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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Medullary Thyroid Cancer
• Intervention / Treatment: Drug: Cabozantinib (XL184) 140 mg; Drug: Placebo tablet; Drug: Cabozantinib (XL184) 60 mg; Drug: Placebo capsule

• Study Type: Interventional
• Enrollment (Actual): 247
• Phase: Phase 4

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • St. Leonards, New South Wales, Australia, 2065
  • Queensland
    • Herston, Queensland, Australia, 4006
  • South Australia
    • Kurralta Park, South Australia, Australia, 5037
  • Victoria
    • Parkville, Victoria, Australia, 3050
• Canada
  • Toronto, Canada, M5G 2M9
  • Quebec
    • Québec, Quebec, Canada, JIH 5N4
• Croatia
  • Osijek, Croatia, 31000
  • Zagreb, Croatia, 10000
  • Zagreb, Croatia, 1000
• France
  • Dijon, France, 21079
  • Paris, France, 75013
  • Strasbourg Cedex, France, 67065
  • Gironde
    • Bordeaux, Gironde, France, 33076
  • Maine-et-Loire
    • Angers, Maine-et-Loire, France, 49933
  • Rhône
    • Lyon, Rhône, France, 69373
  • Val-de-Marne
    • Villejuif, Val-de-Marne, France, 94805
• Hungary
  • Budapest, Hungary, 1088
  • Debrecen, Hungary, 4032
• Israel
  • Jerusalem, Israel, 91120
  • Petach Tikva, Israel, 49100
  • Safed, Israel, 13100
• Italy
  • Milano, Italy, 20133
  • Padua, Italy, 35138
  • Torino, Italy, 10153
  • CT
    • Catania, CT, Italy, 95124
  • RM
    • Roma, RM, Italy, 00161
  • SI
    • Sienna, SI, Italy, 53100
  • Toscana
    • Pisa, Toscana, Italy, 56124
• Korea, Republic of
  • Seoul, Korea, Republic of, 135-710
  • Seoul, Korea, Republic of, 110744
  • Gyeonggido
    • Goyang, Gyeonggido, Korea, Republic of, 410769
• Netherlands
  • Groningen, Netherlands, 9713 GZ
  • Noord Holland
    • Amsterdam, Noord Holland, Netherlands, 1066 CX
  • Zuid-Holland
    • Leiden, Zuid-Holland, Netherlands, 2333 ZA
• Poland
  • Slaskie
    • Gliwice, Slaskie, Poland, 44-100
  • Wielkopolskie
    • Poznań, Wielkopolskie, Poland, 60-355
• Romania
  • Bucharest, Romania, 10825
  • Bucharest, Romania, 11863
  • Cluj-Napoca, Romania, 400058
  • Timisoara, Romania, 300723
• Russian Federation
  • Novosibirsk, Russian Federation, 630068
  • Obninsk, Russian Federation, 249036
  • St. Petersburg, Russian Federation, 197089
  • Yaroslavl, Russian Federation, 150040
• Spain
  • Barcelona, Spain, 08035
  • Madrid, Spain, 28046
  • Madrid, Spain, 28034
• Sweden
  • Skane Ian
    • Lund, Skane Ian, Sweden, SE-22185
  • Uppsala Ian
    • Uppsala, Uppsala Ian, Sweden, 75185

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. The subject has a histologically confirmed diagnosis of MTC.
2. 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.
3. 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.
4. 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.
5. 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.
6. The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 at screening.
7. The subject has adequate organ and marrow function
8. The subject is capable of understanding and complying with the protocol requirements and has signed the informed consent document.
9. 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.

Exclusion Criteria:

1. The subject has previously received cabozantinib.
2. 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.
3. Receipt of any systemic anti-tumor therapy within 28 days of randomization (42 days for nitrosoureas or/ mitomycin C).
4. Receipt of any other type of investigational agent within 28 days of randomization.
5. 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.
6. 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.
7. Treatment at therapeutic doses with oral anticoagulants or platelet inhibitors (examples are warfarin and clopidogrel).
8. The subject has uncontrolled, significant intercurrent illness including, but not limited to, cardiovascular disorders, gastrointestinal disorders, active infections, non-healing wounds, recent surgery.
9. Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms within 28 days before randomization.
10. The subject is unable to swallow multiple tablets or capsules.
11. The subject has a previously identified allergy or hypersensitivity to components of the study treatment formulation.
12. The subject is pregnant or breastfeeding.
13. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cabozantinib (XL184) 140 mg; Cabozantinib (XL184) 140 mg as capsules and placebo tablets administered orally once a day.	Drug: Cabozantinib (XL184) 140 mg; Drug: Placebo tablet
Experimental: Cabozantinib (XL184) 60 mg; Cabozantinib (XL184) 60 mg as tablets and placebo capsules administered orally once a day.	Drug: Cabozantinib (XL184) 60 mg; Drug: Placebo capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	PFS is measured from randomization until the date of first documented disease progression or date of death from any cause, whichever comes first. Assessed for up to 31 months.	Up to 31 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	ORR is the proportion of subjects with measurable disease at baseline and who experience a best overall response of complete response (CR) or partial response (PR) which is confirmed ≥ 28 days later. Assessed for up to 31 months.	Up to 31 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of cabozantinib as assessed by adverse events.	Adverse events are measured from informed consent and at least through 30 days after the date of a decision to discontinue study treatment. Assessed for up to 31 months.	Up to 31 months

Collaborators and Investigators

• Sponsor: Exelixis

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (Actual): July 1, 2020
• Study Completion (Estimated): December 1, 2023

Study Registration Dates

• First Submitted: July 8, 2013
• First Submitted That Met QC Criteria: July 8, 2013
• First Posted (Estimated): July 11, 2013

Study Record Updates

• Last Update Posted (Actual): July 12, 2023
• Last Update Submitted That Met QC Criteria: July 7, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: thyroid cancer; medullary thyroid cancer
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Thyroid Diseases; Thyroid Neoplasms; Carcinoma, Neuroendocrine
• Other Study ID Numbers: XL184-401

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No