Breast CancerPhase 2NCT05388149
Kadcyla And Neratinib for Interception of HER2+ Breast Cancer With Molecular Residual Disease
A Phase 2 study testing Neratinib in people with Breast Cancer and HER2-positive Breast Cancer, run by University Health Network, Toronto at 1 site in Canada.
Trial summary
This is a Phase 2 study for patients with resected Stage I-III HER2+ breast cancer with detected molecular residual disease (MRD+) following standard neoadjuvant and locoregional therapy delivered with curative intent. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer, HER2-positive Breast Cancer
- What is being tested?
- Neratinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteCanada
- Study dates
- 6 Dec 2022to Jul 2027
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female patients ≥ 18 years of age with histologically confirmed, resected HER2 positive stage I-III breast cancer, with residual invasive disease following prior neoadjuvant trastuzumab (+/- pertuzumab)-based chemotherapy.
- Receiving adjuvant T-DM1, with evidence of MRD (positive test by Inivata RaDaR) after receiving 2-6 cycles of T-DM1
- No contraindications to T-DM1 or neratinib
- No clinical or radiographic evidence of recurrent or metastatic disease
- Previous Therapy requirements:
- Received 2-6 cycles of trastuzumab-DM1 in the adjuvant setting
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- Received min of 12 weeks of endocrine therapy (ER+ patients)
- Adjuvant radiation permitted (minimum 14-day washout required)
- No prior neratinib or other HER2 tyrosine kinase inhibitor
- ECOG performance status 0-1.
- Patient must have adequate organ function
- WOCBP must have a negative serum [beta] HCG test result.
- WOCBP must agree to use highly effective contraception
- Male participants must agree to use highly effective contraception
- Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
- Signed informed consent
Who cannot join
- Prior therapy with any HER2 tyrosine kinase inhibitor
- Clinical or radiographic evidence of suspected or confirmed metastatic disease.
- Previous or concurrent malignancy within 3 years of study entry, with exceptions
- Impaired cardiovascular function or clinically significant cardiovascular diseases
- Known positive serology for HIV that is not currently controlled with anti-retroviral therapy,
- Has a known history of or is positive for active hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (defined as HCV RNA [qualitative] is detected). HBV DNA must be undetectable and HBsAg negative at Screening Visit. Participants who have had definitive treatment for HCV are permitted if HCV RNA is undetectable at Screening Visit.
- Impaired gastrointestinal function or disease that may significantly alter the absorption of neratinib
- Medical, psychiatric, cognitive, or other conditions that may compromise the patient's ability to understand the patient information, give informed consent, comply with the study protocol, or complete the study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
University Health Network: Princess Margaret Cancer Centre
Toronto, Ontario, M5G 1Z5
Dave Cescon, M.D., 416-946-2245, dave.cescon@uhn.ca
About this study
This is a Phase 2 study for patients with resected Stage I-III HER2+ breast cancer with detected molecular residual disease (MRD+) following standard neoadjuvant and locoregional therapy delivered with curative intent. In this study Patients will be treated with neratinib in addition to their standard T-DM1 adjuvant therapy. Neratinib will be administered orally at a dose of 160 mg daily for up to 12 months, or until the time of clinical recurrence, discontinuation due to toxicity, or withdrawal of consent. This study will have two stages, stage 1 would enroll up to 8 participants to clear the Minimal Residual Disease (MRD) and Stage 2 will enroll up to 5 participants. The purpose of this study is to determine if this study population would have a better outcome from adding neratinib to their standard T-DM1 adjuvant therapy.
- Conditions
- Breast Cancer, HER2-positive Breast Cancer
- Being tested
- Neratinib
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NeratinibDrug
Also called NERLYNX
Neratinib administered as 40mg tablets
| Study group | Role | What they receive |
|---|---|---|
| Neratinib Arm | Experimental | Standard T-DM1 (3.6mg/kg) IV infusion every 3 weeks administered with Neratinib (160 mg) orally once daily up to 1 year. Receives: Drug: Neratinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clearance of ctDNA with the addition of neratinib to trastuzumab-DM1 in patients with MRD detectable by the RaDaR assay, following standard neoadjuvant therapy, surgery, and initiation of T-DM1
Measured: At week 12
Secondary outcomes (3)
Clinical outcomes for MRD+ patients treated with escalated strategy, including invasive breast cancer-free survival (IBCFS) measured by Invasive Breast Cancer-Free Survival and Distant Metastasis Free Survival
Measured: Up to 3 years
Toxicities of the combination of neratinib and trastuzumab-DM1 in the study population measured by CTCAE 5.0
Measured: Up to 3 years
Characterize dynamic changes and kinetics in ctDNA MRD+ for enrolled patients measured by ctDNA MRD Detection by RaDaR assay
Measured: Up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2022
- Study start6 Dec 2022
- Primary completionJul 2027 (estimated)
- Study completionJul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05388149
- Sponsor's protocol ID
- 22-5307
- Other IDs
- KAN-HER2 MRD
- Status last verified
- Oct 2026
- First submitted
- 18 May 2022
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No