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

Phase 2RecruitingNCT04993014

AC Camargo Cancer Center80 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Breast Neoplasms HER2-positive Breast Cancer

Interventions

PertuzumabDRUG

Adjuvant trastuzumab + pertuzumab (arm B of the 2 cohorts: 1: HER2 positive CTCs at baseline and 2: HER2 negative/absent CTCs at baseline)

TrastuzumabDRUG

Adjuvant trastuzumab (arm A of the 2 cohorts: 1: HER2 positive CTCs at baseline and 2: HER2 negative/absent CTCs at baseline) Association with pertuzumab in arm B of the 2 cohorts

Circulating tumor cellsOTHER

Blood sample collection for examination of CTCs at baseline of neoadjuvant therapy. Tests for HER2 positivity will be done.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

HER2 therapy disease-free survival

To compare the disease-free survival between trastuzumab and trastuzumab + pertuzumab arms

Time frame: From adjuvant therapy initiation to recurrence or death by any cause, whichever came first, assessed up to 5 years

CTCs disease-free survival

To compare the disease-free survival between patients with HER2 positive CTCs at baseline versus HER2 negative/absent CTCs

Time frame: From adjuvant therapy initiation to recurrence or death by any cause, whichever came first, assessed up to 5 years

Secondary Outcomes

Prognostic factors for disease-free survival

Time frame: At baseline and adjuvant therapy (18 months)

Correlation of CTCs and pathological complete response

To evaluate if there is a correlation of HER2 positivity and the number of CTCs/ml and the pathological response

Time frame: At baseline

Adverse events

To compare the adverse events between trastuzumab and trastuzumab + pertuzumab

Time frame: Adjuvant period (1 year)