A Study of Tucatinib vs. Placebo in Combination With Capecitabine & Trastuzumab in Patients With Advanced HER2+ Breast Cancer
- Conditions
- HER2 Positive Breast Cancer
- Interventions
- Registration Number
- NCT02614794
- Lead Sponsor
- Seagen Inc.
- Brief Summary
This study is being done to see if tucatinib works better than placebo to help patients who have a specific type of breast cancer called HER2 positive breast carcinoma. The breast cancer in this study is either metastatic (spread into other parts of the body) or cannot be removed completely with surgery. All patients in the study will get capecitabine and trastuzumab, two drugs that are often used to treat this cancer.
There are two parts to this study. The first part of the study is already complete. Patients were randomly assigned to get either tucatinib or placebo (a pill with no medicine). Since this part was "blinded," neither patients nor their doctors knew whether a patient got tucatinib or placebo.
The second part of the study is called the Unblinded Phase. In this part of the study, participants and their doctors know which drugs are being given. Participants who used to get or are currently getting placebo may be able to start taking tucatinib instead.
Each treatment cycle lasts 21 days. Patients will swallow tucatinib pills two times every day. They will swallow capecitabine pills two times a day during the first two weeks of each cycle. Patients will get trastuzumab injections from the study site staff on the first day of every cycle.
- Detailed Description
This is a randomized, international, multi-center study in patients with progressive unresectable locally advanced or metastatic HER2+ breast cancer who have had prior treatment with trastuzumab, pertuzumab and T-DM1. There are two phases to this trial: the Double-blind Phase and the Unblinded Phase. In the Double-blind phase, participants were randomized in a 2:1 ratio to receive tucatinib or placebo in combination with capecitabine and trastuzumab. In the Unblinded Phase, patients on placebo may be offered tucatinib.
Stratification factors include presence or history of treated or untreated brain metastases or brain lesions of equivocal significance (yes/no), Eastern Cooperative Oncology Group (ECOG) Performance Status (0 vs. 1), and region of world (US vs. Canada vs. Rest of World).
Safety assessments will be performed at a minimum of once every three weeks throughout study treatment and 30 days after the last dose of study drugs. Laboratory assessments will be performed locally at sites. Left ventricular ejection fraction will be assessed by MUGA or ECHO at screening and once every 12 weeks thereafter.
For the blinded phase, contrast brain MRI was performed at baseline. Efficacy assessments (CT of chest, abdomen and pelvis at a minimum) utilized RECIST 1.1 and included patients with evaluable tumors defined as measurable target lesions and non-measurable non-target lesions. RECIST assessment was performed at baseline, every 6 weeks for the first 24 weeks, and then every 9 weeks thereafter. Repeat MRI of the brain was required on this same schedule only in those patients with brain metastases identified at baseline. All treatment decisions were made based upon investigator assessment. All patients underwent a repeat MRI of the brain within 30 days of the end of treatment unless previously performed at time of disease progression.
For the unblinded phase, RECIST assessments will be performed per standard clinical practice as determined by investigator with a maximum interval of 12 weeks.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 612
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo in combination with capecitabine & trastuzumab placebo Placebo + capecitabine + trastuzumab Tucatinib in combination with capecitabine & trastuzumab capecitabine Tucatinib + capecitabine + trastuzumab Tucatinib in combination with capecitabine & trastuzumab tucatinib Tucatinib + capecitabine + trastuzumab Tucatinib in combination with capecitabine & trastuzumab trastuzumab Tucatinib + capecitabine + trastuzumab Placebo in combination with capecitabine & trastuzumab trastuzumab Placebo + capecitabine + trastuzumab Placebo in combination with capecitabine & trastuzumab capecitabine Placebo + capecitabine + trastuzumab
- Primary Outcome Measures
Name Time Method Progression-free Survival (PFS) Per RECIST 1.1 as Determined by Blinded Independent Central Review (BICR) 34.6 months Defined as the time from the date of randomization to the date of documented disease progression.
- Secondary Outcome Measures
Name Time Method Frequency of Dose Modifications 35.1 months Pharmacokinetic Measure: Ctrough of Tucatinib 3.5 months Individual plasma tucatinib concentrations at each sampling time
Frequency of Dose Modifications at Time of Final Analysis Up to 60.1 months CBR Per RECIST 1.1 as Determined by Investigator Assessment 34.6 months Clinical benefit was defined as achieving stable disease (SD) or non-CR/non-PD for at least 6 months or a best overall response of confirmed CR or confirmed PR.
Incidence of Adverse Events (AEs) at Time of Primary Analysis 36.1 months As determined by assessment of AEs, clinical laboratory tests, and vital signs measurements. AEs were classified by system organ class (SOC) and preferred term using the Medical Dictionary for Regulatory Activities (MedDRA) Version 22.0 or higher; AE severities were classified using Version 4.03 of the (Common Terminology Criteria for Adverse Events) CTCAE criteria.
Incidence of Health Resources Utilization 36.1 months Cumulative incidence of health resource utilization, including length of stay, hospitalizations, and ER visits using the EQ-5D-5L questionnaire.
Overall Survival (OS) at Time of Final Analysis Up to 60.1 months Defined as time from randomization to death from any cause
PFS Per RECIST 1.1 as Determined by Investigator Assessment at Time of Final Analysis Up to 58.0 months Defined as the time from the date of randomization to the date of documented disease progression
PFS Per RECIST 1.1 as Determined by Investigator Assessment at Time of Primary Analysis 34.6 months Defined as the time from the date of randomization to the date of documented disease progression
Duration of Response (DOR) Per RECIST 1.1 as Determined by BICR 24.6 months Defined as the time from the first objective response to documented disease progression or death from any cause, whichever occurred first.
Incidence of Adverse Events (AEs) at Time of Final Analysis Up to 60.1 months As determined by assessment of AEs, clinical laboratory tests, and vital signs measurements. AEs were classified by system organ class (SOC) and preferred term using the Medical Dictionary for Regulatory Activities (MedDRA) Version 22.0 or higher; AE severities were classified using Version 4.03 of the (Common Terminology Criteria for Adverse Events) CTCAE criteria.
Confirmed Objective Response Rate (ORR) Per RECIST 1.1 as Determined by BICR 34.6 months Defined as achieving a best overall response of confirmed complete response (CR) or confirmed partial response (PR).
PFS in Patients With Brain Metastases at Baseline Using RECIST 1.1 as Determined by BICR 34.6 months Defined as the time from the date of randomization to the date of documented disease progression.
Overall Survival (OS) at Time of Primary Analysis 35.9 months Defined as time from randomization to death from any cause
DOR Per RECIST 1.1 as Determined by Investigator Assessment 33.2 months Defined as the time from the first objective response to documented disease progression or death from any cause, whichever occurred first.
ORR Per RECIST 1.1 as Determined by Investigator Assessment 34.6 months Defined as achieving a best overall response of confirmed CR or confirmed PR.
Clinical Benefit Rate (CBR) as Determined by BICR Per RECIST 1.1 34.6 months Clinical benefit was defined as achieving stable disease (SD) or non-complete response (CR)/non-progressive disease (PD) for at least 6 months or a best overall response of confirmed CR or confirmed partial response (PR).
Pharmacokinetic Measure: ONT-993 3.5 months Individual plasma primary metabolite concentrations at each sampling time
Trial Locations
- Locations (176)
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
University of South Alabama - Mitchell Cancer Institute
🇺🇸Mobile, Alabama, United States
Cancer Treatment Centers of America - Phoenix
🇺🇸Goodyear, Arizona, United States
Arizona Oncology Associates, PC - HAL
🇺🇸Phoenix, Arizona, United States
City of Hope National Medical Center
🇺🇸Duarte, California, United States
TRIO - Central Regulatory Office
🇺🇸Los Angeles, California, United States
UCLA Medical Center / David Geffen School of Medicine
🇺🇸Los Angeles, California, United States
Torrance Memorial Physician Network - TRIO
🇺🇸Redondo Beach, California, United States
University of California at San Francisco
🇺🇸San Francisco, California, United States
Kaiser Permanente San Marcos Medical Offices
🇺🇸San Marcos, California, United States
Scroll for more (166 remaining)University of Alabama at Birmingham🇺🇸Birmingham, Alabama, United States