A Study of Tucatinib vs. Placebo in Combination With Capecitabine & Trastuzumab in Patients With Advanced HER2+ Breast Cancer

Official Title

Phase 2 Randomized, Double-Blinded, Controlled Study of Tucatinib vs Placebo in Combination With Capecitabine and Trastuzumab in Patients With Pretreated Unresectable Locally Advanced or Metastatic HER2+ Breast Carcinoma


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.

Trial Description

Primary Outcome:

  • Progression-free Survival (PFS) Per RECIST 1.1 as Determined by Blinded Independent Central Review (BICR)
Secondary Outcome:
  • PFS in Patients With Brain Metastases at Baseline Using RECIST 1.1 as Determined by BICR
  • Overall Survival (OS)
  • Confirmed Objective Response Rate (ORR) Per RECIST 1.1 as Determined by BICR
  • ORR Per RECIST 1.1 as Determined by Investigator Assessment
  • PFS Per RECIST 1.1 as Determined by Investigator Assessment
  • Duration of Response (DOR) Per RECIST 1.1 as Determined by BICR
  • DOR Per RECIST 1.1 as Determined by Investigator Assessment
  • Clinical Benefit Rate (CBR) as Determined by BICR Per RECIST 1.1
  • CBR Per RECIST 1.1 as Determined by Investigator Assessment
  • Incidence of Adverse Events (AEs)
  • Frequency of Dose Modifications
  • Incidence of Health Resources Utilization
  • Pharmacokinetic Measure: Ctrough of Tucatinib
  • Pharmacokinetic Measure: ONT-993
This is a randomized, international, multi-centre 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 tumours 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.

View this trial on ClinicalTrials.gov

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