Clinical trial NCT04721977: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Breast Cancer
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2021-01-25
Enrollment: 66
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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%.


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

Primary outcomes:
measure: Confirmed Objective Response Rate(cORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Determined by Independent Central Review (ICR): Japanese Participants
timeFrame: From date of first dose until first documented disease progression or start of new anticancer therapy, whichever occurred first (maximum up to 17.8 months)
Secondary outcomes:
measure: Confirmed Objective Response Rate(cORR) Per RECIST Version 1.1 Determined by ICR: All Participants
timeFrame: From date of first dose until first documented disease progression or start of new anticancer therapy, whichever occurred first
measure: Confirmed Objective Response Rate(cORR) Per RECIST Version 1.1 Determined by Investigator Assessment (INV): Japanese Participants
timeFrame: From date of first dose until first documented disease progression or start of new anticancer therapy, whichever occurred first
measure: Confirmed Objective Response Rate(cORR) Per RECIST Version 1.1 Determined by INV: All Participants
timeFrame: From date of first dose until first documented disease progression or start of new anticancer therapy, whichever occurred first
measure: Duration of Response (DOR) Per RECIST Version 1.1 Determined by INV: All Participants
timeFrame: From date of first objective response (CR or PR that is subsequently confirmed) to documented PD, or death from any cause whichever occurred first
measure: Duration of Response (DOR) Per RECIST Version 1.1 Determined by INV: Japanese Participants
timeFrame: From date of first objective response (CR or PR that is subsequently confirmed) to documented PD, or death from any cause whichever occurred first
measure: Duration of Response (DOR) Per RECIST Version 1.1 Determined by ICR: All Participants
timeFrame: From date of first objective response (CR or PR that is subsequently confirmed) to documented PD, or death from any cause whichever occurred first
measure: Duration of Response (DOR) Per RECIST Version 1.1 Determined by ICR: Japanese Participants
timeFrame: From date of first objective response (CR or PR that is subsequently confirmed) to documented PD, or death from any cause whichever occurred first
measure: Progression Free Survival (PFS) Per RECIST Version 1.1 Determined by ICR: All Participants
timeFrame: From date of first dose to the date of documented disease progression or death from any cause whichever occurred first or censoring date
measure: Progression Free Survival (PFS) Per RECIST Version 1.1 Determined by ICR: Japanese Participants
timeFrame: From date of first dose to the date of documented disease progression or death from any cause whichever occurred first or censoring date
measure: Progression Free Survival (PFS) Per RECIST Version 1.1 Determined by INV: All Participants
timeFrame: From date of first dose to the date of documented disease progression or death from any cause whichever occurred first or censoring date
measure: Progression Free Survival (PFS) Per RECIST Version 1.1 Determined by INV: Japanese Participants
timeFrame: From date of first dose to the date of documented disease progression or death from any cause whichever occurred first or censoring date
measure: Overall Survival: All Participants
timeFrame: From start of study treatment to date of death from any cause or censoring date
measure: Overall Survival: Japanese Participants
timeFrame: From start of study treatment to date of death from any cause or censoring date
measure: Number of Participants With Adverse Events, Serious Adverse Events and Treatment Related Adverse Events and Serious Adverse Events: All Participants
timeFrame: From date of first dose of study treatment to up to 30 days after last dose of study treatment
measure: Number of Participants With Adverse Events, Serious Adverse Events and Treatment Related Adverse Events and Serious Adverse Events: Japanese Participants
timeFrame: From date of first dose of study treatment to up to 30 days after last dose of study treatment
measure: Number of Participants With Abnormalities in Laboratory Parameters: All Participants
timeFrame: From date of first dose of study treatment to up to 30 days after last dose of study treatment
measure: Number of Participants With Abnormalities in Laboratory Parameters: Japanese Participants
timeFrame: From date of first dose of study treatment to up to 30 days after last dose of study treatment
measure: Number of Participants With Dose Modifications and Treatment Discontinuations: All Participants
timeFrame: From date of first dose of study treatment to up to 30 days after last dose of study treatment
measure: Number of Participants With Dose Modifications and Treatment Discontinuations: Japanese Participants
timeFrame: From date of first dose of study treatment to up to 30 days after last dose of study treatment
measure: Number of Participants With Clinically Significant Changes in Vital Signs: All Participants
timeFrame: From date of first dose of study treatment to up to 30 days after last dose of study treatment
measure: Number of Participants With Clinically Significant Changes in Vital Signs: Japanese Participants
timeFrame: From date of first dose of study treatment to up to 30 days after last dose of study treatment
Other outcomes:
Locations:
city: Nagoya
country: Japan
facility: Aichi Cancer Center Hospital ( Site 1013)
state: Aichi
city: Nagoya
country: Japan
facility: Nagoya University Hospital ( Site 1021)
state: Aichi
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East ( Site 1002)
state: Chiba
city: Matsuyama
country: Japan
facility: National Hospital Organization Shikoku Cancer Center ( Site 1014)
state: Ehime
city: Sapporo
country: Japan
facility: National Hospital Organization Hokkaido Cancer Center ( Site 1017)
state: Hokkaido
city: Sapporo
country: Japan
facility: Hokkaido University Hospital ( Site 1022)
state: Hokkaido
city: Akashi
country: Japan
facility: Hyogo Cancer Center ( Site 1005)
state: Hyogo
city: Nishinomiya
country: Japan
facility: Hyogo College of Medicine Hospital ( Site 1019)
state: Hyogo
city: Tsukuba
country: Japan
facility: University of Tsukuba Hospital ( Site 1020)
state: Ibaraki
city: Yokohama
country: Japan
facility: Kanagawa Cancer Center ( Site 1010)
state: Kanagawa
city: Naha
country: Japan
facility: Medical Corporation Nahanishikai Nahanishi Clinic ( Site 1016)
state: Okinawa
city: Kitaadachi-gun
country: Japan
facility: Saitama Cancer Center ( Site 1018)
state: Saitama
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Cancer Center ( Site 1009)
city: Fukushima
country: Japan
facility: Fukushima Medical University Hospital ( Site 1012)
city: Hiroshima
country: Japan
facility: Hiroshima City Hiroshima Citizens Hospital ( Site 1024)
city: Kagoshima
country: Japan
facility: Social medical corporation Hakuaikai Sagara Hospital ( Site 1008)
city: Kumamoto
country: Japan
facility: Kumamoto Shinto General Hospital ( Site 1007)
city: Osaka
country: Japan
facility: National Hospital Organization Osaka National Hospital ( Site 1001)
city: Osaka
country: Japan
facility: Osaka International Cancer Institute ( Site 1004)
city: Tokyo
country: Japan
facility: National Cancer Center Hospital ( Site 1003)
city: Tokyo
country: Japan
facility: Juntendo University Hospital ( Site 1025)
city: Tokyo
country: Japan
facility: The Cancer Institute Hospital of JFCR ( Site 1015)
city: Tokyo
country: Japan
facility: Showa University Hospital ( Site 1023)
city: Tokyo
country: Japan
facility: Tokyo Medical University Hospital ( Site 1006)
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital ( Site 2003)
city: Seoul
country: Korea, Republic of
facility: Severance Hospital ( Site 2001)
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center ( Site 2002)
city: Taiwan
country: Taiwan
facility: National Cheng Kung University Hospital ( Site 3000)
state: Tainan
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: