Clinical Trial: Neoadjuvant Therapy in TRIPle Negative Breast Cancer With antiPDL1

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Neo-Adjuvant Study With the PDL1-directed Antibody in Triple Negative Locally Advanced Breast Cancer Undergoing Treatment With Nab-paclitaxel and Carboplatin

Brief Summary: This study that aims to evaluate the addition of MPDL3280A (atezolizumab) to carboplatin and nab-paclitaxel in patients with locally advanced triple negative breast cancer. compared to the control arm of carboplatin and abraxane. Half of participants will receive MPDL3280A in combination with carboplatin and abraxane, while the other half will receive only carboplatin and abraxane.

Detailed Summary:

Emerging evidence shows that many breast cancers with triple negative and basal like features have infiltration by mononuclear cells and lymphocytes. Irrespective of the entity of tumor infiltration by mononuclear cells, expression of immune regulatory checkpoints such as PD-1 and its ligand B7-H1 (or PD-L1) negatively affect the results of treatments. These data suggest that a subset of patients have an ongoing immune response within the tumor micro-environment, and that PD-L1 expression is an adaptive method of tumor resistance to tumor infiltrating lymphocytes, which in turn are needed for response to chemotherapy. Overall, the data suggests a role for immune regulation of response to chemotherapy, and support the concept that blockade of immune check-points may favor the achievement of durable response by immune mechanisms themselves, and in combination with classical chemotherapy.

MPDL3280A (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 B7.1. Based on these considerations, we plan to conduct a study of the combination of abraxane and carboplatin with or without PDL1-directed antibody in women with locally advanced breast cancer suitable for neoadjuvant therapy with the aim to improve event-free survival


Sponsor: Fondazione Michelangelo

Current Primary Outcome: Event Free Survival (EFS) [ Time Frame: 5 years after the randomization of the last patient ]

To compare EFS (disease progression while on neoadjuvant therapy or disease recurrence after surgery) in the two study arms


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Pathological complete response (pCR) [ Time Frame: At surgery, an expected average of 34 weeks after the randomization of the last patient ]
    Assess the rate of pCR defined as ypT0-ypTis ypN0 at surgery in the two treatment arms
  • Clinical objective response [ Time Frame: Participants will be followed for the duration of neoadjuvant therapy, an expected average of 26 weeks ]
    Assess the clinical response rate after neoadjuvant therapy
  • Distant Event Free Survival (DEFS) [ Time Frame: 5 years after the randomization of the last patients ]
    To compare the DEFS, defined as the occurrence of distant disease progression while on neoadjuvant therapy or distant recurrence after surgery in the two treatment arms
  • Number of participants with adverse events as a Measure of Safety and Tolerability [ Time Frame: Participants wil be followed for up to 5 years from the last randomized patient ]
    Number of participants with Adverse Events and related grade


Original Secondary Outcome: Same as current

Information By: Fondazione Michelangelo

Dates:
Date Received: November 3, 2015
Date Started: April 2016
Date Completion: October 2022
Last Updated: July 12, 2016
Last Verified: July 2016