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

Study Overview
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Brief Summary
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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
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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

Official Title
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Circulating Tumor Cells and Adjuvant Treatment De-escalation After Neoadjuvant Therapy With Trastuzumab and Pertuzumab for HER2 Positive Early Breast Cancer

Conditions
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Breast Neoplasms, HER2-positive Breast Cancer, Circulating Tumor Cell

Intervention / Treatment
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* Drug: Pertuzumab
* Drug: Trastuzumab
* Other: Circulating tumor cells


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Interventional Model Description: Patients will be divided into 2 cohorts, based on HER2 positivity in CTCs at baseline of neoadjuvant therapy. Cohort 1: HER2 positive CTCs: randomization to adjuvant trastuzumab versus trastuzumab + pertuzumab in patients with pathological complete response Cohort 2: HER2 negative/absent CTCs: randomization to adjuvant trastuzumab versus trastuzumab + pertuzumab in patients with pathological complete response
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cohort 1, Arm A - trastuzumab<br>Adjuvant trastuzumab for patients with HER2 positive CTCs at baseline | Drug: Trastuzumab<br>* 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<br>* Other names: Zedora;Other: Circulating tumor cells<br>* Blood sample collection for examination of CTCs at baseline of neoadjuvant therapy. Tests for HER2 positivity will be done.<br>* Other names: CTCs;|
| Experimental: Cohort 1, Arm B - Trastuzumab + pertuzumab<br>Adjuvant trastuzumab + pertuzumab for patients with HER2 positive CTCs at baseline | Drug: Pertuzumab<br>* Adjuvant trastuzumab + pertuzumab (arm B of the 2 cohorts: 1: HER2 positive CTCs at baseline and 2: HER2 negative/absent CTCs at baseline)<br>* Other names: Perjeta;Drug: Trastuzumab<br>* 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<br>* Other names: Zedora;Other: Circulating tumor cells<br>* Blood sample collection for examination of CTCs at baseline of neoadjuvant therapy. Tests for HER2 positivity will be done.<br>* Other names: CTCs;|
| Active Comparator: Cohort 2, Arm A - trastuzumab<br>Adjuvant trastuzumab for patients with HER2 negative/absent CTCs at baseline | Drug: Trastuzumab<br>* 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<br>* Other names: Zedora;Other: Circulating tumor cells<br>* Blood sample collection for examination of CTCs at baseline of neoadjuvant therapy. Tests for HER2 positivity will be done.<br>* Other names: CTCs;|
| Experimental: Cohort 2, Arm B - Trastuzumab + pertuzumab<br>Adjuvant trastuzumab + pertuzumab for patients with HER2 negative/absent CTCs at baseline | Drug: Pertuzumab<br>* Adjuvant trastuzumab + pertuzumab (arm B of the 2 cohorts: 1: HER2 positive CTCs at baseline and 2: HER2 negative/absent CTCs at baseline)<br>* Other names: Perjeta;Drug: Trastuzumab<br>* 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<br>* Other names: Zedora;Other: Circulating tumor cells<br>* Blood sample collection for examination of CTCs at baseline of neoadjuvant therapy. Tests for HER2 positivity will be done.<br>* Other names: CTCs;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HER2 therapy disease-free survival | To compare the disease-free survival between trastuzumab and trastuzumab + pertuzumab arms | 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 | From adjuvant therapy initiation to recurrence or death by any cause, whichever came first, assessed up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prognostic factors for disease-free survival |  | 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 | At baseline | 
| Adverse events | To compare the adverse events between trastuzumab and trastuzumab + pertuzumab | Adjuvant period (1 year) |