Breast Neoplasms, Colorectal Cancer, Gastric or Gastroesophageal Junction Adenocarcinoma (GEC), Metastatic HER2+ Advanced Breast Cancer
Conditions
Brief summary
The primary purpose of this study is to characterize the safety and tolerability of tucatinib (MK-7119) in Chinese participants with human epidermal growth factor receptor 2 positive (HER2+) advanced breast cancer, gastric or gastroesophageal junction adenocarcinoma (GEC), and colorectal cancer.
Interventions
DRUGTucatinib
Tucatinib 150 mg and 50 mg tablets taken by mouth at a dose of 300 mg twice daily.
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed HER2+ advanced breast cancer, gastric or GEC, and colorectal cancer * Have progressed at least one previous therapeutic regimen and either no longer are candidates for standard therapy, have no standard therapy available, or choose not to pursue standard therapy * Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance within 7 days prior to allocation * Has life expectancy \>6 months in the opinion of the investigator * Have measurable disease per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 as assessed by the local site investigator/radiologist * Must test negative for hepatitis B surface antigen (HBsAg) * If there is a history of hepatitis C virus (HCV) infection, has undetectable HCV viral load at screening * For males, agree to be abstinent from heterosexual intercourse, or agree to use acceptable contraception, for the duration of study and 1 week after * For females, is not pregnant or breastfeeding AND one of the following applies: * Is not a woman of childbearing potential (WOCBP) * Is a WOCBP and uses highly effective contraception and is not pregnant
Exclusion criteria
* History of prior cancer within \<3 year, except for adequately treated basal cell or squamous cell carcinoma of the skin, cervical cancer in situ, or other in situ carcinomas which needs discussion between the investigator and the Sponsor * Participants with leptomeningeal disease are excluded * Has symptomatic central nervous system (CNS) metastases * Has active human immunodeficiency virus (HIV), hepatitis B virus, or HCV infection * Has had chemotherapy, immunotherapy, radioimmunotherapy, definitive radiation, or biological cancer therapy or treatment with an investigational product within 4 weeks (2 weeks for palliative radiation) before the first dose of study intervention * Has an active infection requiring therapy * Has refractory nausea/vomiting, chronic gastrointestinal disease, or significant bowel resection * Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study * Has a QTc prolongation * Has uncontrolled illness including but not limited to ongoing symptomatic congestive heart failure (New York Heart Association \[NYHA\] Class III or IV heart failure), unstable angina pectoris, cardiac arrhythmia, and psychiatric illness that would limit compliance with study requirements * Has had major surgery within 4 weeks prior to first dose of study intervention * Is currently participating in another clinical trial * Has psychiatric or substance abuse disorder
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of participants discontinuing from study therapy due to AE | Up to approximately 2.5 years | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. |
| Percentage of participants with ≥1 adverse event (AE) | Up to approximately 2.5 years | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum plasma concentration (Cmax) of first dose of tucatinib | Cycle 1, Day 1: predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose | The Cmax of tucatinib will be determined after the first dose. |
| Time of maximum plasma concentration (Tmax) of first dose of tucatinib | Cycle 1, Day 1: predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose | The Tmax of tucatinib will be determined after the first dose. |
| Area under the plasma concentration time curve from dosing to 12 hours postdose (AUC0-12) of first dose of tucatinib | Cycle 1, Day 1: predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose | The AUC0-12 of tucatinib will be determined after the first dose. |
| Apparent plasma half-life (t½) of first dose of tucatinib | Cycle 1, Day 1: predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose | The t½ of tucatinib will be determined after the first dose. |
| Apparent clearance (CL/F) of first dose of tucatinib | Cycle 1, Day 1: predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose | The CL/F of tucatinib will be determined after the first dose. |
| Volume of distribution (Vz/F) of first dose of tucatinib | Cycle 1, Day 1: predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose | The Vz/F of tucatinib will be determined after the first dose. |
| Trough concentration (Ctrough) of tucatinib at steady state | Cycle 1, Days 8 and 15: predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose | The Ctrough of tucatinib will be determined at steady state. |
| Accumulation ratio of tucatinib at steady state | Cycle 2, Day 1: predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose | The accumulation ratio of tucatinib will be determined at steady state. |
| Cmax at steady state (Cmaxss) of tucatinib | Cycle 2, Day 1: predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose | The Cmaxss of tucatinib will be determined at steady state. |
| Tmax at steady state (Tmaxss) of tucatinib | Cycle 2, Day 1: predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose | The Tmaxss of tucatinib will be determined at steady state. |
| AUC0-12 at steady state (AUC0-12ss) of tucatinib | Cycle 2, Day 1: predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose | The AUC0-12ss of tucatinib will be determined at steady state. |
| t½ of tucatinib at steady state | Cycle 2, Day 1: predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose | The t½ of tucatinib will be determined at steady state. |
| CL/F at steady state (CL/Fss) of tucatinib | Cycle 2, Day 1: predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose | The CL/Fss of tucatinib will be determined at steady state. |
| Vz/F at steady state (Vz/Fss) of tucatinib | Cycle 2, Day 1: predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose | The Vz/Fss of tucatinib will be determined at steady state. |
| Objective Response Rate (ORR) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) | Up to approximately 19 months | ORR is defined as the percentage of participants who have a 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) per RECIST 1.1. The percentage of participants who experience a CR or PR based on RECIST 1.1 will be presented. |
| Duration of Response (DOR) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) | Up to approximately 19 months | For participants who demonstrate a confirmed complete response (CR: Disappearance of all target lesions) or confirmed Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until disease progression or death. |
Countries
China
Contacts
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Outcome results
None listed