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Neoadjuvant Therapy in TRIPle Negative Breast Cancer With antiPDL1 (NeoTRIPaPDL1)

This study is currently recruiting participants.
See Contacts and Locations
Verified July 2016 by Fondazione Michelangelo
Sponsor:
Information provided by (Responsible Party):
Fondazione Michelangelo
ClinicalTrials.gov Identifier:
NCT02620280
First received: November 3, 2015
Last updated: July 12, 2016
Last verified: July 2016
  Purpose
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.

Condition Intervention Phase
Invasive Ductal Breast Carcinoma Drug: Carboplatin Drug: Abraxane Drug: MPDL3280A Procedure: Surgery Drug: Anthra Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Neo-Adjuvant Study With the PDL1-directed Antibody in Triple Negative Locally Advanced Breast Cancer Undergoing Treatment With Nab-paclitaxel and Carboplatin

Resource links provided by NLM:


Further study details as provided by Fondazione Michelangelo:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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


Estimated Enrollment: 272
Study Start Date: April 2016
Estimated Study Completion Date: October 2022
Estimated Primary Completion Date: May 2022 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Carbo-abrax, surgery, anthra
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
Carboplatin AUC 2 will be given i.v. on day 1 and day 8 q 3 weeks for a total of 8 cycles
Other Name: Carboplatin Teva
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
Other Name: nab-paclitaxel
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
Experimental: Carbo-abrax-MPDL3280A, surgery, anthra
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
Carboplatin AUC 2 will be given i.v. on day 1 and day 8 q 3 weeks for a total of 8 cycles
Other Name: Carboplatin Teva
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
Other Name: nab-paclitaxel
Drug: MPDL3280A
MPDL3280A, 1200 mg. will be given i.v. infusion on day 1 q 3 weeks for a total of 8 cycles
Other Name: Atezolizumab
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

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

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Female patients aged 18 years or older with locally advanced or inflammatory breast cancers
  2. Histologically confirmed unilateral breast cancer with invasive ductal histology not otherwise specified (NOS) of high proliferation or grade
  3. HER2 negative disease
  4. Negative estrogen receptor (ER) and progesterone receptor (PgR), both < 1% locally assessed
  5. 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
  6. ECOG performance status 0 or 1
  7. 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
  8. Willing and able to comply with the protocol
  9. Consent to the collection of blood samples
  10. 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.

Exclusion Criteria:

  1. Evidence of bilateral breast cancer or metastatic disease (M1)
  2. Cases with an histology different from invasive ductal NOS of high proliferation or grade
  3. Patients with HER2-positive disease according to ASCO/CAP guidelines 2013
  4. 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
  5. Previous treatment with chemotherapy, hormonal therapy or an investigational drug for any type of malignancy
  6. Previous investigational treatment for any condition within 4 weeks of randomization date
  7. 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
  8. 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
  9. Pre-existing motor or sensory neuropathy of grade > 1 for any reason
  10. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  11. Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the MPDL3280A formulation
  12. Patients with prior allogeneic stem cell or solid organ transplantation
  13. 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
  14. History of idiopathic pulmonary fibrosis (including bronchiolitis obliterans with organizing pneumonia) or evidence of active pneumonitis on screening chest computed tomography scan
  15. Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, fatty liver, and inherited liver disease
  16. History of HIV infection, active hepatitis B (chronic or acute), or hepatitis C infection. Patients with past or resolved hepatitis B infection (defined as having a negative HBsAg test and a positive hepatitis B core antigen [anti-HBc] test) are eligible.

Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction assay (PCR) is negative for HCV RNA 17. Active tuberculosis 18. Severe infections within 4 weeks prior to cycle 1 Day 1, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia. Signs or symptoms of significant infection within 2 weeks prior to cycle 1 Day 1 19. Received oral or IV antibiotics within 2 weeks prior to Cycle 1 Day 1 20. Other serious illness or medical condition including: history of documented congestive cardiac failure; New York Heart Association (NYHA) Class II or greater CHF; angina pectoris requiring anti-anginal medication or unstable angina within 6 months prior to cycle 1 Day 1; evidence of transmural infarction on ECG; myocardial infarction stroke or transient ischemic attack (TIA) within 6 months prior to cycle 1 Day 1; poorly controlled hypertension (e.g. systolic >180 mm Hg or diastolic >100 mm Hg; however, patients with hypertension which is well controlled on medication are eligible); clinically significant valvular heart disease; high-risk uncontrolled arrhythmias 21. Patients with a history of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant and precluding informed consent or adversely affecting compliance with study drugs 22. Serious uncontrolled infections (bacterial or viral) or poorly controlled diabetes mellitus 23. Abnormal baseline hematological values 24. Abnormal baseline laboratory tests for serum total bilirubin, liver function tests, alkaline phosphatase, serum creatinine, INR and aPTT 25. Baseline left ventricular ejection fraction (LVEF) < 50% by echocardiography or multi-gated scintigraphic scan (MUGA) 26. Major surgical procedure within 28 days prior to cycle 1 Day 1 or anticipation of need for a major surgical procedure during the course of the study 27. Influenza vaccination should be given during influenza season only (approximately October to March). Patients must not receive live, attenuated influenza vaccine (e.g., FluMist®) within 4 weeks prior to cycle 1 Day 1 or at any time during the study.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02620280

Contacts
Contact: Pinuccia Valagussa +39 02 870864 ext 22 pinuccia.valagussa@fondazionemichelangelo.org
Contact: Elisa Coradeschi +39 02 870864 ext 23 elisa.coradeschi@fondazionemichelangelo.org

Locations
Austria
Brustgesundheitzentrum Tirol, Univ. Frauenklinik Innsbruck Recruiting
Innsbruck, Austria, 6020
Principal Investigator: Daniel Egle, MD         
Universitätsklinik für Innere Medizin III, mit Hämatologie, internistischer Onkologie, Hämostaseologie, Infektiologie, Rheumatologie und Onkologisches Zentrum Not yet recruiting
Salzburg, Austria, 5020
Principal Investigator: Richard Greil, MD         
Germany
Klinikum Augsburg International Patient Service Not yet recruiting
Augsburg, Germany, 86156
Principal Investigator: Arthur Wischnik, MD         
Frauenarzt-Zentrum-Zehlendorf Not yet recruiting
Berlin, Germany, 14169
Principal Investigator: Gerd Graffunder, MD         
Augusta-Kranken-Anstalt gGmbH Klinik für Hämatologie, Onkologie & Palliativmedizin Not yet recruiting
Bochum, Germany, 447891
Principal Investigator: Dirk Beheringer, MD         
Bethanien-Krankenhaus Onkologisches Zentrum Not yet recruiting
Frankfurt, Germany, 60389
Principal Investigator: Hans Tesch, MD         
Markus Krankenhaus Klinik für Gynäkologie und Geburtshilfe Recruiting
Frankfurt, Germany, 60431
Principal Investigator: Marc Thill, MD         
Gynäkologisch-Onkologische Praxis Not yet recruiting
Hannover, Germany, 30177
Principal Investigator: Hans-Joachim Lück, MD         
Uniklinik Köln Klinik und Poliklinic für Frauenheilkunde und Geburtshilfe Brestzentrum Not yet recruiting
Köln, Germany, 50931
Principal Investigator: Stefan Krämer, MD         
Brustzentrum St. Elisabeth-Krankenhaus Recruiting
Köln, Germany, 50935
Principal Investigator: Claudia Schumaker, MD         
Interdisciplinary Oncology Center (IOZ) Not yet recruiting
Munchen, Germany, 80336
Principal Investigator: Wolfang Eiermann, MD         
Praxis Gynäkologie Arabella Not yet recruiting
Munchen, Germany, 81925
Principal Investigator: Anita Prechtl, MD         
Italy
AOU Arcispedale Sant'Anna - Cona - Ferrara Not yet recruiting
Ferrara, Italy, 44124
Principal Investigator: Antonio Frassoldati, MD         
Istituto Toscano Tumori Ospedale Misericordia Not yet recruiting
Grosseto, Italy, 58100
Principal Investigator: Carmelo Bengala, MD         
Ospedale San Raffaele Recruiting
Milano, Italy, 20132
Principal Investigator: Luca Gianni, MD         
Fondazione IRCCS Istituto nazionale dei Tumori Recruiting
Milano, Italy, 20133
Principal Investigator: Mariani Gabriella, MD         
Istituto Europeo di Oncologia Recruiting
Milano, Italy, 20141
Principal Investigator: Marco Colleoni, MD         
Arcispedale Santa Maria Nuova - A.O. Reggio Emilia Recruiting
Reggio Emilia, Italy, 42123
Principal Investigator: Giancarlo Bisagni, MD         
Spain
Hospital Universitario 12 de octubre Not yet recruiting
Madrid, Spain, 28041
Principal Investigator: Eva Maria Ciruleos Gil, MD         
Hospital Universitario HM Sanchinarro, Centro Integral Oncologico Clara Campal (CIOCC) Not yet recruiting
Madrid, Spain, 28050
Principal Investigator: Isabel Calvo Plaza, MD         
Hospital Clinico Universitario de Valencia Servicio de Onco-Hematologia Not yet recruiting
Valencia, Spain, 46010
Principal Investigator: Begoña Bermejo, MD         
Hospital Miguel Servet Recruiting
Zaragoza, Spain, 59009
Principal Investigator: Anton Antòn-Torres, MD         
Sponsors and Collaborators
Fondazione Michelangelo
Investigators
Study Chair: Luca Gianni, MD Ospedale San Raffaele
  More Information

Responsible Party: Fondazione Michelangelo
ClinicalTrials.gov Identifier: NCT02620280     History of Changes
Other Study ID Numbers: FM-14-B02
2014-005017-23 ( EudraCT Number )
Study First Received: November 3, 2015
Last Updated: July 12, 2016

Keywords provided by Fondazione Michelangelo:
Triple Negative Breast Cancer

Additional relevant MeSH terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Carcinoma, Ductal, Breast
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Carcinoma, Ductal
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Ductal, Lobular, and Medullary
Paclitaxel
Carboplatin
Albumin-Bound Paclitaxel
Antibodies, Monoclonal
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 21, 2017