Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04211337




Registration number
NCT04211337
Ethics application status
Date submitted
24/12/2019
Date registered
26/12/2019
Date last updated
18/01/2024

Titles & IDs
Public title
A Study of Selpercatinib (LY3527723) in Participants With RET-Mutant Medullary Thyroid Cancer
Scientific title
A Multicenter, Randomized, Open-label, Phase 3 Trial Comparing Selpercatinib to Physicians Choice of Cabozantinib or Vandetanib in Patients With Progressive, Advanced, Kinase Inhibitor Naïve, RET-Mutant Medullary Thyroid Cancer (LIBRETTO-531)
Secondary ID [1] 0 0
J2G-MC-JZJB
Secondary ID [2] 0 0
17478
Universal Trial Number (UTN)
Trial acronym
LIBRETTO-531
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(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - Selpercatinib
Treatment: Drugs - Cabozantinib
Treatment: Drugs - Vandetanib

Experimental: Selpercatinib - Selpercatinib given orally.

Active Comparator: Cabozantinib or Vandetanib - Cabozantinib or vandetanib given orally.


Treatment: Drugs: Selpercatinib
Administered orally

Treatment: Drugs: Cabozantinib
Administered orally

Treatment: Drugs: Vandetanib
Administered orally
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression Free Survival (PFS) by BICR
Timepoint [1] 0 0
Baseline to Progressive Disease or Death from Any Cause (Estimated at up to 30 Months)
Secondary outcome [1] 0 0
Treatment Failure-Free Survival (TFFS) by Blinded Independent Committee Review (BICR)
Timepoint [1] 0 0
Baseline to Progressive Disease, Unacceptable Toxicity or Death from Any Cause (Estimated at up to 30 Months)
Secondary outcome [2] 0 0
Overall Response Rate (ORR): Percentage of Participants with Complete Response (CR) or Partial Response (PR) by BICR
Timepoint [2] 0 0
Baseline through Disease Progression or Death (Estimated at up to 30 Months)
Secondary outcome [3] 0 0
Duration of Response (DoR) by BICR
Timepoint [3] 0 0
Date of CR or PR to Date of Disease Progression or Death Due to Any Cause (Estimated at up to 30 Months)
Secondary outcome [4] 0 0
Overall Survival (OS)
Timepoint [4] 0 0
Baseline to Date of Death from Any Cause (Estimated at up to 60 Months)
Secondary outcome [5] 0 0
PFS2 by Investigator
Timepoint [5] 0 0
Baseline to Second Disease Progression or Death from Any Cause (Estimated at up to 48 Months)
Secondary outcome [6] 0 0
Comparative Tolerability: Percentage of Time with High Side Effect Bother Based on the Functional Assessment of Cancer Therapy-Side Effects (FACT-GP5)
Timepoint [6] 0 0
Baseline to Progressive Disease, Unacceptable Toxicity or Death from Any Cause (30 months)
Secondary outcome [7] 0 0
The Concordance of the Local Lab and the Central Lab RET Results: Percentage of Participants with RET-Positive Specimens as Called by the Central Lab, which is also RET-Positive as Called by a Local Lab (Positive Percent Agreement)
Timepoint [7] 0 0
Baseline

Eligibility
Key inclusion criteria
- At least 18 years of age (participants as young as 12 years of age will be allowed if
permitted by local regulatory authorities).

- Histologically or cytologically confirmed, unresectable, locally advanced and/or
metastatic MTC and no prior history of treatment with kinase inhibitors for
advanced/metastatic disease.

- Radiographic progressive disease per Response Evaluation Criteria in Solid Tumors
(RECIST) 1.1 at screening compared with a previous image taken within the prior 14
months as assessed by the BICR. Participants with measurable or non-measurable but
evaluable disease are eligible; however, participants with non-measurable disease may
not have disease limited to bone sites only.

- A defined/acceptable RET gene alteration identified in a tumor, germline
deoxyribonucleic acid (DNA) or blood sample.

- Tumor tissue in sufficient quantity to allow for retrospective central analysis
of RET mutation status

- Eastern Cooperative Oncology Group performance status score of 0 to 2.

- Adequate hematologic, hepatic, and renal function and electrolytes.

- Men and women of childbearing potential must agree to use a highly effective
contraceptive method during treatment with study drug and for 4 months following the
last dose of study drug.

- Ability to swallow capsules.
Minimum age
12 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- An additional validated oncogenic driver in MTC if known that could cause resistance
to selpercatinib treatment. Examples include, but are not limited to RAS or BRAF gene
mutations and NTRK gene fusions.

- Symptomatic central nervous system (CNS) metastases, leptomeningeal carcinomatosis, or
untreated spinal cord compression.

- Clinically significant active cardiovascular disease or history of myocardial
infarction within 6 months, history of Torsades de pointes, or prolongation of the
QTcF >470 milliseconds on more than one electrocardiogram (ECG) during screening.
Participants who are intended to receive vandetanib if randomized to the control arm
are ineligible if QTcF is >450 milliseconds.

- Active uncontrolled systemic bacterial, viral, or fungal infection or serious ongoing
uncontrolled intercurrent illness.

- Active hemorrhage or at significant risk for hemorrhage.

- Other malignancy unless nonmelanoma skin cancer, carcinoma in situ or malignancy
diagnosed =2 years previously and not currently active. Participants with multiple
endocrine neoplasia type 2 (MEN2) associated pheochromocytoma may be eligible.

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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
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
11/02/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
28/02/2026
Actual
Sample size
Target
Accrual to date
Final
291
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
Chris O'Brien Lifehouse - Camperdown
Recruitment hospital [2] 0 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [3] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [4] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [5] 0 0
Sir Charles Gairdner Hospital - Perth
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2065 - St Leonards
Recruitment postcode(s) [3] 0 0
3004 - Melbourne
Recruitment postcode(s) [4] 0 0
3050 - Melbourne
Recruitment postcode(s) [5] 0 0
6009 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
Michigan
Country [9] 0 0
United States of America
State/province [9] 0 0
Minnesota
Country [10] 0 0
United States of America
State/province [10] 0 0
Missouri
Country [11] 0 0
United States of America
State/province [11] 0 0
New York
Country [12] 0 0
United States of America
State/province [12] 0 0
Ohio
Country [13] 0 0
United States of America
State/province [13] 0 0
Oregon
Country [14] 0 0
United States of America
State/province [14] 0 0
Pennsylvania
Country [15] 0 0
United States of America
State/province [15] 0 0
Texas
Country [16] 0 0
United States of America
State/province [16] 0 0
Wisconsin
Country [17] 0 0
Belgium
State/province [17] 0 0
Antwerpen
Country [18] 0 0
Belgium
State/province [18] 0 0
Liège
Country [19] 0 0
Brazil
State/province [19] 0 0
Minas Gerais
Country [20] 0 0
Brazil
State/province [20] 0 0
Paraná
Country [21] 0 0
Brazil
State/province [21] 0 0
Rio Grande Do Sul
Country [22] 0 0
Brazil
State/province [22] 0 0
São Paulo
Country [23] 0 0
Brazil
State/province [23] 0 0
Rio de Janeiro
Country [24] 0 0
Canada
State/province [24] 0 0
Ontario
Country [25] 0 0
China
State/province [25] 0 0
Anhui
Country [26] 0 0
China
State/province [26] 0 0
Beijing
Country [27] 0 0
China
State/province [27] 0 0
Chongqing
Country [28] 0 0
China
State/province [28] 0 0
Fujian
Country [29] 0 0
China
State/province [29] 0 0
Gansu
Country [30] 0 0
China
State/province [30] 0 0
Guangdong
Country [31] 0 0
China
State/province [31] 0 0
Heilongjiang
Country [32] 0 0
China
State/province [32] 0 0
Henan
Country [33] 0 0
China
State/province [33] 0 0
Hunan
Country [34] 0 0
China
State/province [34] 0 0
Jiangsu
Country [35] 0 0
China
State/province [35] 0 0
Jilin
Country [36] 0 0
China
State/province [36] 0 0
Shandong
Country [37] 0 0
China
State/province [37] 0 0
Shanghai
Country [38] 0 0
China
State/province [38] 0 0
Sichuan
Country [39] 0 0
China
State/province [39] 0 0
Tianjin
Country [40] 0 0
China
State/province [40] 0 0
Yunnan
Country [41] 0 0
China
State/province [41] 0 0
Zhejiang
Country [42] 0 0
Czechia
State/province [42] 0 0
Brno-mesto
Country [43] 0 0
Czechia
State/province [43] 0 0
Praha 5
Country [44] 0 0
Czechia
State/province [44] 0 0
Olomouc
Country [45] 0 0
France
State/province [45] 0 0
Alsace
Country [46] 0 0
France
State/province [46] 0 0
Aquitaine
Country [47] 0 0
France
State/province [47] 0 0
Bouches-du-Rhône
Country [48] 0 0
France
State/province [48] 0 0
Calvados
Country [49] 0 0
France
State/province [49] 0 0
Côte-d'Or
Country [50] 0 0
France
State/province [50] 0 0
Haute-Garonne
Country [51] 0 0
France
State/province [51] 0 0
Maine-et-Loire
Country [52] 0 0
France
State/province [52] 0 0
Nord
Country [53] 0 0
France
State/province [53] 0 0
Orne
Country [54] 0 0
France
State/province [54] 0 0
Puy-de-Dôme
Country [55] 0 0
France
State/province [55] 0 0
Rhône-Alpes
Country [56] 0 0
France
State/province [56] 0 0
Val-de-Marne
Country [57] 0 0
Germany
State/province [57] 0 0
Bayern
Country [58] 0 0
Germany
State/province [58] 0 0
Niedersachsen
Country [59] 0 0
Germany
State/province [59] 0 0
Nordrhein-Westfalen
Country [60] 0 0
Germany
State/province [60] 0 0
Rheinland-Pfalz
Country [61] 0 0
Germany
State/province [61] 0 0
Sachsen-Anhalt
Country [62] 0 0
Germany
State/province [62] 0 0
Berlin
Country [63] 0 0
Germany
State/province [63] 0 0
Hamburg
Country [64] 0 0
Greece
State/province [64] 0 0
Attikí
Country [65] 0 0
Greece
State/province [65] 0 0
Irakleío
Country [66] 0 0
Greece
State/province [66] 0 0
Thessaloniki
Country [67] 0 0
India
State/province [67] 0 0
Kerala
Country [68] 0 0
India
State/province [68] 0 0
Maharashtra
Country [69] 0 0
India
State/province [69] 0 0
West Bengal
Country [70] 0 0
India
State/province [70] 0 0
Chandigarh
Country [71] 0 0
Israel
State/province [71] 0 0
HaMerkaz
Country [72] 0 0
Israel
State/province [72] 0 0
Yerushalayim
Country [73] 0 0
Italy
State/province [73] 0 0
Campania
Country [74] 0 0
Italy
State/province [74] 0 0
Lazio
Country [75] 0 0
Italy
State/province [75] 0 0
Lombardia
Country [76] 0 0
Italy
State/province [76] 0 0
Milano
Country [77] 0 0
Italy
State/province [77] 0 0
Piemonte
Country [78] 0 0
Italy
State/province [78] 0 0
Roma
Country [79] 0 0
Italy
State/province [79] 0 0
Toscana
Country [80] 0 0
Italy
State/province [80] 0 0
Veneto
Country [81] 0 0
Italy
State/province [81] 0 0
Catania
Country [82] 0 0
Japan
State/province [82] 0 0
Aichi
Country [83] 0 0
Japan
State/province [83] 0 0
Chiba
Country [84] 0 0
Japan
State/province [84] 0 0
Hokkaido
Country [85] 0 0
Japan
State/province [85] 0 0
Hyogo
Country [86] 0 0
Japan
State/province [86] 0 0
Kanagawa
Country [87] 0 0
Japan
State/province [87] 0 0
Osaka
Country [88] 0 0
Japan
State/province [88] 0 0
Tokyo
Country [89] 0 0
Japan
State/province [89] 0 0
Fukuoka
Country [90] 0 0
Korea, Republic of
State/province [90] 0 0
Chungcheongbuk-do [Chungbuk]
Country [91] 0 0
Korea, Republic of
State/province [91] 0 0
Korea
Country [92] 0 0
Korea, Republic of
State/province [92] 0 0
Kyonggi-do
Country [93] 0 0
Korea, Republic of
State/province [93] 0 0
Seoul-teukbyeolsi [Seoul]
Country [94] 0 0
Netherlands
State/province [94] 0 0
Limburg
Country [95] 0 0
Netherlands
State/province [95] 0 0
Noord-Holland
Country [96] 0 0
Netherlands
State/province [96] 0 0
Zuid-Holland
Country [97] 0 0
Netherlands
State/province [97] 0 0
Groningen
Country [98] 0 0
Poland
State/province [98] 0 0
Slaskie
Country [99] 0 0
Poland
State/province [99] 0 0
Swietokrzyskie
Country [100] 0 0
Russian Federation
State/province [100] 0 0
Chelyabinskaya Oblast'
Country [101] 0 0
Russian Federation
State/province [101] 0 0
Kalužskaja Oblast'
Country [102] 0 0
Russian Federation
State/province [102] 0 0
Moskva
Country [103] 0 0
Russian Federation
State/province [103] 0 0
Sankt-Peterburg
Country [104] 0 0
Spain
State/province [104] 0 0
Barcelona [Barcelona]
Country [105] 0 0
Spain
State/province [105] 0 0
Catalunya [Cataluña]
Country [106] 0 0
Spain
State/province [106] 0 0
Girona [Gerona]
Country [107] 0 0
Spain
State/province [107] 0 0
Madrid, Comunidad De
Country [108] 0 0
Spain
State/province [108] 0 0
Málaga
Country [109] 0 0
Spain
State/province [109] 0 0
Navarra
Country [110] 0 0
Spain
State/province [110] 0 0
Madrid
Country [111] 0 0
Spain
State/province [111] 0 0
Zaragoza
Country [112] 0 0
Taiwan
State/province [112] 0 0
Taichung
Country [113] 0 0
Taiwan
State/province [113] 0 0
Tainan
Country [114] 0 0
Taiwan
State/province [114] 0 0
Taipei
Country [115] 0 0
United Kingdom
State/province [115] 0 0
Cardiff [Caerdydd Gb-crd]
Country [116] 0 0
United Kingdom
State/province [116] 0 0
England
Country [117] 0 0
United Kingdom
State/province [117] 0 0
Glasgow City
Country [118] 0 0
United Kingdom
State/province [118] 0 0
Kensington And Chelsea
Country [119] 0 0
United Kingdom
State/province [119] 0 0
London, City Of
Country [120] 0 0
United Kingdom
State/province [120] 0 0
Surrey
Country [121] 0 0
United Kingdom
State/province [121] 0 0
Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Loxo Oncology, Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Eli Lilly and Company
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The reason for this study is to see if the study drug selpercatinib is safe and more
effective compared to a standard treatment in participants with rearranged during
transfection (RET)-mutant medullary thyroid cancer (MTC) that cannot be removed by surgery or
has spread to other parts of the body. Participants who are assigned to the standard
treatment and discontinue due to progressive disease have the option to potentially crossover
to selpercatinib.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04211337
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM
Address 0 0
Eli Lilly and Company
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/NCT04211337