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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01896479




Registration number
NCT01896479
Ethics application status
Date submitted
8/07/2013
Date registered
11/07/2013
Date last updated
12/07/2023

Titles & IDs
Public title
A Study of Two Different Doses of Cabozantinib (XL184) in Progressive, Metastatic Medullary Thyroid Cancer
Scientific 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
Secondary ID [1] 0 0
XL184-401
Universal Trial Number (UTN)
Trial acronym
EXAMINER
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Medullary Thyroid Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Thyroid
Cancer 0 0 0 0
Neuroendocrine tumour (NET)
Metabolic and Endocrine 0 0 0 0
Other endocrine disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cabozantinib (XL184) 140 mg
Treatment: Drugs - Cabozantinib (XL184) 60 mg
Treatment: Drugs - Placebo tablet
Treatment: Drugs - Placebo capsule

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

Experimental: Cabozantinib (XL184) 60 mg - Cabozantinib (XL184) 60 mg as tablets and placebo capsules administered orally once a day.


Treatment: Drugs: Cabozantinib (XL184) 140 mg


Treatment: Drugs: Cabozantinib (XL184) 60 mg


Treatment: Drugs: Placebo tablet


Treatment: Drugs: Placebo capsule
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression Free Survival
Timepoint [1] 0 0
Up to 31 months
Secondary outcome [1] 0 0
Objective Response Rate
Timepoint [1] 0 0
Up to 31 months

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/12/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2023
Actual
Sample size
Target
Accrual to date
Final
247
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
- St. Leonards
Recruitment hospital [2] 0 0
- Herston
Recruitment hospital [3] 0 0
- Kurralta Park
Recruitment hospital [4] 0 0
- Parkville
Recruitment postcode(s) [1] 0 0
2065 - St. Leonards
Recruitment postcode(s) [2] 0 0
4006 - Herston
Recruitment postcode(s) [3] 0 0
5037 - Kurralta Park
Recruitment postcode(s) [4] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
Canada
State/province [1] 0 0
Quebec
Country [2] 0 0
Canada
State/province [2] 0 0
Toronto
Country [3] 0 0
Croatia
State/province [3] 0 0
Osijek
Country [4] 0 0
Croatia
State/province [4] 0 0
Zagreb
Country [5] 0 0
France
State/province [5] 0 0
Gironde
Country [6] 0 0
France
State/province [6] 0 0
Maine-et-Loire
Country [7] 0 0
France
State/province [7] 0 0
Rhône
Country [8] 0 0
France
State/province [8] 0 0
Val-de-Marne
Country [9] 0 0
France
State/province [9] 0 0
Dijon
Country [10] 0 0
France
State/province [10] 0 0
Paris
Country [11] 0 0
France
State/province [11] 0 0
Strasbourg Cedex
Country [12] 0 0
Hungary
State/province [12] 0 0
Budapest
Country [13] 0 0
Hungary
State/province [13] 0 0
Debrecen
Country [14] 0 0
Israel
State/province [14] 0 0
Jerusalem
Country [15] 0 0
Israel
State/province [15] 0 0
Petach Tikva
Country [16] 0 0
Israel
State/province [16] 0 0
Safed
Country [17] 0 0
Italy
State/province [17] 0 0
CT
Country [18] 0 0
Italy
State/province [18] 0 0
RM
Country [19] 0 0
Italy
State/province [19] 0 0
SI
Country [20] 0 0
Italy
State/province [20] 0 0
Toscana
Country [21] 0 0
Italy
State/province [21] 0 0
Milano
Country [22] 0 0
Italy
State/province [22] 0 0
Padua
Country [23] 0 0
Italy
State/province [23] 0 0
Torino
Country [24] 0 0
Korea, Republic of
State/province [24] 0 0
Gyeonggido
Country [25] 0 0
Korea, Republic of
State/province [25] 0 0
Seoul
Country [26] 0 0
Netherlands
State/province [26] 0 0
Noord Holland
Country [27] 0 0
Netherlands
State/province [27] 0 0
Zuid-Holland
Country [28] 0 0
Netherlands
State/province [28] 0 0
Groningen
Country [29] 0 0
Poland
State/province [29] 0 0
Slaskie
Country [30] 0 0
Poland
State/province [30] 0 0
Wielkopolskie
Country [31] 0 0
Romania
State/province [31] 0 0
Bucharest
Country [32] 0 0
Romania
State/province [32] 0 0
Cluj-Napoca
Country [33] 0 0
Romania
State/province [33] 0 0
Timisoara
Country [34] 0 0
Russian Federation
State/province [34] 0 0
Novosibirsk
Country [35] 0 0
Russian Federation
State/province [35] 0 0
Obninsk
Country [36] 0 0
Russian Federation
State/province [36] 0 0
St. Petersburg
Country [37] 0 0
Russian Federation
State/province [37] 0 0
Yaroslavl
Country [38] 0 0
Spain
State/province [38] 0 0
Barcelona
Country [39] 0 0
Spain
State/province [39] 0 0
Madrid
Country [40] 0 0
Sweden
State/province [40] 0 0
Skane Ian
Country [41] 0 0
Sweden
State/province [41] 0 0
Uppsala Ian

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Exelixis
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01896479
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01896479