A Study of Tucatinib (ONT-380) Combined With Capecitabine and/or Trastuzumab in Patients With HER2+ Metastatic Breast Cancer
- Conditions
- HER2 Positive Metastatic Breast Cancers
- Interventions
- Registration Number
- NCT02025192
- Lead Sponsor
- Seagen Inc.
- Brief Summary
The purpose of this study is to determine the maximal tolerated dose (MTD) or recommended phase 2 dose (RP2D) of tucatinib (ONT-380) and to assess the safety and tolerability of tucatinib (ONT-380) combined with capecitabine alone, trastuzumab alone and with both capecitabine and trastuzumab in patients with HER2+ metastatic breast cancer.
- Detailed Description
This is a study of tucatinib (ONT-380) given in combination with capecitabine alone, trastuzumab alone and with both capecitabine and trastuzumab in patients with HER2+ metastatic breast cancer.
This study will use a 3+3 dose escalation design to evaluate escalating dose levels of tucatinib (ONT-380) in each of these three combinations in order to identify the maximal tolerated dose/recommended phase 2 dose (MTD/RP2D) of tucatinib (ONT-380). The MTD/RP2D of tucatinib (ONT-380) to be used in combination with either capecitabine alone (Combination 1) or trastuzumab alone (Combination 2) will be determined prior to evaluating tucatinib (ONT-380) in combination with both capecitabine and trastuzumab (Combination 3). If Combination 1 and Combination 2 are found to be tolerable, then tucatinib (ONT-380) will be evaluated in Combination 3, using the lowest MTD/RP2D or other SMC-recommended dose of tucatinib (ONT-380) determined for either of the two drug combinations. This will be followed by enrollment of an expansion cohort of patients treated at the MTD/RP2D for Combination 3. Additional expansion cohorts for either Combination 1 (tucatinib (ONT-380) and capecitabine) or Combination 2 (tucatinib (ONT-380) and trastuzumab) may also be enrolled.
Capecitabine will be given twice per day orally at 1000 mg/m\^2 on Days 1-14 of each 21-day cycle. Trastuzumab will be given as a loading dose of 8 mg/kg IV followed by 6 mg/kg once every 21 days. However, a loading dose of trastuzumab will not be given to patients who have received trastuzumab within 4 weeks of the first study dose of trastuzumab. These patients will receive trastuzumab at 6 mg/kg each cycle, including Cycle 1. Trastuzumab may also be given on a weekly basis at 2 mg/kg IV q 7 days, but only in the circumstance that trastuzumab infusion has been delayed, and weekly infusions are required to resynchronize the cycle length to 21 days, after discussion with the medical monitor. Trastuzumab infusion rates will be per institutional guidelines. Tucatinib (ONT-380) will be given twice per day orally at a dose dependent upon the dosing cohorts to which the patient is enrolled.
There will be 3-6 evaluable patients enrolled in each cohort in the dose escalation phase, unless that dose is found to be intolerable prior to completion of enrollment. At least 6 evaluable patients are to be treated at a dose level in order for an MTD/RP2D to be determined.
Provided that only seven dose cohorts are needed for dose escalation and only the expansion cohort for Combination 3 is enrolled, up to 66 evaluable patients may be enrolled. Additional patients may be enrolled if additional expansion cohorts are opened.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 60
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Tucatinib (ONT-380) in combination with capecitabine Tucatinib - Tucatinib (ONT-380) in combination with capecitabine Capecitabine - Tucatinib (ONT-380) in combination with trastuzumab Trastuzumab - Tucatinib (ONT-380) in combination with trastuzumab Tucatinib - Tucatinib (ONT-380) combined with capecitabine and trastuzumab Tucatinib - Tucatinib (ONT-380) combined with capecitabine and trastuzumab Capecitabine - Tucatinib (ONT-380) combined with capecitabine and trastuzumab Trastuzumab -
- Primary Outcome Measures
Name Time Method Incidence of adverse events Up to approximately 4 years Severity of adverse events Up to approximately 4 years
- Secondary Outcome Measures
Name Time Method Duration of response 26 months Incidence of clinical lab abnormalities (hematology, chemistry, liver function tests, coagulation, urinalysis) Up to approximately 4 years Severity of clinical lab abnormalities (hematology, chemistry, liver function tests, coagulation, urinalysis) Up to approximately 4 years Frequency of dose reductions in tucatinib (ONT-380 Up to approximately 4 years Frequency of dose reductions in capecitabine Up to approximately 4 years Plasma concentrations of tucatinib (ONT-380) and metabolite 26 months Plasma concentrations of capecitabine and metabolites 26 months Objective response rate (ORR) 26 months Objective response (OR) will be defined as a best response of complete response (CR) or partial response (PR). The ORR will be calculated as the proportion of patients in the Efficacy Evaluable Patient Set who achieve an objective response.
Disease control rate 26 months Disease control will be defined as a best response of CR, PR, or stable disease (SD). The DCR will be calculated as the proportion of patients in the Efficacy Evaluable Patient Set who achieve disease control.
Clinical benefit rate (CBR) 26 months Clinical benefit will be defined as a best response of CR, PR, or SD for ≥ 6 months. The CBR will be calculated as the proportion of patients in the Efficacy Evaluable Patient Set who achieve clinical benefit.
Progression-free survival (PFS) Up to 6 years PFS will be defined as the time from first dose of study drug until documentation of disease progression or death from any cause
Trial Locations
- Locations (5)
University of Colorado
🇺🇸Aurora, Colorado, United States
Northwest Medical Specialties
🇺🇸Tacoma, Washington, United States
Providence Cancer Center
🇺🇸Portland, Oregon, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States