Circulating Tumor Cells and Treatment De-escalation After Neoadjuvant Therapy for HER2 Positive Breast Cancer

Phase 2

Recruiting

• Conditions: Circulating Tumor Cell; Breast Neoplasms; HER2-positive Breast Cancer
• Interventions: Drug: Pertuzumab; Other: Circulating tumor cells; Drug: Trastuzumab

• Registration Number: NCT04993014
• Lead Sponsor: AC Camargo Cancer Center

Brief Summary

Phase II unicentric randomized trial which will include early HER2 positive breast cancer patients, candidate to neoadjuvant therapy with trastuzumab and pertuzumab. Circulating tumor cells will be collected at neoadjuvant therapy baseline.

Patients with pathological complete response will be randomized in 1:1 ratio for adjuvant trastuzumab (arm A) versus trastuzumab + pertuzumab (arm B) in a two factorial design: group A, with HER2 positive CTCs and group B, with HER2 negative/absent CTCs.

Detailed Description

Patients with HER2 positive breast cancer (hormone receptors positive or negative), which are candidate to neoadjuvant therapy with pertuzumab and trastuzumab will be included.

Blood samples will be collected at baseline (before neoadjuvant start) for the analysis of CTCs and its positivity for HER2 by IHC and ISH.

Patients with pathological complete response will be included in the randomization phase of the study. There will be 2 cohorts: HER2 positive CTCs at baseline and HER2 negative/absent CTCs at baseline. In each cohort, patients will be randomized in 1:1 ratio for adjuvant trastuzumab versus adjuvant trastuzumab + pertuzumab

Study Timeline

• Study Start: 2021-03-01
• Status Verified: 2021-07
• Study First Submitted: 2021-07-21
• Study First Submitted QC: 2021-07-28
• Last Update Submitted: 2021-07-28
• Study First Posted: 2021-08-06
• Last Update Posted: 2021-08-06
• Primary Completion: 2024-04-30
• Study Completion: 2028-04-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

• HER2 positive breast cancer (hormone receptors positive or negative)
• Stage I to III
• Indication for neoadjuvant therapy with chemo (any regimen) + trastuzumab + pertuzumab
• Breast surgery after neoadjuvant therapy
• Preserved coagnition
• ECOG 0-3
• For the randomization phase: pathological complete response (ypT0/ypTis and ypN0)
• Agreement on participation and signature of de ICF

Exclusion Criteria

• Contradindication for trastuzumab or pertuzumab
• Adjuvant chemotherapy. Hormone therapy is allowed
• Second primary tumor < 5 years, with an exception for treated non-melanoma skin cancer, and in situ cervical cancer

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Cohort 1, Arm A - trastuzumab	Circulating tumor cells	Adjuvant trastuzumab for patients with HER2 positive CTCs at baseline
Cohort 1, Arm B - Trastuzumab + pertuzumab	Circulating tumor cells	Adjuvant trastuzumab + pertuzumab for patients with HER2 positive CTCs at baseline
Cohort 2, Arm A - trastuzumab	Circulating tumor cells	Adjuvant trastuzumab for patients with HER2 negative/absent CTCs at baseline
Cohort 2, Arm B - Trastuzumab + pertuzumab	Circulating tumor cells	Adjuvant trastuzumab + pertuzumab for patients with HER2 negative/absent CTCs at baseline
Cohort 1, Arm B - Trastuzumab + pertuzumab	Trastuzumab	Adjuvant trastuzumab + pertuzumab for patients with HER2 positive CTCs at baseline
Cohort 1, Arm A - trastuzumab	Trastuzumab	Adjuvant trastuzumab for patients with HER2 positive CTCs at baseline
Cohort 1, Arm B - Trastuzumab + pertuzumab	Pertuzumab	Adjuvant trastuzumab + pertuzumab for patients with HER2 positive CTCs at baseline
Cohort 2, Arm A - trastuzumab	Trastuzumab	Adjuvant trastuzumab for patients with HER2 negative/absent CTCs at baseline
Cohort 2, Arm B - Trastuzumab + pertuzumab	Pertuzumab	Adjuvant trastuzumab + pertuzumab for patients with HER2 negative/absent CTCs at baseline
Cohort 2, Arm B - Trastuzumab + pertuzumab	Trastuzumab	Adjuvant trastuzumab + pertuzumab for patients with HER2 negative/absent CTCs at baseline

Primary Outcome Measures

Name	Time	Method
HER2 therapy disease-free survival	From adjuvant therapy initiation to recurrence or death by any cause, whichever came first, assessed up to 5 years	To compare the disease-free survival between trastuzumab and trastuzumab + pertuzumab arms
CTCs disease-free survival	From adjuvant therapy initiation to recurrence or death by any cause, whichever came first, assessed up to 5 years	To compare the disease-free survival between patients with HER2 positive CTCs at baseline versus HER2 negative/absent CTCs

Secondary Outcome Measures

Name	Time	Method
Correlation of CTCs and pathological complete response	At baseline	To evaluate if there is a correlation of HER2 positivity and the number of CTCs/ml and the pathological response
Prognostic factors for disease-free survival	At baseline and adjuvant therapy (18 months)
Adverse events	Adjuvant period (1 year)	To compare the adverse events between trastuzumab and trastuzumab + pertuzumab

Trial Locations

Locations (1)

A.C. Camargo Cancer Center; 🇧🇷 São Paulo, Brazil