Using Kadcyla and Neratinib to Treat Early HER2-positive Breast Cancer with Residual Disease

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This Phase 2 study focuses on patients with resected Stage I-III HER2-positive breast cancer who have detectable molecular residual disease after standard neoadjuvant therapy. Participants will receive neratinib in addition to their standard T-DM1 adjuvant therapy, with neratinib administered orally for up to 12 months. The study consists of two stages, with the first stage enrolling up to 8 participants to assess the clearance of minimal residual disease, followed by a second stage enrolling up to 5 participants. The goal is to evaluate whether the addition of neratinib improves outcomes for this specific patient population.

Why it matters

Who can join: the full rules

Inclusion Criteria:

1. 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.
2. Receiving adjuvant T-DM1, with evidence of MRD (positive test by Inivata RaDaR) after receiving 2-6 cycles of T-DM1
3. No contraindications to T-DM1 or neratinib
4. No clinical or radiographic evidence of recurrent or metastatic disease
5. Previous Therapy requirements:

   * Received 2-6 cycles of trastuzumab-DM1 in the adjuvant setting
   * 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
6. ECOG performance status 0-1.
7. Patient must have adequate organ function
8. WOCBP must have a negative serum \[beta\] HCG test result.
9. WOCBP must agree to use highly effective contraception
10. Male participants must agree to use highly effective contraception
11. 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.
12. Signed informed consent

Exclusion Criteria:

1. Prior therapy with any HER2 tyrosine kinase inhibitor
2. Clinical or radiographic evidence of suspected or confirmed metastatic disease.
3. Previous or concurrent malignancy within 3 years of study entry, with exceptions
4. Impaired cardiovascular function or clinically significant cardiovascular diseases
5. Known positive serology for HIV that is not currently controlled with anti-retroviral therapy,
6. 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.
7. Impaired gastrointestinal function or disease that may significantly alter the absorption of neratinib
8. 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.

Where it's running

• University Health Network: Princess Margaret Cancer Centre
  Toronto, Ontario, Canada Recruiting

Study contacts

• Study coordinator: David Cescon, MD PhD
• Email: Dave.cescon@uhn.ca
• Phone: 416-946-2245

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.