Neoadjuvant Therapy in TRIPle Negative Breast Cancer With antiPDL1

NCT02620280 | Completed Phase 3 DMC

• 2 other identifiers: FM-14-B022014-005017-23
• Study Type: interventional
• Target: 278
• Locations: 7 countries
• Sites: 41

Brief 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.

Conditions

Invasive Ductal Breast Carcinoma

Keywords

Triple Negative Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Event Free Survival (EFS)

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

  5 years after the randomization of the last patient

Secondary Outcomes (4)

• Pathological complete response (pCR)

  At surgery, an expected average of 34 weeks after the randomization of the last patient

• Clinical objective response

  Participants will be followed for the duration of neoadjuvant therapy, an expected average of 26 weeks

• Distant Event Free Survival (DEFS)

  5 years after the randomization of the last patients

• Number of participants with adverse events as a Measure of Safety and Tolerability

  Participants wil be followed for up to 5 years from the last randomized patient

Study Arms (2)

Carbo-abrax, surgery, anthra

ACTIVE COMPARATOR

Patients will receive a combination of carboplatin and abraxane as neoadjuvant treatment. Definite surgery will be performed not later than 6 weeks after the last dose of neoadjuvant therapy. Four cycles of AC or EC or FEC will then be delivered as adjuvant chemotherapy

Drug: Carboplatin; Drug: Abraxane; Procedure: Surgery; Drug: Anthra

Carbo-abrax-MPDL3280A, surgery, anthra

EXPERIMENTAL

Patients will receive a combination of carboplatin, abraxane and MPDL3280A as neoadjuvant treatment. Definite surgery will be performed not later than 6 weeks after the last dose of neoadjuvant therapy. Four cycles of AC or EC or FEC will then be delivered as adjuvant chemotherapy

Drug: Carboplatin; Drug: Abraxane; Drug: MPDL3280A; Procedure: Surgery; Drug: Anthra

Interventions

Carboplatin DRUG

Carboplatin AUC 2 will be given i.v. on day 1 and day 8 q 3 weeks for a total of 8 cycles

Also known as: Carboplatin Teva

Carbo-abrax, surgery, anthra; Carbo-abrax-MPDL3280A, surgery, anthra

Abraxane DRUG

Abraxane, 125 mg/m2 will be given i.v. on day 1 and day 8 q 3 weeks for a total of 8 cycles

Also known as: nab-paclitaxel

Carbo-abrax, surgery, anthra; Carbo-abrax-MPDL3280A, surgery, anthra

MPDL3280A DRUG

MPDL3280A, 1200 mg. will be given i.v. infusion on day 1 q 3 weeks for a total of 8 cycles

Also known as: Atezolizumab

Carbo-abrax-MPDL3280A, surgery, anthra

Surgery PROCEDURE

Breast cancer surgery (breast and axilla) either conservative or radical not later than 6 weeks

Carbo-abrax, surgery, anthra; Carbo-abrax-MPDL3280A, surgery, anthra

Anthra DRUG

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

Carbo-abrax, surgery, anthra; Carbo-abrax-MPDL3280A, surgery, anthra

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female patients aged 18 years or older with early high-risk and locally advanced or inflammatory breast cancers
• Histologically confirmed unilateral breast cancer with invasive ductal histology not otherwise specified (NOS) of high proliferation or grade
• HER2 negative disease
• Negative estrogen receptor (ER) and progesterone receptor (PgR), both \< 1% locally assessed
• Representative paraffin-embedded (FFPE) tumor block taken at diagnostic biopsy for confirmation of HER2, ER and PgR eligibility, for assessment of PDL-1 expression and for further exploratory biomarker evaluation is mandatory
• ECOG performance status 0 or 1
• Written informed consent to participate in the trial (approved by the Institutional Review Board \[IRB\]/ Independent Ethics Committee \[IEC\]) obtained prior to any study specific screening procedures
• Willing and able to comply with the protocol
• Consent to the collection of blood samples
• For women who are not postmenopausal (≥ 12 months of non-therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or use single or combined contraceptive methods that result in a failure rate of \< 1% per year during the treatment period and for at least 90 days after the last dose of study drug.

You may not qualify if:

• Evidence of bilateral breast cancer or metastatic disease (M1)
• Cases with an histology different from invasive ductal NOS of high proliferation or grade
• Patients with HER2-positive disease according to ASCO/CAP guidelines 2013
• Pregnant or lactating women. Documentation of a negative pregnancy test must be available for premenopausal women with intact reproductive organs and for women less than one year after the last menstrual cycle
• Previous treatment with chemotherapy, hormonal therapy or an investigational drug for any type of malignancy
• Previous investigational treatment for any condition within 4 weeks of randomization date
• Administration of a live, attenuated vaccine within 4 weeks before cycle 1 Day 1 or anticipation that such a live attenuated vaccine will be required during the study
• Previous or concomitant invasive malignancy of any other type or previous invasive breast cancer. Patients with curatively treated basal cell carcinoma of the skin or in situ cervix cancer are generally eligible
• Pre-existing motor or sensory neuropathy of grade \> 1 for any reason
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
• Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the MPDL3280A formulation
• Patients with prior allogeneic stem cell or solid organ transplantation
• History of autoimmune disease including, but not limited to, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
• History of idiopathic pulmonary fibrosis (including bronchiolitis obliterans with organizing pneumonia) or evidence of active pneumonitis on screening chest computed tomography scan
• Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, fatty liver, and inherited liver disease

Sponsors & Collaborators

• Fondazione Michelangelo: lead

Study Sites (41)

Brustgesundheitzentrum Tirol, Univ. Frauenklinik Innsbruck

Innsbruck, 6020, Austria

Location

Universitätsklinik für Innere Medizin III, mit Hämatologie, internistischer Onkologie, Hämostaseologie, Infektiologie, Rheumatologie und Onkologisches Zentrum

Salzburg, 5020, Austria

Location

Klinikum Augsburg International Patient Service

Augsburg, 86156, Germany

Location

Frauenarzt-Zentrum-Zehlendorf

Berlin, 14169, Germany

Location

Augusta-Kranken-Anstalt gGmbH Klinik für Hämatologie, Onkologie & Palliativmedizin

Bochum, 447891, Germany

Location

Uniklinik Köln Klinik und Poliklinic für Frauenheilkunde und Geburtshilfe Brestzentrum

Cologne, 50931, Germany

Location

Brustzentrum St. Elisabeth-Krankenhaus

Cologne, 50935, Germany

Location

Bethanien-Krankenhaus Onkologisches Zentrum

Frankfurt, 60389, Germany

Location

Markus Krankenhaus Klinik für Gynäkologie und Geburtshilfe

Frankfurt, 60431, Germany

Location

Gynäkologisch-Onkologische Praxis

Hanover, 30177, Germany

Location

NCT Nationales Centrum für Tumorerkrankungen

Heidelberg, 69120, Germany

Location

Interdisciplinary Oncology Center (IOZ)

München, 80336, Germany

Location

Cork University Hospital

Cork, Ireland

Location

Beaumont Hospital

Dublin, Ireland

Location

Mater Misericordiae University Hospital

Dublin, Ireland

Location

St. James's Hospital

Dublin, Ireland

Location

University Hospital Waterford

Waterford, Ireland

Location

Policlinico S. Orsola Malpoghi

Bologna, 40138, Italy

Location

Istituto per la Ricerca sul Cancro

Candiolo, 10060, Italy

Location

IST San Martino

Genova, 16132, Italy

Location

Istituto Toscano Tumori Ospedale Misericordia

Grosseto, 58100, Italy

Location

Ospedale San Raffaele

Milan, 20132, Italy

Location

Fondazione IRCCS Istituto nazionale dei Tumori

Milan, 20133, Italy

Location

Istituto Europeo di Oncologia

Milan, 20141, Italy

Location

Ospedale Luigi Sacco

Milan, 20160, Italy

Location

Arcispedale Santa Maria Nuova - A.O. Reggio Emilia

Reggio Emilia, 42123, Italy

Location

Ospedale Santa Maria della Misericordia

Udine, 33100, Italy

Location

Russian Cancer Research Center named after N.N.Blokhin

Moscow, Russia

Location

Petrov Research Institute of Oncology, Department of Breast Cancer

Saint Petersburg, Russia

Location

Road clinical hospital of OJSC "Russian Railways

Saint Petersburg, Russia

Location

Hospital Duran i Reynal Institut Català d'Oncologia

L'Hospitalet de Llobregat, 08908, Spain

Location

Hospital Clínico San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario 12 de octubre

Madrid, 28041, Spain

Location

Hospital Universitario HM Sanchinarro, Centro Integral Oncologico Clara Campal (CIOCC)

Madrid, 28050, Spain

Location

Hospital Clinico Universitario de Valencia Servicio de Onco-Hematologia

Valencia, 46010, Spain

Location

Hospital Miguel Servet

Zaragoza, 59009, Spain

Location

C. Christian Hospital Taiwan

Changhua, Taiwan

Location

Kaohsiung Medical University Hospital

Kaohsiung City, Taiwan

Location

China Medical University Hospital No.2

Taichung, Taiwan

Location

National Taiwan University Hospital

Taipei, Taiwan

Location

Veteran General Hospital Taipei

Taipei, Taiwan

Location

Related Publications (2)

• Gianni L, Huang CS, Egle D, Bermejo B, Zamagni C, Thill M, Anton A, Zambelli S, Bianchini G, Russo S, Ciruelos EM, Greil R, Semiglazov V, Colleoni M, Kelly C, Mariani G, Del Mastro L, Maffeis I, Valagussa P, Viale G. Pathologic complete response (pCR) to neoadjuvant treatment with or without atezolizumab in triple-negative, early high-risk and locally advanced breast cancer: NeoTRIP Michelangelo randomized study. Ann Oncol. 2022 May;33(5):534-543. doi: 10.1016/j.annonc.2022.02.004. Epub 2022 Feb 17.

  PMID: 35182721 DERIVED

• Perez-Garcia J, Soberino J, Racca F, Gion M, Stradella A, Cortes J. Atezolizumab in the treatment of metastatic triple-negative breast cancer. Expert Opin Biol Ther. 2020 Sep;20(9):981-989. doi: 10.1080/14712598.2020.1769063. Epub 2020 May 25.

  PMID: 32450725 DERIVED

MeSH Terms

Conditions

Carcinoma, Ductal, Breast; Triple Negative Breast Neoplasms

Interventions

Carboplatin; Albumin-Bound Paclitaxel; 130-nm albumin-bound paclitaxel; atezolizumab; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Carcinoma, Ductal; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Ductal, Lobular, and Medullary; Breast Neoplasms; Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Luca Gianni, MD

  Ospedale San Raffaele

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2015
• First Posted: December 2, 2015
• Study Start: April 1, 2016
• Primary Completion: January 1, 2024
• Study Completion: January 7, 2024
• Last Updated: March 6, 2024

Record last verified: 2024-03

Locations

AU (2); RU (3); TW (5); DE (10); IE (5); IT (10); ES (6)