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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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.
Primary outcome measure(s)
Progression Free Survival (PFS) Per Blinded Independent Radiology Committee (BIRC) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (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 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.
Trial sites (49)
Facility
City
Region
Status
—
St Leonards
New South Wales
—
Herston
Queensland
—
Kurralta Park
South Australia
—
Parkville
Victoria
—
Québec
Quebec
—
Toronto
Canada
—
Osijek
Croatia
—
Zagreb
Croatia
—
Zagreb
Croatia
—
Bordeaux
Gironde
—
Angers
Maine-et-Loire
—
Lyon
Rhône
—
Villejuif
Val-de-Marne
—
Dijon
France
—
Paris
France
—
Strasbourg
France
—
Budapest
Hungary
—
Debrecen
Hungary
—
Jerusalem
Israel
—
Petah Tikva
Israel
—
Safed
Israel
—
Catania
CT
—
Roma
RM
—
Siena
SI
—
Pisa
Tuscany
—
Milan
Italy
—
Padua
Italy
—
Torino
Italy
—
Amsterdam
North Holland
—
Leiden
South Holland
—
Groningen
Netherlands
—
Poznan
Greater Poland Voivodeship
—
Gliwice
Silesian Voivodeship
—
Bucharest
Romania
—
Bucharest
Romania
—
Cluj-Napoca
Romania
—
Timișoara
Romania
—
Novosibirsk
Russia
—
Obninsk
Russia
—
Saint Petersburg
Russia
+ 9 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
We use cookies to analyse site traffic and improve your experience. With your consent, we may also use cookies for advertising. You can change your choice at any time.