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)

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04721977
• Other study ID #: 7119-001
• Secondary ID: MK-7119-001jRCT2
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: April 8, 2021
• Est. completion date: December 6, 2028

Study information

• Verified date: May 2024
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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%.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 66
• Est. completion date: December 6, 2028
• Est. primary completion date: July 17, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Tucatinib
Tucatinib 300 mg administered BID via oral tablet

Biological:
• Trastuzumab
Trastuzumab 8 mg/kg loading dose followed by 6 mg/kg maintenance dose, administered via IV infusion

Drug:
• Capecitabine
Capecitabine 1000 mg/m^2 administered BID via oral tablet

Locations

Country	Name	City	State
Japan	Hyogo Cancer Center ( Site 1005)	Akashi	Hyogo
Japan	National Hospital Organization Kyushu Cancer Center ( Site 1009)	Fukuoka
Japan	Fukushima Medical University Hospital ( Site 1012)	Fukushima
Japan	Hiroshima City Hiroshima Citizens Hospital ( Site 1024)	Hiroshima
Japan	Social medical corporation Hakuaikai Sagara Hospital ( Site 1008)	Kagoshima
Japan	National Cancer Center Hospital East ( Site 1002)	Kashiwa	Chiba
Japan	Saitama Cancer Center ( Site 1018)	Kitaadachi-gun	Saitama
Japan	Kumamoto Shinto General Hospital ( Site 1007)	Kumamoto
Japan	National Hospital Organization Shikoku Cancer Center ( Site 1014)	Matsuyama	Ehime
Japan	Aichi Cancer Center Hospital ( Site 1013)	Nagoya	Aichi
Japan	Nagoya University Hospital ( Site 1021)	Nagoya	Aichi
Japan	Medical Corporation Nahanishikai Nahanishi Clinic ( Site 1016)	Naha	Okinawa
Japan	Hyogo College of Medicine Hospital ( Site 1019)	Nishinomiya	Hyogo
Japan	National Hospital Organization Osaka National Hospital ( Site 1001)	Osaka
Japan	Osaka International Cancer Institute ( Site 1004)	Osaka
Japan	Hokkaido University Hospital ( Site 1022)	Sapporo	Hokkaido
Japan	National Hospital Organization Hokkaido Cancer Center ( Site 1017)	Sapporo	Hokkaido
Japan	Juntendo University Hospital ( Site 1025)	Tokyo
Japan	National Cancer Center Hospital ( Site 1003)	Tokyo
Japan	Showa University Hospital ( Site 1023)	Tokyo
Japan	The Cancer Institute Hospital of JFCR ( Site 1015)	Tokyo
Japan	Tokyo Medical University Hospital ( Site 1006)	Tokyo
Japan	University of Tsukuba Hospital ( Site 1020)	Tsukuba	Ibaraki
Japan	Kanagawa Cancer Center ( Site 1010)	Yokohama	Kanagawa
Korea, Republic of	Samsung Medical Center ( Site 2002)	Seoul
Korea, Republic of	Seoul National University Hospital ( Site 2003)	Seoul
Korea, Republic of	Severance Hospital ( Site 2001)	Seoul
Taiwan	National Cheng Kung University Hospital ( Site 3000)	Taiwan	Tainan

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

Japan,  Korea, Republic of,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to ~21 months
Secondary	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.	Up to ~92 months
Secondary	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.	Up to ~92 months
Secondary	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.	Up to ~92 months
Secondary	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.	Up to ~92 months
Secondary	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.	Up to ~92 months
Secondary	Overall Survival (OS)	OS is defined as the time from start of study treatment to death due to any cause.	Up to ~92 months
Secondary	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.	Up to ~92 months
Secondary	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.	Up to ~92 months

External Links

•   Merck Clinical Trials Information