Ignite Creation Date:
2024-05-06 @ 11:46 AM
Last Modification Date:
2024-10-26 @ 12:49 PM
Study NCT ID:
NCT03595592
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-03-06
First Post:
2018-07-11
Brief Title:
Neoadjuvant Treatment of HER2 Positive Early High-risk and Locally Advanced Breast Cancer
Sponsor:
Fondazione Michelangelo
Organization:
Fondazione Michelangelo
Study Overview
Official Title:
Atezolizumab Pertuzumab and Trastuzumab With Chemotherapy as Neoadjuvant Treatment of HER2 Positive Early High-risk and Locally Advanced Breast Cancer APTneo
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
APTneo
Brief Summary:
n the present study the neoadjuvant approach with the anti-HER2 trastuzumab and pertuzumab combined with carboplatin and paclitaxel will be used to compare the Event-Free Survival EFS in regimens with and without atezolizumab Following the neoadjuvant part of the study after surgery all patients will continue to receive trastuzumab and pertuzumab to complete one year of anti-HER2 therapy Similarly patients allocated to receive atezolizumab will continue atezolizumab to complete one year In addition several IHC and molecular assays will be performed before and during the period of chemotherapy administration and at surgery with the goal of defining a marker of efficacy to be later validated in a larger adjuvant setting
Detailed Description:
Dual targeting of HER2 with trastuzumab and pertuzumab in HER2-positive breast cancer is linked to clinical evidence of reversal of initial resistance to trastuzumab Baselga J et al J Clin Oncol 2010 in cases progressing on trastuzumab therapy and in dramatic improvement in progression free and overall survival when the two monoclonal antibodies are used in combination with docetaxel THP regimen as first line therapy of metastatic disease as shown in the CLEOPATRA study Swain S et al ESMO abstract 2014 The randomized NeoSphere study showed that the same THP regimen given for 4 cycles as neoadjuvant treatment increased the rate of pathologic complete response pCR over that with conventional docetaxel and trastuzumab or docetaxel and pertuzumab Gianni L et al Lancet Oncol 2012
Encouraging clinical data emerging in the field of tumor immunotherapy have demonstrated that therapies focused on enhancing T cell responses against cancer can result in a significant survival benefit in patients with advanced malignancies Hodi FS and Dranoff G J Cutan Pathol 2010 Kantoff PW et al New Engl J Med 2010 Chen DS et al Clin Cancer Res 2012 Many human tumors have been found to overexpress PD L1 which acts to suppress anti tumor immunity PD 1 is an inhibitory receptor expressed on T cells following T cell activation which is sustained in states of chronic stimulation such as in chronic infection or canc Atezolizumab is a human monoclonal antibody containing an engineered Fc-domain to optimize efficacy and safety that targets PD-L1 and blocks binding of its receptors including PD-1 and B71
In addition to being involved in the natural progression of cancer immunity can affect the activity of various anticancer agents Accordingly recent evidence suggests that some chemotherapeutic drugs such as anthracyclines and oxaliplatin rely on the induction of anticancer immune responses Immune responses also play a major role in the efficacy of targeted therapies with monoclonal antibodies Stagg J et al Breast Care 2012 Studies have shown monoclonal antibodies such as trastuzumab and rituximab rely in part on immunemediated killing through antibody-dependent cellular cytotoxicity ADCC While innate immune responses appear to be important for tumor antigen-targeted monoclonal antibody therapies recent studies in mice and correlative clinical evidence suggest that trastuzumab may also stimulate adaptive antitumor immunity These studies raise the possibility that combination strategies may be used to capitalize on the adaptive tumor-specific immunity generated by anti-HER2 monoclonal antibodies
Based on these considerations we plan to conduct a randomized neoadjuvant study of the combination of trastuzumab pertuzumab carboplatin and paclitaxel with or without atezolizumab in women with early high-risk and locally advanced HER2-positive suitable for neoadjuvant therapy One study arm will also include anthracycline and cyclophosphamide
Encouraging clinical data emerging in the field of tumor immunotherapy have demonstrated that therapies focused on enhancing T cell responses against cancer can result in a significant survival benefit in patients with advanced malignancies Hodi FS and Dranoff G J Cutan Pathol 2010 Kantoff PW et al New Engl J Med 2010 Chen DS et al Clin Cancer Res 2012 Many human tumors have been found to overexpress PD L1 which acts to suppress anti tumor immunity PD 1 is an inhibitory receptor expressed on T cells following T cell activation which is sustained in states of chronic stimulation such as in chronic infection or canc Atezolizumab is a human monoclonal antibody containing an engineered Fc-domain to optimize efficacy and safety that targets PD-L1 and blocks binding of its receptors including PD-1 and B71
In addition to being involved in the natural progression of cancer immunity can affect the activity of various anticancer agents Accordingly recent evidence suggests that some chemotherapeutic drugs such as anthracyclines and oxaliplatin rely on the induction of anticancer immune responses Immune responses also play a major role in the efficacy of targeted therapies with monoclonal antibodies Stagg J et al Breast Care 2012 Studies have shown monoclonal antibodies such as trastuzumab and rituximab rely in part on immunemediated killing through antibody-dependent cellular cytotoxicity ADCC While innate immune responses appear to be important for tumor antigen-targeted monoclonal antibody therapies recent studies in mice and correlative clinical evidence suggest that trastuzumab may also stimulate adaptive antitumor immunity These studies raise the possibility that combination strategies may be used to capitalize on the adaptive tumor-specific immunity generated by anti-HER2 monoclonal antibodies
Based on these considerations we plan to conduct a randomized neoadjuvant study of the combination of trastuzumab pertuzumab carboplatin and paclitaxel with or without atezolizumab in women with early high-risk and locally advanced HER2-positive suitable for neoadjuvant therapy One study arm will also include anthracycline and cyclophosphamide
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2017-000981-31 | EUDRACT_NUMBER | None | None |