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Uppsala, Uppsala Ian, 75185, Sweden

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Related Publications (1)

• 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.

  PMID: 35403447 DERIVED

MeSH Terms

Conditions

Carcinoma, Medullary; Thyroid Neoplasms

Interventions

cabozantinib

Condition Hierarchy (Ancestors)

Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Ductal, Lobular, and Medullary; Neoplasms, Nerve Tissue; Endocrine Gland Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases

Results Point of Contact

• Title: Exelixis Medical Information
• Organization: Exelixis, Inc.

druginfo@exelixis.com

855-292-3935

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2013
• First Posted: July 11, 2013
• Study Start: February 25, 2015
• Primary Completion: July 15, 2020
• Study Completion (Estimated): January 1, 2035
• Last Updated: September 2, 2025
• Results First Posted: September 2, 2025

Record last verified: 2025-08

Locations

KR (3); ES (3); SE (2); NL (3); IT (7); FR (7); HU (2); IL (3); CR (3); RU (4); CA (2); RO (4); PL (2); AU (4)