Breast Neoplasms, Circulating Tumor Cell, HER2-positive Breast Cancer
Conditions
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
Interventions
DRUGPertuzumab
Adjuvant trastuzumab + pertuzumab (arm B of the 2 cohorts: 1: HER2 positive CTCs at baseline and 2: HER2 negative/absent CTCs at baseline)
DRUGTrastuzumab
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
OTHERCirculating tumor cells
Blood sample collection for examination of CTCs at baseline of neoadjuvant therapy. Tests for HER2 positivity will be done.
Sponsors
AC Camargo Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention 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
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Prognostic factors for disease-free survival | At baseline and adjuvant therapy (18 months) | — |
| 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 |
| Adverse events | Adjuvant period (1 year) | To compare the adverse events between trastuzumab and trastuzumab + pertuzumab |
Countries
Brazil
Contacts
Primary ContactMarcelle G Cesca, MD
Backup ContactLudmilla TD Chinen, PhD
Outcome results
None listed