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. Patients in this study will be randomly assigned to get either tucatinib or placebo (a pill with no medicine). This is a blinded study, so neither patients nor their doctors will know whether a patient gets tucatinib or placebo. Each treatment cycle lasts 21 days. Patients will swallow tucatinib pills or placebo 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 based on blinded independent central review (BICR)
Secondary Outcome:
  • Progression-free survival (PFS) in patients with baseline brain metastases per RECIST 1.1 based on BICR
  • Overall Survival (OS)
  • PFS per RECIST 1.1 based on investigator assessment
  • Objective response rate (ORR) per RECIST 1.1 based on BICR
  • Duration of response (DOR) per RECIST 1.1 based on BICR
  • Clinical benefit rate (CBR)
  • Incidence of adverse events (AEs)
  • Incidence of health resources utilization
  • Quality of life as measured by EQ-5D-5L questionnaire
  • Pharmacokinetic (PK) measure: Ctrough
This is a randomized, international, multi-centre, double-blinded study in patients with progressive unresectable locally advanced or metastatic HER2+ breast cancer who have had prior treatment with trastuzumab, pertuzumab and T-DM1. Patients will be randomized in a 2:1 ratio to receive tucatinib or placebo in combination with capecitabine and trastuzumab. 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). No crossover from placebo to tucatinib will be allowed. 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. Contrast brain MRI will be performed at baseline in all patients. Efficacy assessments (CT of chest, abdomen and pelvis at a minimum) utilize RECIST 1.1 and include patients with evaluable tumours defined as measurable target lesions and non-measurable non-target lesions. RECIST assessment is performed at baseline, every 6 weeks for the first 24 weeks, and then every 9 weeks thereafter. Repeat MRI of the brain will be required on this same schedule only in those patients with brain metastases identified at baseline. All treatment decisions are made based upon investigator assessment. All patients undergo a repeat MRI of the brain within 30 days of the end of treatment unless previously performed at time of disease progression. Patients in both arms of the study will be followed for OS after completion of study treatment.

View this trial on ClinicalTrials.gov

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Canadian Cancer Society

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