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

Sponsor

Exelixis (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT01896479

Collaborator

(none)

250

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Medullary Thyroid Cancer	Drug: Cabozantinib (XL184) 140 mg Drug: Cabozantinib (XL184) 60 mg Drug: Placebo tablet Drug: Placebo capsule	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

250 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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 Start Date :

Dec 1, 2014

Actual Primary Completion Date :

Jul 1, 2020

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Progression Free Survival [Up to 31 months]
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.

Secondary Outcome Measures

Objective Response Rate [Up to 31 months]
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.

Other Outcome Measures

Safety and tolerability of cabozantinib as assessed by adverse events. [Up to 31 months]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

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

Contacts and Locations

Locations

	City	State	Country	Postal Code
1	St. Leonards	New South Wales	Australia	2065
2	Herston	Queensland	Australia	4006
3	Kurralta Park	South Australia	Australia	5037
4	Heidelberg	Victoria	Australia	3084
5	Parkville	Victoria	Australia	3050
6	Québec	Quebec	Canada	JIH 5N4
7	Toronto		Canada	M5G 2M9
8	Osijek		Croatia	31000
9	Zagreb		Croatia	10000
10	Zagreb		Croatia	1000
11	Bordeaux	Gironde	France	33076
12	Angers	Maine-et-Loire	France	49933
13	Lyon	Rhône	France	69373
14	Villejuif	Val-de-Marne	France	94805
15	Dijon		France	21079
16	Paris		France	75013
17	Strasbourg Cedex		France	67065
18	Budapest		Hungary	1088
19	Debrecen		Hungary	4032
20	Jerusalem		Israel	91120
21	Petach Tikva		Israel	49100
22	Safed		Israel	13100
23	Catania	CT	Italy	95124
24	Roma	RM	Italy	00161
25	Sienna	SI	Italy	53100
26	Pisa	Toscana	Italy	56124
27	Milano		Italy	20133
28	Padua		Italy	35138
29	Torino		Italy	10153
30	Goyang	Gyeonggido	Korea, Republic of	410769
31	Seoul		Korea, Republic of	110744
32	Seoul		Korea, Republic of	135-710
33	Amsterdam	Noord Holland	Netherlands	1066 CX
34	Leiden	Zuid-Holland	Netherlands	2333 ZA
35	Groningen		Netherlands	9713 GZ
36	Gliwice	Slaskie	Poland	44-100
37	Poznań	Wielkopolskie	Poland	60-355
38	Bucharest		Romania	10825
39	Bucharest		Romania	11863
40	Cluj-Napoca		Romania	400058
41	Timisoara		Romania	300723
42	Novosibirsk		Russian Federation	630068
43	Obninsk		Russian Federation	249036
44	St. Petersburg		Russian Federation	197089
45	Yaroslavl		Russian Federation	150040
46	Barcelona		Spain	08035
47	Madrid		Spain	28034
48	Madrid		Spain	28046
49	Lund	Skane Ian	Sweden	SE-22185
50	Uppsala	Uppsala Ian	Sweden	75185