Phase 2
Completed N=612
A Study of Tucatinib vs. Placebo in Combination With Capecitabine & Trastuzumab in Patients With Advanced HER2+ Breast Cancer
Source: ClinicalTrials.gov NCT02614794 ↗Enrolled (actual)
612
Serious AEs
31.0%
Results posted
Sep 2020
Primary outcomePrimary: Progression-free Survival (PFS) Per RECIST 1.1 as Determined by Blinded Independent Central Review (BICR) — 7.8; 5.6 months
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Progression-free Survival (PFS) Per RECIST 1.1 as Determined by Blinded Independent Central Review (BICR) |
7.8; 5.6 | — |
| SECONDARY PFS in Patients With Brain Metastases at Baseline Using RECIST 1.1 as Determined by BICR |
7.6; 5.4 | — |
| SECONDARY Overall Survival (OS) at Time of Primary Analysis |
21.9; 17.4 | — |
| SECONDARY Confirmed Objective Response Rate (ORR) Per RECIST 1.1 as Determined by BICR |
40.7; 23.4 | — |
| SECONDARY ORR Per RECIST 1.1 as Determined by Investigator Assessment |
41.4; 23.0 | — |
| SECONDARY PFS Per RECIST 1.1 as Determined by Investigator Assessment at Time of Primary Analysis |
7.5; 4.3 | — |
| SECONDARY Duration of Response (DOR) Per RECIST 1.1 as Determined by BICR |
8.3; 6.3 | — |
| SECONDARY DOR Per RECIST 1.1 as Determined by Investigator Assessment |
7.0; 6.9 | — |
| SECONDARY Clinical Benefit Rate (CBR) as Determined by BICR Per RECIST 1.1 |
59.8; 38.1 | — |
| SECONDARY CBR Per RECIST 1.1 as Determined by Investigator Assessment |
58.0; 37.6 | — |
| SECONDARY Incidence of Adverse Events (AEs) at Time of Primary Analysis |
401; 191; 223; 96; 104; 53 | — |
| SECONDARY Frequency of Dose Modifications |
220; 81; 216; 80; 84; 21 | — |
| SECONDARY Incidence of Health Resources Utilization |
143; 75; 124; 64; 10; 6 | — |
| SECONDARY Pharmacokinetic Measure: Ctrough of Tucatinib |
246.1; 227.6; 507.1; 253.2; 257.6; 247.8 | — |
| SECONDARY Pharmacokinetic Measure: ONT-993 |
25.5; 22.6; 47.7; 25.2; 24.5; 20.9 | — |
| SECONDARY Overall Survival (OS) at Time of Final Analysis |
24.7; 19.2 | — |
| SECONDARY PFS Per RECIST 1.1 as Determined by Investigator Assessment at Time of Final Analysis |
7.6; 4.9 | — |
| SECONDARY Incidence of Adverse Events (AEs) at Time of Final Analysis |
401; 191; 248; 101; 123; 58 | — |
| SECONDARY Frequency of Dose Modifications at Time of Final Analysis |
237; 85; 232; 84; 92; 21 | — |
Eligibility Criteria
Double-blind Phase Inclusion Criteria
- Histologically confirmed HER2+ breast carcinoma, with HER2+ defined by in situ hybridization (ISH), immunohistochemistry (IHC), or fluorescence in situ hybridization (FISH) methodology
- Received previous treatment with trastuzumab, pertuzumab, and T-DM1
- Progression of unresectable locally advanced or metastatic breast cancer after last systemic therapy (as confirmed by investigator), or be intolerant of last systemic therapy
- Have measurable or non-measurable disease assessable by RECIST 1.1
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- Adequate hepatic and renal function and hematologic parameters
- Left ventricular ejection fraction (LVEF) ≥ 50%
- CNS Inclusion - Based on screening brain magnetic resonance imaging (MRI), patients must have one of the following:
- No evidence of brain metastases
- Untreated brain metastases not needing immediate local therapy
- Previously treated brain metastases not needing immediate local therapy
- Brain metastases previously treated with local therapy may either be stable since treatment or may have progressed since prior local CNS therapy
- Patients treated with CNS local therapy for newly identified lesions found on contrast brain MRI performed during screening for this study may be eligible to enroll if the following criteria are met:
i. Time since whole brain radiation therapy (WBRT) is ≥ 21 days prior to first dose of study treatment, time since stereotactic radiosurgery (SRS) is ≥ 7 days prior to first dose of study treatment, or time since surgical resection is ≥ 28 days.
ii. Other sites of disease assessable by RECIST 1.1 are present
- Relevant records of any CNS treatment must be available to allow for classification of target and non-target lesions
Double-blind Phase Exclusion Criteria
- Previously been treated with:
- lapatinib within 12 months of starting study treatment (except in cases where lapatinib was given for ≤ 21 days and was discontinued for reasons other than disease progression or toxicity)
- neratinib, afatinib, or other investigational HER2/epidermal growth factor receptor (EGFR) or HER2 tyrosine kinase inhibitor (TKI) at any time previously
- capecitabine (or other fluoropyrimidine) for metastatic disease except in cases where capecitabine was given for 2.0 cm in size, unless approved by medical monitor
- Ongoing use of systemic corticosteroids for control of symptoms of brain metastases at a total daily dose of > 2 mg of dexamethasone (or equivalent)
- Any brain lesion thought to require immediate local therapy. Patients who undergo local treatment for such lesions identified by screening contrast brain MRI may still be eligible for the study based on criteria described under CNS inclusion criteria
- Known or suspected leptomeningeal disease (LMD)
- Poorly controlled seizures Unblinded Phase Crossover Inclusion Criteria - Participants who were randomized to the control arm (placebo + trastuzumab + capecitabine) must meet the following criteria to be eligible to crossover to the experimental arm.
- Have measurable or non-measurable disease assessable by RECIST 1.1
- For patients who were randomized to the control arm and on the long-term follow-up period at the time of crossover screening: have progression of unresectable locally advanced or metastatic breast cancer after last systemic therapy (as confirmed by investigator), or be intolerant of last systemic therapy.
- Have an ECOG Performance Status of 0 or 1
- Have a life expectancy of at least 6 months
- Have adequate hepatic and renal function and hematologic parameters
- Left ventricular ejection fraction (LVEF) ≥ 50%
- CNS Inclusion - Based on screening brain magnetic resonance imaging (MRI), patients must have one of the following:
i. No evidence of brain metastases ii. Untreated brain metastases not needing immediate local therapy iii. Previously treated brain metastases not needing immediate local therapy
- Bra
Data sourced from ClinicalTrials.gov (NCT02614794). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.