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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04489771




Registration number
NCT04489771
Ethics application status
Date submitted
27/07/2020
Date registered
28/07/2020

Titles & IDs
Public title
A Study of Belzutifan (MK-6482) in Participants With Advanced Renal Cell Carcinoma (MK-6482-013)
Scientific title
Phase 2 Study of MK-6482 in Participants With Advanced Renal Cell Carcinoma
Secondary ID [1] 0 0
MK-6482-013
Secondary ID [2] 0 0
6482-013
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Carcinoma, Renal Cell 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Belzutifan

Experimental: Belzutifan 200 mg - Participants receive 200 mg of belzutifan by oral administration, once a day (QD), until disease progression or discontinuation.

Experimental: Belzutifan 120 mg - Participants receive 120 mg of belzutifan by oral administration, QD, until disease progression or discontinuation.


Treatment: Drugs: Belzutifan
Oral administration
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
Timepoint [1] 0 0
Up to approximately 27 months
Secondary outcome [1] 0 0
Progression-Free Survival (PFS) According to RECIST 1.1 as Assessed by BICR
Timepoint [1] 0 0
Up to approximately 27 months
Secondary outcome [2] 0 0
Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR
Timepoint [2] 0 0
Up to approximately 27 months
Secondary outcome [3] 0 0
Clinical Benefit Rate (CBR) Per RECIST 1.1 as Assessed by BICR
Timepoint [3] 0 0
Up to approximately 27 months
Secondary outcome [4] 0 0
Overall Survival (OS)
Timepoint [4] 0 0
Up to approximately 27 months
Secondary outcome [5] 0 0
Number of Participants Who Experience One or More Adverse Events (AEs)
Timepoint [5] 0 0
Up to approximately 27 months
Secondary outcome [6] 0 0
Number of Participants Who Discontinue Study Treatment Due to an AE
Timepoint [6] 0 0
Up to approximately 26 months
Secondary outcome [7] 0 0
Maximum Plasma Concentration (Cmax) of Belzutifan
Timepoint [7] 0 0
Weeks 1 and 3 on Day 1: predose and 1, 2, and 4 hours. Week 5 on Day 1: predose only
Secondary outcome [8] 0 0
Trough Plasma Concentration (Ctrough) of Belzutifan
Timepoint [8] 0 0
Weeks 1 and 3 on Day 1: predose and 1, 2, and 4 hours. Week 5 on Day 1: predose only

Eligibility
Key inclusion criteria
* Has a histologically confirmed diagnosis of locally advanced/metastatic RCC with clear cell component
* Has measurable disease per RECIST 1.1 as assessed by BICR
* Can submit an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
* Has experienced disease progression on or after systemic treatment with an anti-programmed cell death 1 (PD-1)/Ligand 1 (L1) therapy for locally advanced or metastatic RCC. The anti-PD-1/L1 therapy may be monotherapy or in combination with other agent(s) such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) or vascular endothelial growth factor (VEGF) targeted- tyrosine kinase inhibitor (TKI). The immediately preceding line of treatment has to have been an anti-PD-1/L1 therapy
* Has received no more than 3 prior systemic regimens for locally advanced or metastatic RCC
* Has received only 1 prior anti-PD-1/L1 therapy for locally advanced or metastatic RCC
* Has recovered from all AEs due to previous therapies to =Grade 1 or baseline, with the exception of =Grade 2 neuropathy or endocrine-related AEs =Grade 2 requiring treatment or hormone replacement
* Has a Karnofsky performance status (KPS) score of at least 70% assessed within 10 days prior to the first dose of study intervention
* A male participant is eligible to participate if he is abstinent from heterosexual intercourse or agrees to use contraception during the intervention period and for at least 7 days after the last dose of study intervention
* A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies: Not a (woman of childbearing potential) WOCBP or a WOCBP who agrees to follow the contraceptive guidance during the intervention period and for at least 30 days after the last dose of study intervention
* A WOCBP must have a negative highly sensitive pregnancy test (urine or serum) within 24 hours before the first dose of study intervention
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Has hypoxia (a pulse oximeter reading <92% at rest), requires intermittent supplemental oxygen, or requires chronic supplemental oxygen
* Has a known additional malignancy that is progressing or has required active treatment within the past 3 years except for basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ [e.g., breast carcinoma, cervical cancer in situ] that have undergone potentially curative therapy
* Has known central nervous system (CNS) metastases and/or carcinomatous meningitis
* Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction =6 months from Day 1 of study drug administration or New York Heart Association Class III or IV congestive heart failure
* Has moderate to severe hepatic impairment (Child-Pugh B or C)
* Has received colony-stimulating factors (eg, granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor [GM-CSF], or recombinant erythropoietin [EPO]) =28 days prior to the first dose of study intervention
* Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study
* Is unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption (eg, gastrectomy, partial bowel obstruction, malabsorption)
* Has known hypersensitivity or allergy to the active pharmaceutical ingredient or any component of the study intervention (belzutifan) formulations
* Has received prior treatment with belzutifan or another hypoxia-inducible factor (HIF)-2a inhibitor
* Has received any type of small molecule kinase inhibitor (including investigational kinase inhibitor) =2 weeks before randomization
* Has received any type of systemic anticancer antibody (including investigational antibody) =4 weeks before randomization
* Has received prior radiotherapy =2 weeks prior to first dose of study intervention. Participants must have recovered from all radiation-related toxicities and not require corticosteroids
* Has had major surgery =3 weeks prior to first dose of study intervention
* Is currently receiving either strong (phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate (eg, bosentan, efavirenz, modafinil) inducers of cytochrome P450 (CYP)3A4 that cannot be discontinued for the duration of the study
* Is currently participating in a study of an investigational agent or is currently using an investigational device
* Has an active infection requiring systemic therapy
* Has active tuberculosis (TB)
* Has a diagnosis of immunodeficiency
* Has a known history of human immunodeficiency virus (HIV) infection
* Has a known history of hepatitis B (HBV) or known active hepatitis C (HCV) infection
* Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not the best interest of the participant to participate, in the opinion of the treating investigator

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 2
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
13/09/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
4/10/2025
Actual
Sample size
Target
Accrual to date
Final
154
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Macquarie University ( Site 1007) - Macquarie University
Recruitment hospital [2] 0 0
Eastern Health - Box Hill Hospital ( Site 1003) - Box Hill
Recruitment hospital [3] 0 0
Peninsula Health Frankston Hospital ( Site 1001) - Frankston
Recruitment postcode(s) [1] 0 0
2109 - Macquarie University
Recruitment postcode(s) [2] 0 0
3128 - Box Hill
Recruitment postcode(s) [3] 0 0
3199 - Frankston
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
District of Columbia
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Kentucky
Country [4] 0 0
United States of America
State/province [4] 0 0
Maryland
Country [5] 0 0
United States of America
State/province [5] 0 0
Nebraska
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Pennsylvania
Country [8] 0 0
United States of America
State/province [8] 0 0
South Dakota
Country [9] 0 0
United States of America
State/province [9] 0 0
Tennessee
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
United States of America
State/province [11] 0 0
Utah
Country [12] 0 0
United States of America
State/province [12] 0 0
Virginia
Country [13] 0 0
United States of America
State/province [13] 0 0
Washington
Country [14] 0 0
Belgium
State/province [14] 0 0
Antwerpen
Country [15] 0 0
Belgium
State/province [15] 0 0
Hainaut
Country [16] 0 0
Belgium
State/province [16] 0 0
Liege
Country [17] 0 0
Belgium
State/province [17] 0 0
Oost-Vlaanderen
Country [18] 0 0
Belgium
State/province [18] 0 0
Vlaams-Brabant
Country [19] 0 0
Greece
State/province [19] 0 0
Attiki
Country [20] 0 0
Greece
State/province [20] 0 0
Thessalia
Country [21] 0 0
Ireland
State/province [21] 0 0
Cork
Country [22] 0 0
Ireland
State/province [22] 0 0
Dublin
Country [23] 0 0
Israel
State/province [23] 0 0
Beer Sheva
Country [24] 0 0
Israel
State/province [24] 0 0
Haifa
Country [25] 0 0
Israel
State/province [25] 0 0
Petach Tikva
Country [26] 0 0
Israel
State/province [26] 0 0
Tel Aviv
Country [27] 0 0
Netherlands
State/province [27] 0 0
Limburg
Country [28] 0 0
Netherlands
State/province [28] 0 0
Noord-Holland
Country [29] 0 0
Netherlands
State/province [29] 0 0
Overijssel
Country [30] 0 0
Netherlands
State/province [30] 0 0
Zuid-Holland
Country [31] 0 0
Netherlands
State/province [31] 0 0
Utrecht
Country [32] 0 0
Russian Federation
State/province [32] 0 0
Moskva
Country [33] 0 0
Russian Federation
State/province [33] 0 0
Sankt-Peterburg
Country [34] 0 0
United Kingdom
State/province [34] 0 0
England
Country [35] 0 0
United Kingdom
State/province [35] 0 0
London, City Of
Country [36] 0 0
United Kingdom
State/province [36] 0 0
Oxfordshire
Country [37] 0 0
United Kingdom
State/province [37] 0 0
Nottingham

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck Sharp & Dohme LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
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?
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://engagezone.msd.com/ds_documentation.php


What supporting documents are/will be available?




Results publications and other study-related documents

TypeCitations or Other Details
Journal Agarwal N, Brugarolas J, Ghatalia P, George S, Haa... [More Details]


Results are available at https://clinicaltrials.gov/study/NCT04489771