Clinical trial NCT01896479: A Study of Two Different Doses of Cabozantinib (XL184) in Progressive, Metastatic Medullary Thyroid Cancer
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Medullary Thyroid Cancer
Keywords: thyroid cancer
medullary thyroid cancer
Lead sponsor: Exelixis
Sponsor class: INDUSTRY
First posted: 2013-07-11
Enrollment: 247
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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 outcomes:
measure: Progression Free Survival
timeFrame: Up to 31 months
Secondary outcomes:
measure: Objective Response Rate
timeFrame: Up to 31 months
Other outcomes:
measure: Safety and tolerability of cabozantinib as assessed by adverse events.
timeFrame: Up to 31 months
Locations:
city: St. Leonards
country: Australia
state: New South Wales
city: Herston
country: Australia
state: Queensland
city: Kurralta Park
country: Australia
state: South Australia
city: Parkville
country: Australia
state: Victoria
city: Québec
country: Canada
state: Quebec
city: Toronto
country: Canada
city: Osijek
country: Croatia
city: Zagreb
country: Croatia
city: Zagreb
country: Croatia
city: Bordeaux
country: France
state: Gironde
city: Angers
country: France
state: Maine-et-Loire
city: Lyon
country: France
state: Rhône
city: Villejuif
country: France
state: Val-de-Marne
city: Dijon
country: France
city: Paris
country: France
city: Strasbourg Cedex
country: France
city: Budapest
country: Hungary
city: Debrecen
country: Hungary
city: Jerusalem
country: Israel
city: Petach Tikva
country: Israel
city: Safed
country: Israel
city: Catania
country: Italy
state: CT
city: Roma
country: Italy
state: RM
city: Sienna
country: Italy
state: SI
city: Pisa
country: Italy
state: Toscana
city: Milano
country: Italy
city: Padua
country: Italy
city: Torino
country: Italy
city: Goyang
country: Korea, Republic of
state: Gyeonggido
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Amsterdam
country: Netherlands
state: Noord Holland
city: Leiden
country: Netherlands
state: Zuid-Holland
city: Groningen
country: Netherlands
city: Gliwice
country: Poland
state: Slaskie
city: Poznań
country: Poland
state: Wielkopolskie
city: Bucharest
country: Romania
city: Bucharest
country: Romania
city: Cluj-Napoca
country: Romania
city: Timisoara
country: Romania
city: Novosibirsk
country: Russian Federation
city: Obninsk
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Yaroslavl
country: Russian Federation
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Lund
country: Sweden
state: Skane Ian
city: Uppsala
country: Sweden
state: Uppsala Ian
Study officials:
References:
citation: 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.