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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04776148




Registration number
NCT04776148
Ethics application status
Date submitted
26/02/2021
Date registered
1/03/2021

Titles & IDs
Public title
Study of Lenvatinib (MK-7902/E7080) in Combination With Pembrolizumab (MK-3475) Versus Standard of Care in Participants With Metastatic Colorectal Cancer (MK-7902-017/E7080-G000-325/LEAP-017)
Scientific title
A Phase 3 Randomized Study of Lenvatinib in Combination With Pembrolizumab Versus Standard of Care in Participants With Metastatic Colorectal Cancer Who Have Received and Progressed On or After or Became Intolerant to Prior Treatment
Secondary ID [1] 0 0
MK-7902-017
Secondary ID [2] 0 0
7902-017
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Colorectal Neoplasms 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - pembrolizumab
Treatment: Drugs - lenvatinib
Treatment: Drugs - regorafenib
Treatment: Drugs - TAS-102 (trifluridine and tipiracil)

Experimental: lenvatinib+pembrolizumab - Participants receive pembrolizumab 400 mg via intravenous (IV) infusion on Day 1 of each 6-week (Q6W) Cycle for up to 18 cycles (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily until progressive disease.

Active comparator: standard of care treatment (regorafenib OR TAS-102) - Participants receive regorafenib 160 mg via oral tablet once daily on Days 1 through 21 of each 4-week cycle OR TAS-102 (trifluridine and tipiracil hydrochloride) 35 mg/m\^2 via oral tablet twice a day on Days 1 through 5 and Days 8-12 of each 4-week cycle until progressive disease.


Treatment: Drugs: pembrolizumab
IV infusion

Treatment: Drugs: lenvatinib
oral capsule

Treatment: Drugs: regorafenib
oral tablet

Treatment: Drugs: TAS-102 (trifluridine and tipiracil)
oral tablet

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

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
Up to approximately 22 months
Secondary outcome [1] 0 0
Progression Free Survival (PFS) 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 22 months
Secondary outcome [2] 0 0
Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR
Timepoint [2] 0 0
Up to approximately 22 months
Secondary outcome [3] 0 0
Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR
Timepoint [3] 0 0
Up to approximately 22 months
Secondary outcome [4] 0 0
Number of Participants Who Experience an Adverse Event (AE)
Timepoint [4] 0 0
Up to approximately 22 months
Secondary outcome [5] 0 0
Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)
Timepoint [5] 0 0
Up to approximately 22 months
Secondary outcome [6] 0 0
Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score
Timepoint [6] 0 0
Baseline and 8 weeks
Secondary outcome [7] 0 0
Change From Baseline in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score
Timepoint [7] 0 0
Baseline and 8 weeks
Secondary outcome [8] 0 0
Change From Baseline in EORTC QLQ-C30 Appetite Loss (Item 13) Score
Timepoint [8] 0 0
Baseline and 8 weeks
Secondary outcome [9] 0 0
Change From Baseline in EORTC Quality of Life Questionnaire-Colorectal Cancer-Specific 29 Items (QLQ-CR29) Bloating (Item 37) Score
Timepoint [9] 0 0
Baseline and 8 weeks
Secondary outcome [10] 0 0
Time to Deterioration (TTD) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score
Timepoint [10] 0 0
Up to approximately 21 months
Secondary outcome [11] 0 0
TTD in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score
Timepoint [11] 0 0
Up to approximately 21 months
Secondary outcome [12] 0 0
TTD in EORTC QLQ-C30 Appetite Loss (Item 13) Score
Timepoint [12] 0 0
Up to approximately 21 months
Secondary outcome [13] 0 0
TTD in EORTC Quality of Life Questionnaire-Colorectal Cancer-Specific 29 Items (QLQ-CR29) Bloating (Item 37) Score
Timepoint [13] 0 0
Up to approximately 21 months

Eligibility
Key inclusion criteria
* Has histologically or cytologically confirmed diagnosis of unresectable and metastatic colorectal adenocarcinoma (Stage IV A, B and C as defined by American Joint Committee on Cancer [AJCC] 8th edition). Note: Tumor must be determined to be NOT microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) by local testing
* Has been previously treated for their disease and has shown disease progression as defined by RECIST 1.1 on or after or could not tolerate standard treatment, which must include ALL of the following agents if approved and locally available in the country where the participant is randomized:

1. fluoropyrimidine, irinotecan and oxaliplatin
2. with or without an anti-vascular endothelial growth factor (VEGF) monoclonal antibody (bevacizumab)
3. with anti- epidermal growth factor receptor (EGFR) monoclonal antibodies (cetuximab or panitumumab) for RAS (KRAS/NRAS) wild-type (WT) participants
4. BRAF inhibitor (in combination with cetuximab +/- binimetinib) for BRAF V600E mutated metastatic colon cancer (mCRC)
* Has measurable disease per RECIST 1.1 assessed by the investigator
* Has provided to a designated central laboratory an archival tumor tissue sample or newly obtained core, incisional, or excisional biopsy of a tumor lesion which has not been previously irradiated
* Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 3 days prior to randomization
* Has a life expectancy of at least 3 months, based on the investigator assessment
* Has the ability to swallow capsules or ingest a suspension orally or by a feeding tube
* Has adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP =150/90 millimeter of mercury (mmHg) with no change in antihypertensive medications within 1 week prior to randomization
* Male participants must agree to the following during the treatment period and for at least 90 days after the last dose of regorafenib or TAS-102 and at least 7 days after the last dose of lenvatinib: refrain from donating sperm PLUS either be abstinent from heterosexual intercourse as their preferred and usual lifestyle or use contraception. The male contraception period should continue for at least 7 days after discontinuation of lenvatinib
* A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: is not a woman of childbearing potential (WOCBP) OR is a WOCBP and using a highly-effective contraceptive method during the treatment period and for at least 30 days after the last dose of lenvatinib, 120 days after the last dose of pembrolizumab, and 180 days after the last dose of regorafenib or TAS-102 (whichever is last) AND agrees not to donate eggs (ova, oocytes)
* A WOCBP must have a negative highly sensitive pregnancy test (urine or serum) within 24 hours before the first dose of study treatment
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Has a tumor that is microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) per local testing
* Has presence of gastrointestinal condition, eg, malabsorption, that might affect the absorption of study drug.
* Has present or progressive accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks prior to enrollment
* Has radiographic evidence of encasement or invasion of a major blood vessel invasion or of intratumoral cavitation. In the chest, major blood vessels include the main pulmonary artery, the left and right pulmonary arteries, the 4 major pulmonary veins, the superior or inferior vena cava, and the aorta
* Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study drug
* Has clinically significant cardiovascular disease within 12 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability.

Participants with cardiac failure NYHA Class II, III and IV are not allowed to be assigned to the regorafenib in Arm B

* Has a history of arterial thromboembolism within 12 months of start of study drug
* Has urine protein =1 gram/24 hour
* Has prolongation of QT interval corrected with Fridericia's formula (QTcF interval) to >480 milliseconds
* Has left ventricular ejection fraction (LVEF) below the institutional (or local laboratory) normal range as determined by multigated acquisition (MUGA) or echocardiogram (ECHO)
* Has a known additional malignancy that is progressing or has required active treatment within the past 3 years with certain exceptions
* Has serious nonhealing wound, ulcer or bone fracture
* Has had major surgery within 3 weeks prior to first dose of study treatment
* Has received biologic response modifiers (eg, granulocyte colony-stimulating factor) within 4 weeks before study entry
* Has preexisting =Grade 3 gastrointestinal or nongastrointestinal fistula
* Has received prior treatment with a combination of an anti-PD-1, anti-PD-L1, or anti PD-L2 agent with anti-VEGF monoclonal antibodies or vascular endothelial growth factor receptor (VEGFR) inhibitors
* Has previously received regorafenib or TAS-102
* Has received prior systemic anti-cancer therapy including investigational agents within 28 days prior to randomization
* Has received prior radiotherapy within 2 weeks of start of study treatment
* Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study treatment
* Has known intolerance to lenvatinib, regorafenib, or TAS-102 and/or any of their excipients
* Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 28 days prior to the first dose of study treatment
* Has known central nervous system (CNS) metastases and/or carcinomatous meningitis.
* Has severe hypersensitivity (=Grade 3) to pembrolizumab and/or any of its excipients
* Has an active autoimmune disease that has required systemic treatment in past 2 years
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication
* Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
* Has an active infection requiring systemic therapy
* Has a known history of Human Immunodeficiency Virus (HIV) infection
* Has a known history of Hepatitis B or known active Hepatitis C virus 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 in the best interest of the participant to participate, in the opinion of the treating investigator
* Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study
* Has had an allogenic tissue/solid organ transplant

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)
QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Royal Brisbane and Women's Hospital-Medical Oncology Clinical Trials Unit, Cancer Care Services ( Si - Brisbane
Recruitment hospital [2] 0 0
Gallipoli Medical Research Foundation-GMRF CTU ( Site 1500) - Greenslopes
Recruitment hospital [3] 0 0
The Queen Elizabeth Hospital-Cancer Clinical Trials ( Site 1503) - Woodville
Recruitment hospital [4] 0 0
Epworth Freemasons ( Site 1506) - Melbourne
Recruitment hospital [5] 0 0
Western Health-Sunshine & Footscray Hospitals ( Site 1501) - St Albans
Recruitment hospital [6] 0 0
Hollywood Private Hospital-Medical Oncology ( Site 1507) - Perth
Recruitment postcode(s) [1] 0 0
4029 - Brisbane
Recruitment postcode(s) [2] 0 0
4120 - Greenslopes
Recruitment postcode(s) [3] 0 0
5011 - Woodville
Recruitment postcode(s) [4] 0 0
3002 - Melbourne
Recruitment postcode(s) [5] 0 0
3021 - St Albans
Recruitment postcode(s) [6] 0 0
6009 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Georgia
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
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
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
Montana
Country [7] 0 0
United States of America
State/province [7] 0 0
Oregon
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
Virginia
Country [10] 0 0
United States of America
State/province [10] 0 0
Washington
Country [11] 0 0
Argentina
State/province [11] 0 0
Buenos Aires
Country [12] 0 0
Argentina
State/province [12] 0 0
Caba
Country [13] 0 0
Argentina
State/province [13] 0 0
Santa Fe
Country [14] 0 0
Canada
State/province [14] 0 0
Alberta
Country [15] 0 0
Canada
State/province [15] 0 0
Nova Scotia
Country [16] 0 0
Canada
State/province [16] 0 0
Ontario
Country [17] 0 0
Canada
State/province [17] 0 0
Quebec
Country [18] 0 0
China
State/province [18] 0 0
Guangdong
Country [19] 0 0
China
State/province [19] 0 0
Zhejiang
Country [20] 0 0
Denmark
State/province [20] 0 0
Hovedstaden
Country [21] 0 0
Denmark
State/province [21] 0 0
Syddanmark
Country [22] 0 0
Germany
State/province [22] 0 0
Baden-Wurttemberg
Country [23] 0 0
Germany
State/province [23] 0 0
Bayern
Country [24] 0 0
Germany
State/province [24] 0 0
Nordrhein-Westfalen
Country [25] 0 0
Germany
State/province [25] 0 0
Berlin
Country [26] 0 0
Germany
State/province [26] 0 0
Hamburg
Country [27] 0 0
Israel
State/province [27] 0 0
Haifa
Country [28] 0 0
Israel
State/province [28] 0 0
Jerusalem
Country [29] 0 0
Israel
State/province [29] 0 0
Ramat Gan
Country [30] 0 0
Israel
State/province [30] 0 0
Tel Aviv
Country [31] 0 0
Japan
State/province [31] 0 0
Aichi
Country [32] 0 0
Japan
State/province [32] 0 0
Chiba
Country [33] 0 0
Japan
State/province [33] 0 0
Hyogo
Country [34] 0 0
Japan
State/province [34] 0 0
Kagawa
Country [35] 0 0
Japan
State/province [35] 0 0
Kanagawa
Country [36] 0 0
Japan
State/province [36] 0 0
Osaka
Country [37] 0 0
Japan
State/province [37] 0 0
Saitama
Country [38] 0 0
Japan
State/province [38] 0 0
Shizuoka
Country [39] 0 0
Japan
State/province [39] 0 0
Fukuoka
Country [40] 0 0
Japan
State/province [40] 0 0
Tokyo
Country [41] 0 0
Korea, Republic of
State/province [41] 0 0
Seoul
Country [42] 0 0
Russian Federation
State/province [42] 0 0
Baskortostan, Respublika
Country [43] 0 0
Russian Federation
State/province [43] 0 0
Leningradskaya Oblast
Country [44] 0 0
Russian Federation
State/province [44] 0 0
Moskva
Country [45] 0 0
Russian Federation
State/province [45] 0 0
Sverdlovskaya Oblast
Country [46] 0 0
Russian Federation
State/province [46] 0 0
Sankt-Peterburg
Country [47] 0 0
Spain
State/province [47] 0 0
Asturias
Country [48] 0 0
Spain
State/province [48] 0 0
Cantabria
Country [49] 0 0
Spain
State/province [49] 0 0
Barcelona
Country [50] 0 0
Spain
State/province [50] 0 0
Madrid
Country [51] 0 0
Spain
State/province [51] 0 0
Sevilla
Country [52] 0 0
Taiwan
State/province [52] 0 0
Taichung
Country [53] 0 0
Taiwan
State/province [53] 0 0
Tainan
Country [54] 0 0
Taiwan
State/province [54] 0 0
Taipei
Country [55] 0 0
Taiwan
State/province [55] 0 0
Taoyuan
Country [56] 0 0
Turkey
State/province [56] 0 0
Ankara
Country [57] 0 0
Turkey
State/province [57] 0 0
Edirne
Country [58] 0 0
Turkey
State/province [58] 0 0
Istanbul
Country [59] 0 0
Turkey
State/province [59] 0 0
Izmir
Country [60] 0 0
Turkey
State/province [60] 0 0
Malatya
Country [61] 0 0
United Kingdom
State/province [61] 0 0
Cambridgeshire
Country [62] 0 0
United Kingdom
State/province [62] 0 0
Essex
Country [63] 0 0
United Kingdom
State/province [63] 0 0
London, City Of
Country [64] 0 0
United Kingdom
State/province [64] 0 0
Midlothian
Country [65] 0 0
United Kingdom
State/province [65] 0 0
Surrey
Country [66] 0 0
United Kingdom
State/province [66] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck Sharp & Dohme LLC
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Eisai Inc.
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
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 Kawazoe A, Xu RH, Garcia-Alfonso P, Passhak M, Ten... [More Details]