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Invasive Ductal Breast CarcinomaPhase 3NeoTRIPaPDL1NCT02620280

Neoadjuvant Therapy in TRIPle Negative Breast Cancer With antiPDL1

A Phase 3 study testing Carboplatin, Abraxane and MPDL3280A in people with Invasive Ductal Breast Carcinoma, run by Fondazione Michelangelo at 41 sites in 7 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Invasive Ductal Breast Carcinoma
What is being tested?
Carboplatin, Abraxane and MPDL3280A
Could I receive a placebo?
No, everyone receives an active treatment
How many people
278 participants
Where
41 sitesin 7 countries
Study dates
Apr 2016to 7 Jan 2024
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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.

Who cannot join

  • 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
Show all 18Show fewer
  • 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
  • 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.
  • -

Trial locations and contacts

41 sites in 7 countries.

41 sites in 7 countries

Germany10 sites

  • Klinikum Augsburg International Patient Service

    Augsburg, 86156

  • Frauenarzt-Zentrum-Zehlendorf

    Berlin, 14169

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

    Bochum, 447891

  • Uniklinik Köln Klinik und Poliklinic für Frauenheilkunde und Geburtshilfe Brestzentrum

    Cologne, 50931

  • Brustzentrum St. Elisabeth-Krankenhaus

    Cologne, 50935

  • Bethanien-Krankenhaus Onkologisches Zentrum

    Frankfurt, 60389

  • Markus Krankenhaus Klinik für Gynäkologie und Geburtshilfe

    Frankfurt, 60431

  • Gynäkologisch-Onkologische Praxis

    Hanover, 30177

  • NCT Nationales Centrum für Tumorerkrankungen

    Heidelberg, 69120

  • Interdisciplinary Oncology Center (IOZ)

    München, 80336

Other trials in Germany

Italy10 sites

  • Policlinico S. Orsola Malpoghi

    Bologna, 40138

  • Istituto per la Ricerca sul Cancro

    Candiolo, 10060

  • IST San Martino

    Genova, 16132

  • Istituto Toscano Tumori Ospedale Misericordia

    Grosseto, 58100

  • Ospedale San Raffaele

    Milan, 20132

  • Fondazione IRCCS Istituto nazionale dei Tumori

    Milan, 20133

  • Istituto Europeo di Oncologia

    Milan, 20141

  • Ospedale Luigi Sacco

    Milan, 20160

  • Arcispedale Santa Maria Nuova - A.O. Reggio Emilia

    Reggio Emilia, 42123

  • Ospedale Santa Maria della Misericordia

    Udine, 33100

Other trials in Italy

Spain6 sites

  • Hospital Duran i Reynal Institut Català d'Oncologia

    L'Hospitalet de Llobregat, 08908

  • Hospital Clínico San Carlos

    Madrid, 28040

  • Hospital Universitario 12 de octubre

    Madrid, 28041

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

    Madrid, 28050

  • Hospital Clinico Universitario de Valencia Servicio de Onco-Hematologia

    Valencia, 46010

  • Hospital Miguel Servet

    Zaragoza, 59009

Other trials in Spain

Ireland5 sites

  • Cork University Hospital

    Cork

  • Beaumont Hospital

    Dublin

  • Mater Misericordiae University Hospital

    Dublin

  • St. James's Hospital

    Dublin

  • University Hospital Waterford

    Waterford

Other trials in Ireland

Taiwan5 sites

  • C. Christian Hospital Taiwan

    Changhua

  • Kaohsiung Medical University Hospital

    Kaohsiung City

  • China Medical University Hospital No.2

    Taichung

  • National Taiwan University Hospital

    Taipei

  • Veteran General Hospital Taipei

    Taipei

Other trials in Taiwan

Russia3 sites

  • Russian Cancer Research Center named after N.N.Blokhin

    Moscow

  • Petrov Research Institute of Oncology, Department of Breast Cancer

    Saint Petersburg

  • Road clinical hospital of OJSC "Russian Railways

    Saint Petersburg

Other trials in Russia

Austria2 sites

  • Brustgesundheitzentrum Tirol, Univ. Frauenklinik Innsbruck

    Innsbruck, 6020

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

    Salzburg, 5020

Other trials in Austria

About this study

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

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.

Read the 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

Being tested
Carboplatin, Abraxane, MPDL3280A, Surgery, Anthra
Keywords
Triple Negative Breast Cancer
Medical subject headings
Carcinoma, Ductal, Breast, Triple Negative Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CarboplatinDrug

    Also called Carboplatin Teva

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

  • AbraxaneDrug

    Also called nab-paclitaxel

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

  • MPDL3280ADrug

    Also called Atezolizumab

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

  • SurgeryProcedure or surgery

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

  • AnthraDrug

    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

Study groups in NCT02620280
Study groupRoleWhat they receive
Carbo-abrax, surgery, anthraActive comparatorPatients 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
Receives: Drug: Carboplatin; Drug: Abraxane; Procedure: Surgery; Drug: Anthra
Carbo-abrax-MPDL3280A, surgery, anthraExperimentalPatients 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
Receives: Drug: Carboplatin; Drug: Abraxane; Drug: MPDL3280A; Procedure: Surgery; Drug: Anthra

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Event Free Survival (EFS)

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

    Measured: 5 years after the randomization of the last patient

Secondary outcomes (4)

  1. Pathological complete response (pCR)

    Assess the rate of pCR defined as ypT0-ypTis ypN0 at surgery in the two treatment arms

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

  2. Clinical objective response

    Assess the clinical response rate after neoadjuvant therapy

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

  3. Distant Event Free Survival (DEFS)

    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

    Measured: 5 years after the randomization of the last patients

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

    Number of participants with Adverse Events and related grade

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Dec 2015 (estimated)
  2. Study startApr 2016
  3. Primary completionJan 2024
  4. Study completion7 Jan 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
278 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02620280
Sponsor's protocol ID
FM-14-B02
Other IDs
2014-005017-23, 2014
Acronym
NeoTRIPaPDL1
Status last verified
Mar 2024
First submitted
3 Nov 2015
Last updated
6 Mar 2024
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 35182721

  • 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.

    PubMed 32450725

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Carboplatin, Abraxane and MPDL3280A in people with Invasive Ductal Breast Carcinoma, run by Fondazione Michelangelo at 41 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 41 sites in Germany, Italy, Spain, Ireland, Taiwan and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Event Free Survival (EFS) (time frame: 5 years after the randomization of the last patient). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02620280, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Mar 2024.

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