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

Primary Purpose

Medullary Thyroid Cancer

Status
Active
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Cabozantinib (XL184) 140 mg
Cabozantinib (XL184) 60 mg
Placebo tablet
Placebo capsule
Sponsored by
Exelixis
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Medullary Thyroid Cancer focused on measuring thyroid cancer, medullary thyroid cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Cabozantinib (XL184) 140 mg

Cabozantinib (XL184) 60 mg

Arm Description

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

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

Outcomes

Primary Outcome Measures

Progression Free Survival
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
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.

Full Information

First Posted
July 8, 2013
Last Updated
July 7, 2023
Sponsor
Exelixis
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1. Study Identification

Unique Protocol Identification Number
NCT01896479
Brief Title
A Study of Two Different Doses of Cabozantinib (XL184) in Progressive, Metastatic Medullary Thyroid Cancer
Acronym
EXAMINER
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

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 2014 (undefined)
Primary Completion Date
July 2020 (Actual)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Exelixis

4. Oversight

Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Medullary Thyroid Cancer
Keywords
thyroid cancer, medullary thyroid cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
247 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cabozantinib (XL184) 140 mg
Arm Type
Experimental
Arm Description
Cabozantinib (XL184) 140 mg as capsules and placebo tablets administered orally once a day.
Arm Title
Cabozantinib (XL184) 60 mg
Arm Type
Experimental
Arm Description
Cabozantinib (XL184) 60 mg as tablets and placebo capsules administered orally once a day.
Intervention Type
Drug
Intervention Name(s)
Cabozantinib (XL184) 140 mg
Intervention Type
Drug
Intervention Name(s)
Cabozantinib (XL184) 60 mg
Intervention Type
Drug
Intervention Name(s)
Placebo tablet
Intervention Type
Drug
Intervention Name(s)
Placebo capsule
Primary Outcome Measure Information:
Title
Progression Free Survival
Description
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.
Time Frame
Up to 31 months
Secondary Outcome Measure Information:
Title
Objective Response Rate
Description
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.
Time Frame
Up to 31 months
Other Pre-specified Outcome Measures:
Title
Safety and tolerability of cabozantinib as assessed by adverse events.
Description
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.
Time Frame
Up to 31 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
City
St. Leonards
State/Province
New South Wales
ZIP/Postal Code
2065
Country
Australia
City
Herston
State/Province
Queensland
ZIP/Postal Code
4006
Country
Australia
City
Kurralta Park
State/Province
South Australia
ZIP/Postal Code
5037
Country
Australia
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3050
Country
Australia
City
Québec
State/Province
Quebec
ZIP/Postal Code
JIH 5N4
Country
Canada
City
Toronto
ZIP/Postal Code
M5G 2M9
Country
Canada
City
Osijek
ZIP/Postal Code
31000
Country
Croatia
City
Zagreb
ZIP/Postal Code
10000
Country
Croatia
City
Zagreb
ZIP/Postal Code
1000
Country
Croatia
City
Bordeaux
State/Province
Gironde
ZIP/Postal Code
33076
Country
France
City
Angers
State/Province
Maine-et-Loire
ZIP/Postal Code
49933
Country
France
City
Lyon
State/Province
Rhône
ZIP/Postal Code
69373
Country
France
City
Villejuif
State/Province
Val-de-Marne
ZIP/Postal Code
94805
Country
France
City
Dijon
ZIP/Postal Code
21079
Country
France
City
Paris
ZIP/Postal Code
75013
Country
France
City
Strasbourg Cedex
ZIP/Postal Code
67065
Country
France
City
Budapest
ZIP/Postal Code
1088
Country
Hungary
City
Debrecen
ZIP/Postal Code
4032
Country
Hungary
City
Jerusalem
ZIP/Postal Code
91120
Country
Israel
City
Petach Tikva
ZIP/Postal Code
49100
Country
Israel
City
Safed
ZIP/Postal Code
13100
Country
Israel
City
Catania
State/Province
CT
ZIP/Postal Code
95124
Country
Italy
City
Roma
State/Province
RM
ZIP/Postal Code
00161
Country
Italy
City
Sienna
State/Province
SI
ZIP/Postal Code
53100
Country
Italy
City
Pisa
State/Province
Toscana
ZIP/Postal Code
56124
Country
Italy
City
Milano
ZIP/Postal Code
20133
Country
Italy
City
Padua
ZIP/Postal Code
35138
Country
Italy
City
Torino
ZIP/Postal Code
10153
Country
Italy
City
Goyang
State/Province
Gyeonggido
ZIP/Postal Code
410769
Country
Korea, Republic of
City
Seoul
ZIP/Postal Code
110744
Country
Korea, Republic of
City
Seoul
ZIP/Postal Code
135-710
Country
Korea, Republic of
City
Amsterdam
State/Province
Noord Holland
ZIP/Postal Code
1066 CX
Country
Netherlands
City
Leiden
State/Province
Zuid-Holland
ZIP/Postal Code
2333 ZA
Country
Netherlands
City
Groningen
ZIP/Postal Code
9713 GZ
Country
Netherlands
City
Gliwice
State/Province
Slaskie
ZIP/Postal Code
44-100
Country
Poland
City
Poznań
State/Province
Wielkopolskie
ZIP/Postal Code
60-355
Country
Poland
City
Bucharest
ZIP/Postal Code
10825
Country
Romania
City
Bucharest
ZIP/Postal Code
11863
Country
Romania
City
Cluj-Napoca
ZIP/Postal Code
400058
Country
Romania
City
Timisoara
ZIP/Postal Code
300723
Country
Romania
City
Novosibirsk
ZIP/Postal Code
630068
Country
Russian Federation
City
Obninsk
ZIP/Postal Code
249036
Country
Russian Federation
City
St. Petersburg
ZIP/Postal Code
197089
Country
Russian Federation
City
Yaroslavl
ZIP/Postal Code
150040
Country
Russian Federation
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
City
Madrid
ZIP/Postal Code
28034
Country
Spain
City
Madrid
ZIP/Postal Code
28046
Country
Spain
City
Lund
State/Province
Skane Ian
ZIP/Postal Code
SE-22185
Country
Sweden
City
Uppsala
State/Province
Uppsala Ian
ZIP/Postal Code
75185
Country
Sweden

12. IPD Sharing Statement

Citations:
PubMed Identifier
35403447
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.
Results Reference
derived

Learn more about this trial

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

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