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.
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
6. The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1
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.
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,
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.