Safety of Continuing HER-2 Directed Therapy in Overt Left Ventricular Dysfunction: A Randomized, Controlled Trial
Overview
- Phase
- Phase 2
- Intervention
- Trastuzumab
- Conditions
- Breast Cancer
- Sponsor
- Population Health Research Institute
- Enrollment
- 130
- Locations
- 8
- Primary Endpoint
- primary efficacy outcome
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
Trastuzumab is an important treatment for HER 2 positive breast cancer. But trastuzumab can cause injury to the heart, and this is one of the main reasons it cannot be administered as planned. Heart injury can often be successfully treated using cardiac medications. The objectives of SCHOLAR-2 are to evaluate whether is it safe and effective to continue trastuzumab, pertuzumab or trastuzumab-emtansine (T-DM1) in patients with early stage HER-2 positive breast cancer despite mild, minimally symptomatic or asymptomatic systolic left ventricular dysfunction as compared with a guideline-driven approach of withholding or discontinuing trastuzumab, pertuzumab or trastuzumab-emtansine (T-DM1).
In SCHOLAR-2, we will compare two thresholds of withholding or discontinuing trastuzumab/pertuzumab/trastuzumab-emtansine: a threshold that is currently advocated for by existing treatment practice guidelines versus a more aggressive threshold that allows trastuzumab/pertuzumab/trastuzumab-emtansine to continue at lower levels of LVEF than currently supported by guideline documents.
Detailed Description
SCHOLAR-2 is a Phase II open-label randomized controlled trial with blinded outcome event ascertainment with a target sample size of 130. Control Group Recommendations for continuing or holding trastuzumab, pertuzumab, or trastuzumab-emtansine (T-DM1) for the control group are guided by an adaptation of the 2008 Canadian recommendations. Intervention Group The intervention group will continue to receive trastuzumab, pertuzumab, or trastuzumab-emtansine (T-DM1) in the setting of asymptomatic decline in LVEF up to an LVEF of 40% as outlined in the criteria listed in Table 3. For reasons of practicality, in the intervention group, the first dose of trastuzumab, pertuzumab, or trastuzumab-emtansine (T-DM1) after randomization can be administered up to 3 weeks late. This will allow time for the participant to be reviewed by a cardiologist and to receive ACE-I/angiotensin receptor blocker and/or beta-blocker, and for dose titration. Study assessments will occur: 1. 3 weeks after randomization 2. 6 weeks after randomization 3. Follow-up at every 3 months thereafter until 12 months after the last dose of trastuzumab, pertuzumab, or trastuzumab-emtansine (T-DM1)
Investigators
Eligibility Criteria
Inclusion Criteria
- •Stage I-III HER-2 positive breast cancer
- •Receiving adjuvant or neoadjuvant therapy with trastuzumab, pertuzumab, or trastuzumab-emtansine (T-DM1)
- •Evidence of left ventricular dysfunction, as defined by at least one of:
- •a) LVEF \< 54% or b) LVEF ≥54% and either i) fall in LVEF of ≥15% from prior to trastuzumab, pertuzumab, or trastuzumab-emtansine (T-DM1) exposure, or ii) New York Heart Association (NYHA) class II heart failure symptoms within the past 6 months
Exclusion Criteria
- •Current use of both angiotensin converting enzyme inhibitor (ACEI) /angiotensin receptor blocker (ARB) and beta-blocker
- •Contra-indication to both ACE-I/ARB and beta-blockers
- •NYHA class III or IV heart failure
- •Systolic blood pressure \<100mmHg
- •Current or planned pregnancy or breastfeeding
Arms & Interventions
Control Group
Recommendations for continuing or holding trastuzumab, pertuzumab, or trastuzumab-emtansine (T-DM1) for the control group are guided by an adaptation of the 2008 Canadian recommendations.
Intervention: Trastuzumab
Control Group
Recommendations for continuing or holding trastuzumab, pertuzumab, or trastuzumab-emtansine (T-DM1) for the control group are guided by an adaptation of the 2008 Canadian recommendations.
Intervention: Pertuzumab
Control Group
Recommendations for continuing or holding trastuzumab, pertuzumab, or trastuzumab-emtansine (T-DM1) for the control group are guided by an adaptation of the 2008 Canadian recommendations.
Intervention: Trastuzumab emtansine
Intervention Group
The intervention group will continue to receive trastuzumab, pertuzumab, or trastuzumab-emtansine (T-DM1) in the setting of asymptomatic decline in LVEF up to an LVEF of 40% as outlined in the criteria listed in Table 3. For reasons of practicality, in the intervention group, the first dose of trastuzumab, pertuzumab, or trastuzumab-emtansine (T-DM1) after randomization can be administered up to 3 weeks late. This will allow time for the participant to be reviewed by a cardiologist and to receive ACE-I/angiotensin receptor blocker and/or beta-blocker, and for dose titration.
Intervention: Trastuzumab
Intervention Group
The intervention group will continue to receive trastuzumab, pertuzumab, or trastuzumab-emtansine (T-DM1) in the setting of asymptomatic decline in LVEF up to an LVEF of 40% as outlined in the criteria listed in Table 3. For reasons of practicality, in the intervention group, the first dose of trastuzumab, pertuzumab, or trastuzumab-emtansine (T-DM1) after randomization can be administered up to 3 weeks late. This will allow time for the participant to be reviewed by a cardiologist and to receive ACE-I/angiotensin receptor blocker and/or beta-blocker, and for dose titration.
Intervention: Pertuzumab
Intervention Group
The intervention group will continue to receive trastuzumab, pertuzumab, or trastuzumab-emtansine (T-DM1) in the setting of asymptomatic decline in LVEF up to an LVEF of 40% as outlined in the criteria listed in Table 3. For reasons of practicality, in the intervention group, the first dose of trastuzumab, pertuzumab, or trastuzumab-emtansine (T-DM1) after randomization can be administered up to 3 weeks late. This will allow time for the participant to be reviewed by a cardiologist and to receive ACE-I/angiotensin receptor blocker and/or beta-blocker, and for dose titration.
Intervention: Trastuzumab emtansine
Outcomes
Primary Outcomes
primary efficacy outcome
Time Frame: one year
the proportion of participants completing trastuzumab, pertuzumab, or trastuzumab-emtansine (T-DM1) as planned at its initiation
co-primary safety outcomes
Time Frame: one year
1. LVEF at the close-out visit, and 2. The composite of NYHA class III or IV heart failure or cardiovascular death.
Secondary Outcomes
- secondary outcome measures the composite of NYHA class III or IV heart failure, breast cancer relapse, or all-cause mortality.(one year)