Adjuvant Treatment for High-risk Triple Negative Breast Cancer Patients With the Anti-PD-l1 Antibody Avelumab

NCT02926196 | Completed Phase 3

• 2 other identifiers: A-BRAVE-Trial2016-000189-45
• Study Type: interventional
• Target: 474
• Locations: 2 countries
• Sites: 70

Brief Summary

Phase III randomized trial of the anti-PD-L1 antibody avelumab as adjuvant or post-neoadjuvant treatment for high-risk triple negative breast cancer patients. The overall protocol-defined patient population will include the following two strata of patients:

• Stratum A - Patients who have completed treatment with curative intent including surgery of the primary tumor followed by adjuvant chemotherapy .
• Stratum B - Patients who have completed treatment with curative intent including neoadjuvant chemotherapy followed by surgery of the primary tumor and (if indicated) further adjuvant chemotherapy.

Conditions

Triple Negative Breast Neoplasms

Keywords

ER-Negative; PR-Negative; HER2-Negative

Outcome Measures

Primary Outcomes (2)

• Disease free survival

  DFS is defined as the time from randomization to locoregional invasive recurrence, second primary invasive breast cancer, other second primary cancer (excluding in-situ cancers), distant metastasis or death from any cause.

  Up to 5 years after randomization

• Disease free survival in PD-L1-positive patients

  DFS is defined as the time from randomization to locoregional invasive recurrence, second primary invasive breast cancer, other second primary cancer (excluding in-situ cancers), distant metastasis or death from any cause.

  Up to 5 years after randomization

Secondary Outcomes (2)

• Overall survival

  Up to 5 years after randomization

• Safety profile

  From Baseline up to 5 years after randomization

Study Arms (2)

Arm Avelumab

EXPERIMENTAL

Avelumab 10 mg/kg I.V. q2w for 1 year (52 weeks)

Drug: MSB0010718C

Arm Observation

NO INTERVENTION

Observation as per guidelines

Interventions

MSB0010718C DRUG

MSB0010718C-Avelumab is formulated as vials of 200 mg strength for IV administration

Also known as: Avelumab

Arm Avelumab

Eligibility Criteria

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

You may qualify if:

• Male or female subjects aged \> 18 years
• Signed written informed consent before any trial-related procedure is undertaken that is not part of the standard patient management
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Patients must have completed treatment with curative intent including: surgery and adjuvant chemotherapy.
• Patients must have completed adjuvant chemotherapy including at least 3 courses of an anthracycline agent and 3 courses of a taxane agent. Patients who received dose-dense regimens and those who received carboplatin as part of the adjuvant treatment are eligible.
• No more than 10 weeks may elapse between the completion of last adjuvant treatment (adjuvant chemotherapy or surgery) and randomization.
• \. Normal organ and marrow function
• White blood count (WBC) greater than or equal to 2.5 x109/L
• Absolute neutrophil count (ANC) greater than or equal to 1.5 x109/L
• Absolute lymphocyte count greater or equal to 0.5 x109/L
• Platelet count greater than or equal to 100 x109/L
• Hemoglobin greater than or equal to 9 g/dL
• Serum creatinine less or equal to 1.5 x the upper limit of laboratory normal range (ULN)
• Adequate hepatic function defined by a total bilirubin level less or equal to 1.5 x ULN range and AST and ALT levels less or equal than 2.5 x ULN for all subjects. For patients with known Gilbert's syndrome, total bilirubin levels less or equal than 2 x ULN range (with direct bilirubin less than ULN) will be accepted.
• \. Highly effective contraception (i.e. methods with a failure rate of less than 1 % per year) for both male and female subjects if the risk of conception exists (Note: The effects of the trial treatment on the developing human fetus are unknown; thus, women of childbearing potential and men must agree to use highly effective contraception, defined in Appendix A or as stipulated in national or local guidelines. Highly effective contraception must be used 28 days prior to first trial treatment administration, for the duration of trial treatment, and at least for 60 days after stopping trial treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this trial, the treating physician should be informed immediately).

You may not qualify if:

• Stage IV breast cancer.
• History of any prior (ipsi- and/or contralateral) invasive breast carcinoma diagnosed within 10 years.
• Synchronous bilateral breast cancer, unless both tumors confirmed as triple negative disease.
• History of non-breast malignancies within the 5 years prior to study entry, except for the following: Carcinoma in situ (CIS) of the cervix, CIS of the colon, Basal cell and squamous cell carcinomas of the skin.
• Prior organ transplantation, including allogeneic stem-cell transplantation.
• Prior or concomitant treatment with any other investigational agents.
• Prior therapy with any antibody / drug targeting T-cell coregulatory proteins (immune-checkpoints) such as PD-1, PD-L1, or cytotoxic T-lymphocyte antigen-4 (CTLA-4).
• Concurrent anticancer treatment (for example, cytoreductive therapy, immune therapy, or cytokine therapy except for erythropoietin)
• Major surgery for any reason, within 4 weeks of randomization and / or if the subject has not fully recovered from the surgery within 4 weeks of randomization.
• Concomitant treatment with all herbal (alternative) remedies with immunostimulating properties (for example, mistletoe extract) or known to potentially interfere with major organ function (for example, hypericin).
• Subjects receiving immunosuppressive agents (such as steroids) for any reason should be tapered off these drugs before initiation of the trial treatment (with the exception of subjects with adrenal insufficiency, who may continue corticosteroids at physiologic replacement dose, equivalent to ≤ 10 mg prednisone daily).
• Significant acute or chronic infections including, among others:
• Known history of testing positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome.
• Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive).
• Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent:

Sponsors & Collaborators

• Istituto Oncologico Veneto IRCCS: lead
• University of Padova: collaborator
• Dipartimento di scienze chirurgiche, Oncologiche e Gastroenterologiche: collaborator

Study Sites (70)

Ospedale di Bergamo

Bergamo, BG, Italy

Location

Policlinico Sant'Orsola Malpighi

Bologna, BO, 40138, Italy

Location

Ospedale di Bellaria

Bologna, BO, Italy

Location

Azienda Sanitaria Locale Brindisi

Brindisi, BR, Italy

Location

Azienda Spedali Civili di Brescia

Brescia, BS, Italy

Location

A.S.O. S.Croce e Carle di Cuneo

Cuneo, CN, 12100, Italy

Location

AOU Policlinico "Vittorio. Emanuele

Catania, CT, Italy

Location

ARNAS Garibaldi,

Catania, CT, Italy

Location

Arcispedale S. Anna

Cona, FE, Italy

Location

AOU San Martino IST Istituto Nazionale per la Ricerca sul Cancro IRCCS

Genova, GE, 16132, Italy

Location

Ospedale Misericordia di Grosseto

Grosseto, GR, 58100, Italy

Location

ASL Lucca

Lucca, LU, Italy

Location

Istituto Nazionale dei Tumori IRCCS

Milan, MI, 20133, Italy

Location

Ospedale Ramazzini

Carpi, MO, Italy

Location

Azienda Ospedaliero-Universitaria di Modena - Policlinico

Modena, MO, Italy

Location

AOU Policlinico di Palermo

Palermo, PA, Italy

Location

Ospedale di Camposampiero

Camposampiero, PD, Italy

Location

Istituto Oncologico Veneto IRCCS

Padua, PD, Italy

Location

Centro di Riferimento Oncologico di Aviano (CRO)

Aviano, PN, Italy

Location

AUSL 4

Prato, PO, Italy

Location

Azienda Ospedaliera Universitaria di Parma

Parma, PR, 43126, Italy

Location

CROB-IRCCS di Rionero in Vulture

Rionero in Vulture, PZ, Italy

Location

IRCCS - Azienda Ospedaliera S.M. Nuova

Reggio Emilia, RE, 42123, Italy

Location

Ospedale Civile Santa Chiara

Trento, TN, Italy

Location

I.R.C.C.S. - Fondazione del Piemonte per l'Oncologia

Candiolo, TO, 10060, Italy

Location

Ospedale di Castelfranco Veneto

Castelfranco Veneto, TV, Italy

Location

Azienda ULSS 9 - Ca Foncello

Treviso, TV, Italy

Location

A. O. U. Santa Maria della Misericordia

Udine, UD, Italy

Location

Ospedale di Mirano

Mirano, VE, Italy

Location

Ospedale Sacro Cuore - Don Calabria

Negrar, VR, 37042, Italy

Location

Policlinico G.B. Rossi

Verona, VR, Italy

Location

Clinica Oncologica-Ospedali Riuniti Ancona

Ancona, Italy

Location

Azienda Sanitaria Locale Di Asti

Asti, Italy

Location

Ospedale Dell'Ulss N. 1 Belluno- Ospedale S. Martino Belluno

Belluno, Italy

Location

Ospedale Centrale Di Bolzano

Bolzano, Italy

Location

P.O. Clinicizz. 'Ss. Annunziata' Chieti

Chieti, Italy

Location

Asst Lariana

Como, Italy

Location

A.O. Istituti Ospedalieri - Cremona

Cremona, Italy

Location

Azienda Unità Sanitaria Locale della Romagna

Faenza-Ravenna-Lugo, Italy

Location

Ospedale Lecce - 'V Fazzi' (San Cesario)- Opedale Lecce - 'V.Fazzi'

Lecce, Italy

Location

Ospedale di Livorno

Livorno, Italy

Location

Ospedale San Salvatore

L’Aquila, Italy

Location

UOC Oncologia ASUR AV3 Macerata

Macerata, Italy

Location

I.R.S.T. Srl Irccs

Meldola, Italy

Location

AOR Papardo

Messina, Italy

Location

Ospedale dell'Angelo

Mestre, 30174, Italy

Location

Azienda Ospedaliera Universitaria Federico Ii

Naples, Italy

Location

Istituto Nazionale Tumori - Fondazione Pascale,

Naples, Italy

Location

AOU Maggiore della Carità - SC Oncologia Novara

Novara, Italy

Location

.O. Ospedali Riuniti Marche Nord- Ospedale San Salvatore - Pesaro

Pesaro Fano, Italy

Location

Ospedale "Guglielmo Da Saliceto" Piacenza

Piacenza, Italy

Location

Azienda Ospedaliero-Universitaria Pisana

Pisa, Italy

Location

Azienda Ospedaliera Regionale 'S. Carlo'- Ospedale San Carlo Di Potenza

Potenza, Italy

Location

Presidio Ospedaliero Rimini-Santarcangel- Ospedale "Infermi" Rimini

Rimini, Italy

Location

Azienda Ospedaliera Complesso Ospedaliero San Giovanni - Addolorata

Roma, Italy

Location

Ifo - Istituto Nazionale Tumori Regina Elena (Ire)

Roma, Italy

Location

Ospedale Fatebenefratelli

Roma, Italy

Location

Policlinico Universitario Campus Biomedico

Roma, Italy

Location

U.O.C. di Oncologia Medica Interpresidio PO S.Pertini-S Eugenio-CTO Roma

Roma, Italy

Location

UOC Oncologia Osp. S.Andrea Un. La Sapienza Roma

Roma, Italy

Location

Ao Citta' Della Salute E Della Scienza D- Osp.S. Giov.Battista Molinette

Torino, Italy

Location

Ospedale Di Circolo E Fondazione Macchi - Varese

Varese, Italy

Location

Royal United Hospitals Bath NHS Foundation Trust

Bath, United Kingdom

Location

Blackpool Teaching Hospital

Blackpool, United Kingdom

Location

Raigmore Hospital

Inverness, United Kingdom

Location

Royal Free Hospital

London, United Kingdom

Location

St Bartholomew's Hospital

London, United Kingdom

Location

Hillingdon Hospitals NHS Foundation Trust and Mount Vernon Cancer Centre

Northwood, United Kingdom

Location

Nottingham City Hospital

Nottingham, United Kingdom

Location

Southampton General Hospital

Southampton, United Kingdom

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

avelumab

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Valentina Guarneri, Prof

  University of Padua and Istituto Oncologico Veneto

  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: October 5, 2016
• First Posted: October 6, 2016
• Study Start: June 17, 2016
• Primary Completion: June 1, 2024
• Study Completion: October 9, 2025
• Last Updated: December 12, 2025

Record last verified: 2024-03

Locations

IT (62); GB (8)