Kadcyla And Neratinib for Interception of HER2+ Breast Cancer With Molecular Residual Disease
Primary Purpose
Breast Cancer, HER2-positive Breast Cancer
Status
Recruiting
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Neratinib
Sponsored by
About this trial
This is an interventional treatment trial for Breast Cancer
Eligibility Criteria
Inclusion Criteria:
- 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
- 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
Exclusion Criteria:
- 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.
Sites / Locations
- University Health Network: Princess Margaret Cancer CentreRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Neratinib Arm
Arm Description
Standard T-DM1 (3.6mg/kg) IV infusion every 3 weeks administered with Neratinib (160 mg) orally once daily up to 1 year.
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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
Toxicities of the combination of neratinib and trastuzumab-DM1 in the study population measured by CTCAE 5.0
Characterize dynamic changes and kinetics in ctDNA MRD+ for enrolled patients measured by ctDNA MRD Detection by RaDaR assay
Full Information
NCT ID
NCT05388149
First Posted
May 18, 2022
Last Updated
July 30, 2023
Sponsor
University Health Network, Toronto
1. Study Identification
Unique Protocol Identification Number
NCT05388149
Brief Title
Kadcyla And Neratinib for Interception of HER2+ Breast Cancer With Molecular Residual Disease
Official Title
Kadcyla And Neratinib for Interception of HER2+ Breast Cancer With Molecular Residual Disease
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 6, 2022 (Actual)
Primary Completion Date
July 2025 (Anticipated)
Study Completion Date
July 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Health Network, Toronto
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief 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. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer, HER2-positive Breast Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Neratinib Arm
Arm Type
Experimental
Arm Description
Standard T-DM1 (3.6mg/kg) IV infusion every 3 weeks administered with Neratinib (160 mg) orally once daily up to 1 year.
Intervention Type
Drug
Intervention Name(s)
Neratinib
Other Intervention Name(s)
NERLYNX
Intervention Description
Neratinib administered as 40mg tablets
Primary Outcome Measure Information:
Title
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
Time Frame
At week 12
Secondary Outcome Measure Information:
Title
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
Time Frame
Up to 3 years
Title
Toxicities of the combination of neratinib and trastuzumab-DM1 in the study population measured by CTCAE 5.0
Time Frame
Up to 3 years
Title
Characterize dynamic changes and kinetics in ctDNA MRD+ for enrolled patients measured by ctDNA MRD Detection by RaDaR assay
Time Frame
Up to 3 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
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
Exclusion Criteria:
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
David Cescon, MD PhD
Phone
416-946-2245
Email
Dave.cescon@uhn.ca
Facility Information:
Facility Name
University Health Network: Princess Margaret Cancer Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1Z5
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dave Cescon, M.D.
Phone
416-946-2245
Email
dave.cescon@uhn.ca
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Kadcyla And Neratinib for Interception of HER2+ Breast Cancer With Molecular Residual Disease
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