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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT04211337
Ethics application status
Date submitted
24/12/2019
Date registered
26/12/2019

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 - Treatment A (TRT A) - 160 milligrams Selpercatinib administered orally (PO) twice daily (BID).

Adolescent Dose: 92 milligrams per square meter (mg/m2) BID (not to exceed 160 mg BID).

Active comparator: Cabozantinib or Vandetanib - Treatment B (TRT B) - 140 mg Cabozantinib administered orally daily (QD) or 300 mg Vandetanib administered orally QD per physician choice.

Cabozantinib Adolescent Dose: 40 mg/m2.

Vandetanib Adolescent Dose:

* 0.7 - \<0.9 - 100 mg every other day (QOD)
* 0.9 - \<1.2 - 100 mg QD
* 1.2 - \<1.6 - 7-day schedule 100 mg - 200 mg - 100 mg - 200 mg - 100 mg - 200 mg - 100 mg
* =1.6 - 200 QD


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 Blinded Independent Central Review (BICR)
Timepoint [1] 0 0
Baseline to Progressive Disease or Death from Any Cause, Whichever Occurs First, Up to 35 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 Up to 35 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 up to 35 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 Up to 33 Months
Secondary outcome [4] 0 0
Overall Survival (OS)
Timepoint [4] 0 0
Baseline to Date of Death from Any Cause Up to 36 Months
Secondary outcome [5] 0 0
PFS2 by Investigator
Timepoint [5] 0 0
Baseline to Second Disease Progression or Death from Any Cause Up to 35 Months
Secondary outcome [6] 0 0
Comparative Tolerability: Number of Weeks With High Side Effect Bother Based Score of 3 or 4 on the Functional Assessment of Cancer Therapy Item GP5 (FACT-GP5)
Timepoint [6] 0 0
Baseline to Progressive Disease, Unacceptable Toxicity or Death from Any Cause Up to 35 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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [2] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [3] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [4] 0 0
Sir Charles Gairdner Hospital - Perth
Recruitment postcode(s) [1] 0 0
2065 - St Leonards
Recruitment postcode(s) [2] 0 0
3004 - Melbourne
Recruitment postcode(s) [3] 0 0
3050 - Melbourne
Recruitment postcode(s) [4] 0 0
6009 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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United States of America
State/province [2] 0 0
California
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United States of America
State/province [3] 0 0
Georgia
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United States of America
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Illinois
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United States of America
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Massachusetts
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United States of America
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Michigan
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New York
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Ohio
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United States of America
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Pennsylvania
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United States of America
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Texas
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United States of America
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Wisconsin
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Belgium
State/province [12] 0 0
Liège
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Brazil
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Minas Gerais
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Brazil
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Paraná
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Brazil
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Rio Grande Do Sul
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Brazil
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São Paulo
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Brazil
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Rio de Janeiro
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Canada
State/province [18] 0 0
Ontario
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China
State/province [19] 0 0
Anhui
Country [20] 0 0
China
State/province [20] 0 0
Beijing
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China
State/province [21] 0 0
Chongqing
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China
State/province [22] 0 0
Fujian
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China
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Gansu
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China
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Guangdong
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China
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Heilongjiang
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China
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Henan
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China
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Hunan
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Jiangsu
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China
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Jilin
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Shandong
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Shanghai
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Tianjin
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Yunnan
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China
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Zhejiang
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Czechia
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Brno-mesto
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Czechia
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Praha 5
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Czechia
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Olomouc
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France
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Alsace
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Aquitaine
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Côte-d'Or
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France
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Maine-et-Loire
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France
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Nord
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France
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Orne
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France
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Puy-de-Dôme
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France
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Rhône-Alpes
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France
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Val-de-Marne
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Germany
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Bayern
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Germany
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Niedersachsen
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Germany
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Nordrhein-Westfalen
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Germany
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Rheinland-Pfalz
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Germany
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Sachsen-Anhalt
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Germany
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Berlin
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Germany
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Hamburg
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Greece
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Attikí
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Greece
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Irakleío
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Greece
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Thessaloniki
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India
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Kerala
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India
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Maharashtra
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India
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West Bengal
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Chandigarh
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Israel
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HaMerkaz
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Israel
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Yerushalayim
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Italy
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Campania
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Lazio
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Lombardia
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Milano
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Piemonte
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Roma
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Toscana
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Veneto
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Catania
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Aichi
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Chiba
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Hokkaido
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Hyogo
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Japan
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Fukuoka
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Korea, Republic of
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Chungcheongbuk-do [Chungbuk]
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Korea, Republic of
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Kyonggi-do
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Korea, Republic of
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Seoul-teukbyeolsi [Seoul]
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Netherlands
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Limburg
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Netherlands
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Noord-Holland
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Netherlands
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Zuid-Holland
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Netherlands
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Groningen
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Poland
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Slaskie
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Poland
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Swietokrzyskie
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Russian Federation
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Chelyabinskaya Oblast'
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Russian Federation
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Kalužskaja Oblast'
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Russian Federation
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Moskva
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Russian Federation
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Sankt-Peterburg
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Spain
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Barcelona [Barcelona]
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Spain
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Catalunya [Cataluña]
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Spain
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Girona [Gerona]
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Spain
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Madrid, Comunidad De
Country [101] 0 0
Spain
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Málaga
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Spain
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Navarra
Country [103] 0 0
Spain
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Madrid
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Spain
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Zaragoza
Country [105] 0 0
United Kingdom
State/province [105] 0 0
Cardiff [Caerdydd Gb-crd]
Country [106] 0 0
United Kingdom
State/province [106] 0 0
England
Country [107] 0 0
United Kingdom
State/province [107] 0 0
Glasgow City
Country [108] 0 0
United Kingdom
State/province [108] 0 0
Kensington And Chelsea
Country [109] 0 0
United Kingdom
State/province [109] 0 0
London, City Of
Country [110] 0 0
United Kingdom
State/province [110] 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
Trial website
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Clinical study report (CSR)
When will data be available (start and end dates)?
Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
Available to whom?
A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://vivli.org/


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.