Back to resultsA Study of Tucatinib (MK-7119) in Combination With Trastuzumab and Capecitabine in Participants With Previously Treated Locally Advanced Unresectable or Metastatic Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Breast Carcinoma (MK-7119-001)
Primary Purpose
Breast Cancer
Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Tucatinib
Trastuzumab
Capecitabine
Sponsored by
About this trial
This is an interventional treatment trial for Breast Cancer
Eligibility Criteria
Inclusion Criteria:
- Has histologically confirmed HER2+ breast carcinoma
- Has received previous treatment with taxane anti-cancer agent, trastuzumab, pertuzumab, and T-DM1 with the exception of when the use of taxanes is contraindicated or judged not to be the best treatment at the investigator's discretion
- Has radiographically and/or histologically confirmed disease progression on last systemic anticancer treatment
- Has adequate organ function
- Female participant is not pregnant or breastfeeding and is not a woman of childbearing potential (WOCBP) or is a WOCBP and using contraception or abstinent from heterosexual intercourse during the intervention period and for at least 30 days after receiving the last dose of tucatinib, 80 days after receiving the last dose of trastuzumab, or 180 days after receiving the last dose of capecitabine, whichever occurs last and agrees to not donate eggs during this period
- Male participants refrain from donating sperm and are either abstinent from heterosexual intercourse or agree to use contraception during the intervention period and for at least 7 days after receiving the last dose of tucatinib and 90 days after receiving the last dose of capecitabine, whichever occurs last
- Previously treated brain metastasis is stable or progressed, provided there is no clinical indication for immediate re-treatment
Exclusion Criteria:
- Has been previously treated with lapatinib within 12 months of starting study treatment
- Has been previously treated with neratinib, afatinib, tucatinib or capecitabine
- Has a history of exposure to doxorubicin, epirubicin, mitoxantrone, idarubicin, liposomal doxorubicin
- Has had treatment with any systemic anti-cancer therapy including hormonal therapy, non-central nervous system (CNS) radiation or experimental agent ≤3 weeks before first dose of study treatment
- Has any toxicity related to prior cancer therapies that has not resolved with the exception of alopecia, congestive heart failure, anemia
- Has clinically significant cardiopulmonary disease
- Has known myocardial infarction or unstable angina within 6 months prior to the first dose of study treatment
- Has any uncontrolled viral, bacterial or fungal infection within 14 days prior to the first dose of study treatment
- Is positive for Hepatitis B, Hepatitis C or has known chronic liver disease
- Is known to be positive for human immunodeficiency virus (HIV)
- Has evidence within 2 years of the start of study treatment of another malignancy that required systemic treatment
- Has ongoing use of systemic corticosteroids for control of symptoms of brain metastases
- Has any brain lesion thought to require immediate local therapy
- Has known or suspected leptomeningeal disease (LMD)
- Has poorly controlled generalized or complex partial seizures or manifest neurologic progression due to brain metastases
Sites / Locations
- Aichi Cancer Center Hospital ( Site 1013)
- Nagoya University Hospital ( Site 1021)
- National Cancer Center Hospital East ( Site 1002)
- National Hospital Organization Shikoku Cancer Center ( Site 1014)
- National Hospital Organization Hokkaido Cancer Center ( Site 1017)
- Hokkaido University Hospital ( Site 1022)
- Hyogo Cancer Center ( Site 1005)
- Hyogo College of Medicine Hospital ( Site 1019)
- University of Tsukuba Hospital ( Site 1020)
- Kanagawa Cancer Center ( Site 1010)
- Medical Corporation Nahanishikai Nahanishi Clinic ( Site 1016)
- Saitama Cancer Center ( Site 1018)
- National Hospital Organization Kyushu Cancer Center ( Site 1009)
- Fukushima Medical University Hospital ( Site 1012)
- Hiroshima City Hiroshima Citizens Hospital ( Site 1024)
- Social medical corporation Hakuaikai Sagara Hospital ( Site 1008)
- Kumamoto Shinto General Hospital ( Site 1007)
- National Hospital Organization Osaka National Hospital ( Site 1001)
- Osaka International Cancer Institute ( Site 1004)
- National Cancer Center Hospital ( Site 1003)
- Juntendo University Hospital ( Site 1025)
- The Cancer Institute Hospital of JFCR ( Site 1015)
- Showa University Hospital ( Site 1023)
- Tokyo Medical University Hospital ( Site 1006)
- Seoul National University Hospital ( Site 2003)
- Severance Hospital ( Site 2001)
- Samsung Medical Center ( Site 2002)
- National Cheng Kung University Hospital ( Site 3000)
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Tucatinib + Trastuzumab + Capecitabine
Arm Description
Participants will receive tucatinib plus trastuzumab plus capecitabine. Tucatinib 300 mg will be administered orally twice daily (BID). Trastuzumab 8 mg/kg loading dose followed by 6 mg/kg maintenance dose thereafter, will be administered intravenously (IV) on Day 1 of each 21-day cycle. Capecitabine 1000 mg/m^2 will be administered orally BID on Days 1-14 of each 21-day cycle. Tucatinib, trastuzumab and capecitabine treatment will continue until unacceptable toxicity, disease progression, death, withdrawal of consent or study closure.
Outcomes
Primary Outcome Measures
Confirmed Objective Response Rate (cORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1), as Determined by Independent Central Review (ICR)
cORR is defined as the percentage of participants who have a confirmed Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters) per RECIST v1.1. The percentage of participants who experience a confirmed CR or PR as determined by ICR based on RECIST v1.1 will be presented.
Secondary Outcome Measures
cORR per RECIST v1.1, as Determined by Investigator Assessment (INV)
cORR is defined as the percentage of participants who have a confirmed CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters) per RECIST v1.1. The percentage of participants who experience a confirmed CR or PR as determined by INV based on RECIST v1.1 will be presented.
Duration of Response (DOR) per RECIST v1.1, as Determined by ICR
For participants who demonstrate a confirmed CR (disappearance of all target lesions) or confirmed PR (at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters) per RECIST v1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST v1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The DOR as determined by ICR based on RECIST v1.1 will be presented.
DOR per RECIST v1.1, as Determined by INV
For participants who demonstrate a confirmed CR (disappearance of all target lesions) or confirmed PR (at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters) per RECIST v1.1, DOR is defined as the time from first documented evidence of CR or PR until PD or death due to any cause, whichever occurs first. Per RECIST v1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The DOR as determined by INV based on RECIST v1.1 will be presented.
Progression-free Survival (PFS) per RECIST v1.1, as Determined by ICR
PFS is defined as the time from randomization to the first documented PD or death due to any cause, whichever occurs first. Per RECIST v1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as determined by ICR based on RECIST v1.1 will be presented.
PFS per RECIST v1.1, as Determined by INV
PFS is defined as the time from randomization to the first documented PD or death due to any cause, whichever occurs first. Per RECIST v1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as determined by INV based on RECIST v1.1 will be presented.
Overall Survival (OS)
OS is defined as the time from start of study treatment to death due to any cause.
Number of Participants Who Experience One or More Adverse Events (AEs)
An AE is any untoward medical occurrence in a clinical investigation participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. The number of participants who experience one or more AEs will be presented.
Number of Participants who Discontinued Study Treatment Due to an AE
An AE is any untoward medical occurrence in a clinical investigation participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. The number of participants who discontinued study treatment due to an AE will be presented.
Full Information
NCT ID
NCT04721977
First Posted
January 20, 2021
Last Updated
July 21, 2023
Sponsor
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT04721977
Brief Title
A Study of Tucatinib (MK-7119) in Combination With Trastuzumab and Capecitabine in Participants With Previously Treated Locally Advanced Unresectable or Metastatic Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Breast Carcinoma (MK-7119-001)
Official Title
A Phase 2 Open-label, Single Arm Study of MK-7119 in Combination With Trastuzumab and Capecitabine in Participants With Previously Treated Locally Advanced Unresectable or Metastatic HER2+ Breast Carcinoma
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 8, 2021 (Actual)
Primary Completion Date
July 17, 2023 (Actual)
Study Completion Date
December 6, 2028 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. Study Description
Brief Summary
The goal of this study is to evaluate the efficacy and safety of tucatinib in combination with trastuzumab and capecitabine in participants with unresectable locally advanced or metastatic HER2+ breast cancer who have had prior treatment with taxane anti-cancer agent, trastuzumab, pertuzumab and trastuzumab emtansine (T-DM1). The primary hypothesis is that the confirmed objective response rate (cORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as determined by independent central review (ICR) for the combination of tucatinib, trastuzumab and capecitabine, is greater than 20%.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
66 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Tucatinib + Trastuzumab + Capecitabine
Arm Type
Experimental
Arm Description
Participants will receive tucatinib plus trastuzumab plus capecitabine. Tucatinib 300 mg will be administered orally twice daily (BID). Trastuzumab 8 mg/kg loading dose followed by 6 mg/kg maintenance dose thereafter, will be administered intravenously (IV) on Day 1 of each 21-day cycle. Capecitabine 1000 mg/m^2 will be administered orally BID on Days 1-14 of each 21-day cycle. Tucatinib, trastuzumab and capecitabine treatment will continue until unacceptable toxicity, disease progression, death, withdrawal of consent or study closure.
Intervention Type
Drug
Intervention Name(s)
Tucatinib
Other Intervention Name(s)
MK-7119, Tukysa
Intervention Description
Tucatinib 300 mg administered BID via oral tablet
Intervention Type
Biological
Intervention Name(s)
Trastuzumab
Other Intervention Name(s)
Herceptin, Herceptin Hylecta
Intervention Description
Trastuzumab 8 mg/kg loading dose followed by 6 mg/kg maintenance dose, administered via IV infusion
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Other Intervention Name(s)
Xeloda
Intervention Description
Capecitabine 1000 mg/m^2 administered BID via oral tablet
Primary Outcome Measure Information:
Title
Confirmed Objective Response Rate (cORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1), as Determined by Independent Central Review (ICR)
Description
cORR is defined as the percentage of participants who have a confirmed Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters) per RECIST v1.1. The percentage of participants who experience a confirmed CR or PR as determined by ICR based on RECIST v1.1 will be presented.
Time Frame
Up to ~21 months
Secondary Outcome Measure Information:
Title
cORR per RECIST v1.1, as Determined by Investigator Assessment (INV)
Description
cORR is defined as the percentage of participants who have a confirmed CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters) per RECIST v1.1. The percentage of participants who experience a confirmed CR or PR as determined by INV based on RECIST v1.1 will be presented.
Time Frame
Up to ~92 months
Title
Duration of Response (DOR) per RECIST v1.1, as Determined by ICR
Description
For participants who demonstrate a confirmed CR (disappearance of all target lesions) or confirmed PR (at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters) per RECIST v1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST v1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The DOR as determined by ICR based on RECIST v1.1 will be presented.
Time Frame
Up to ~92 months
Title
DOR per RECIST v1.1, as Determined by INV
Description
For participants who demonstrate a confirmed CR (disappearance of all target lesions) or confirmed PR (at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters) per RECIST v1.1, DOR is defined as the time from first documented evidence of CR or PR until PD or death due to any cause, whichever occurs first. Per RECIST v1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The DOR as determined by INV based on RECIST v1.1 will be presented.
Time Frame
Up to ~92 months
Title
Progression-free Survival (PFS) per RECIST v1.1, as Determined by ICR
Description
PFS is defined as the time from randomization to the first documented PD or death due to any cause, whichever occurs first. Per RECIST v1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as determined by ICR based on RECIST v1.1 will be presented.
Time Frame
Up to ~92 months
Title
PFS per RECIST v1.1, as Determined by INV
Description
PFS is defined as the time from randomization to the first documented PD or death due to any cause, whichever occurs first. Per RECIST v1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as determined by INV based on RECIST v1.1 will be presented.
Time Frame
Up to ~92 months
Title
Overall Survival (OS)
Description
OS is defined as the time from start of study treatment to death due to any cause.
Time Frame
Up to ~92 months
Title
Number of Participants Who Experience One or More Adverse Events (AEs)
Description
An AE is any untoward medical occurrence in a clinical investigation participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. The number of participants who experience one or more AEs will be presented.
Time Frame
Up to ~92 months
Title
Number of Participants who Discontinued Study Treatment Due to an AE
Description
An AE is any untoward medical occurrence in a clinical investigation participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. The number of participants who discontinued study treatment due to an AE will be presented.
Time Frame
Up to ~92 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Has histologically confirmed HER2+ breast carcinoma
Has received previous treatment with taxane anti-cancer agent, trastuzumab, pertuzumab, and T-DM1 with the exception of when the use of taxanes is contraindicated or judged not to be the best treatment at the investigator's discretion
Has radiographically and/or histologically confirmed disease progression on last systemic anticancer treatment
Has adequate organ function
Female participant is not pregnant or breastfeeding and is not a woman of childbearing potential (WOCBP) or is a WOCBP and using contraception or abstinent from heterosexual intercourse during the intervention period and for at least 30 days after receiving the last dose of tucatinib, 80 days after receiving the last dose of trastuzumab, or 180 days after receiving the last dose of capecitabine, whichever occurs last and agrees to not donate eggs during this period
Male participants refrain from donating sperm and are either abstinent from heterosexual intercourse or agree to use contraception during the intervention period and for at least 7 days after receiving the last dose of tucatinib and 90 days after receiving the last dose of capecitabine, whichever occurs last
Previously treated brain metastasis is stable or progressed, provided there is no clinical indication for immediate re-treatment
Exclusion Criteria:
Has been previously treated with lapatinib within 12 months of starting study treatment
Has been previously treated with neratinib, afatinib, tucatinib or capecitabine
Has a history of exposure to doxorubicin, epirubicin, mitoxantrone, idarubicin, liposomal doxorubicin
Has had treatment with any systemic anti-cancer therapy including hormonal therapy, non-central nervous system (CNS) radiation or experimental agent ≤3 weeks before first dose of study treatment
Has any toxicity related to prior cancer therapies that has not resolved with the exception of alopecia, congestive heart failure, anemia
Has clinically significant cardiopulmonary disease
Has known myocardial infarction or unstable angina within 6 months prior to the first dose of study treatment
Has any uncontrolled viral, bacterial or fungal infection within 14 days prior to the first dose of study treatment
Is positive for Hepatitis B, Hepatitis C or has known chronic liver disease
Is known to be positive for human immunodeficiency virus (HIV)
Has evidence within 2 years of the start of study treatment of another malignancy that required systemic treatment
Has ongoing use of systemic corticosteroids for control of symptoms of brain metastases
Has any brain lesion thought to require immediate local therapy
Has known or suspected leptomeningeal disease (LMD)
Has poorly controlled generalized or complex partial seizures or manifest neurologic progression due to brain metastases
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
Facility Information:
Facility Name
Aichi Cancer Center Hospital ( Site 1013)
City
Nagoya
State/Province
Aichi
ZIP/Postal Code
464-8681
Country
Japan
Facility Name
Nagoya University Hospital ( Site 1021)
City
Nagoya
State/Province
Aichi
ZIP/Postal Code
466-8560
Country
Japan
Facility Name
National Cancer Center Hospital East ( Site 1002)
City
Kashiwa
State/Province
Chiba
ZIP/Postal Code
2778577
Country
Japan
Facility Name
National Hospital Organization Shikoku Cancer Center ( Site 1014)
City
Matsuyama
State/Province
Ehime
ZIP/Postal Code
791-0280
Country
Japan
Facility Name
National Hospital Organization Hokkaido Cancer Center ( Site 1017)
City
Sapporo
State/Province
Hokkaido
ZIP/Postal Code
003-0804
Country
Japan
Facility Name
Hokkaido University Hospital ( Site 1022)
City
Sapporo
State/Province
Hokkaido
ZIP/Postal Code
060-8648
Country
Japan
Facility Name
Hyogo Cancer Center ( Site 1005)
City
Akashi
State/Province
Hyogo
ZIP/Postal Code
673-8558
Country
Japan
Facility Name
Hyogo College of Medicine Hospital ( Site 1019)
City
Nishinomiya
State/Province
Hyogo
ZIP/Postal Code
663-8501
Country
Japan
Facility Name
University of Tsukuba Hospital ( Site 1020)
City
Tsukuba
State/Province
Ibaraki
ZIP/Postal Code
305-8576
Country
Japan
Facility Name
Kanagawa Cancer Center ( Site 1010)
City
Yokohama
State/Province
Kanagawa
ZIP/Postal Code
241-8515
Country
Japan
Facility Name
Medical Corporation Nahanishikai Nahanishi Clinic ( Site 1016)
City
Naha
State/Province
Okinawa
ZIP/Postal Code
901-0154
Country
Japan
Facility Name
Saitama Cancer Center ( Site 1018)
City
Kitaadachi-gun
State/Province
Saitama
ZIP/Postal Code
362-0806
Country
Japan
Facility Name
National Hospital Organization Kyushu Cancer Center ( Site 1009)
City
Fukuoka
ZIP/Postal Code
811-1395
Country
Japan
Facility Name
Fukushima Medical University Hospital ( Site 1012)
City
Fukushima
ZIP/Postal Code
960-1295
Country
Japan
Facility Name
Hiroshima City Hiroshima Citizens Hospital ( Site 1024)
City
Hiroshima
ZIP/Postal Code
730-8518
Country
Japan
Facility Name
Social medical corporation Hakuaikai Sagara Hospital ( Site 1008)
City
Kagoshima
ZIP/Postal Code
892-0833
Country
Japan
Facility Name
Kumamoto Shinto General Hospital ( Site 1007)
City
Kumamoto
ZIP/Postal Code
862-8655
Country
Japan
Facility Name
National Hospital Organization Osaka National Hospital ( Site 1001)
City
Osaka
ZIP/Postal Code
540-0006
Country
Japan
Facility Name
Osaka International Cancer Institute ( Site 1004)
City
Osaka
ZIP/Postal Code
541-8567
Country
Japan
Facility Name
National Cancer Center Hospital ( Site 1003)
City
Tokyo
ZIP/Postal Code
104-0045
Country
Japan
Facility Name
Juntendo University Hospital ( Site 1025)
City
Tokyo
ZIP/Postal Code
113-0033
Country
Japan
Facility Name
The Cancer Institute Hospital of JFCR ( Site 1015)
City
Tokyo
ZIP/Postal Code
135-8550
Country
Japan
Facility Name
Showa University Hospital ( Site 1023)
City
Tokyo
ZIP/Postal Code
142-8666
Country
Japan
Facility Name
Tokyo Medical University Hospital ( Site 1006)
City
Tokyo
ZIP/Postal Code
160-0023
Country
Japan
Facility Name
Seoul National University Hospital ( Site 2003)
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Severance Hospital ( Site 2001)
City
Seoul
ZIP/Postal Code
03722
Country
Korea, Republic of
Facility Name
Samsung Medical Center ( Site 2002)
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Facility Name
National Cheng Kung University Hospital ( Site 3000)
City
Taiwan
State/Province
Tainan
ZIP/Postal Code
704
Country
Taiwan
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Links:
URL
https://www.merckclinicaltrials.com/
Description
Merck Clinical Trials Information
Learn more about this trial
A Study of Tucatinib (MK-7119) in Combination With Trastuzumab and Capecitabine in Participants With Previously Treated Locally Advanced Unresectable or Metastatic Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Breast Carcinoma (MK-7119-001)
We'll reach out to this number within 24 hrs