NCT02620280

Neoadjuvant Therapy in TRIPle Negative Breast Cancer With antiPDL1

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

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 278 (actual)
• Sponsor: Fondazione Michelangelo · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study that aims to evaluate the addition of MPDL3280A (atezolizumab) to carboplatin and nab-paclitaxel in patients with early high-risk and 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 description

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

Conditions

• Invasive Ductal Breast Carcinoma

Interventions

Type	Name	Description
DRUG	Carboplatin	Carboplatin AUC 2 will be given i.v. on day 1 and day 8 q 3 weeks for a total of 8 cycles
DRUG	Abraxane	Abraxane, 125 mg/m2 will be given i.v. on day 1 and day 8 q 3 weeks for a total of 8 cycles
DRUG	MPDL3280A	MPDL3280A, 1200 mg. will be given i.v. infusion on day 1 q 3 weeks for a total of 8 cycles
PROCEDURE	Surgery	Breast cancer surgery (breast and axilla) either conservative or radical not later than 6 weeks
DRUG	Anthra	AC or EC (adriamycin or epirubicin and cyclophosphamide) or FEC (fluorouracil, epirubicin, and cyclophosphamide) on day 1 every three weeks for 4 cycles to be delivered after surgery

Timeline

• Start date: 2016-04-01
• Primary completion: 2024-01-01
• Completion: 2024-01-07
• First posted: 2015-12-02
• Last updated: 2024-03-06

Locations

41 sites across 7 countries: Austria, Germany, Ireland, Italy, Russia, Spain, Taiwan