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Breast CancerPhase 2BreastImmune03NCT03818685

Evaluate the Clinical Benefit of a Post-operative Treatment Associating Radiotherapy + Nivolumab + Ipilimumab Versus Radiotherapy + Capecitabine for Triple Negative Breast Cancer Patients With Residual Disease

A Phase 2 study testing Nivolumab, Ipilimumab and Capecitabine in people with Breast Cancer and Triple Negative Breast Neoplasms, run by Centre Leon Berard at 17 sites in France.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

To evaluate the clinical benefit of a post-operative adjuvant therapy combining radiotherapy + Nivolumab + Ipilimumab versus radiotherapy + Capecitabine in Triple Negative Breast Cancer (TNBC) patients with residual disease after neoadjuvant chemotherapy. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Nivolumab, Ipilimumab and Capecitabine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
95 participants
Where
17 sitesFrance
Study dates
2 Jul 2019to 1 May 2024
Phase
Phase 2
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 patient 18 years of age on day of signing informed consent form.
  • Histologically proven TNBC defined as follows : HER2 negativity must be confirmed (by one of the following: Fluorescence in situ hybridization (FISH) negative (FISH ratio <2.2), or Immunohistochemistry (IHC): 0-1+, or IHC 2-3+ and FISH-negative (FISH ratio <2.2)) and less than 1% of cells stained by immunohistochemistry (IHC) for ER and PR as per ASCO guidelines.
  • TNBC previously treated by : Standard neoadjuvant chemotherapy containing anthracycline and taxanes and Surgery.
  • TNBC patients currently treated by post-operative radiotherapy as per standard and/or institutional guidelines.
  • No radiological evidence of metastatic disease documented by a CT-Scan of Chest abdomen and pelvis.
  • Residual disease with RCB of Class II or III documented before randomisation using the surgery specimen.
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  • Availability of a representative formalin-fixed paraffin-embedded (FFPE) tumor block from surgery specimen with its histological report.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.
  • Adequate end organ and bone marrow function as defined in protocol. All screening lab tests should be performed within 7 days before C1D1.
  • Absence of significant treatment-related toxicity i.e. > Grade 1 as per CTCAE v5.0, except alopecia (all grades are acceptable), neuropathy (Grade 2 is acceptable) or biological values as defined in protocol.
  • Minimal wash-out period for prior treatments (i.e. minimal delay from last dose of prior treatment to C1D1): any investigational agent > 4 weeks (or 5 half-lives whichever is longer with a minimum of 2 weeks), any monoclonal antibody > 4 weeks, any targeted therapies > 4 weeks, - live vaccine > 4 weeks, systemic steroids at doses higher than 10 mg/day prednisone equivalent or other immunosuppressive agents > 3 weeks, sorivudine or its chemically related analogues such as brivudine > 4 weeks.
  • Women of child-bearing potential must have a negative serum pregnancy test within 7 days before C1D1.
  • Women of child-bearing potential must agree to use 1 effective form of contraception from the time of the negative pregnancy test up to 5 months after the last dose of study drugs.
  • Patient should understand, sign, and date the written voluntary informed consent form at the screening visit prior to any protocol-specific procedures performed.
  • Patient should be able and willing to comply with study visits and procedures as per protocol.
  • Patients must be covered by a medical insurance.

Who cannot join

  • Patient has a metastatic TN breast cancer.
  • Patient has previously received therapy with an anti- PD-1, anti- PD-L1, or anti-CTLA4 or any other immunotherapies.
  • Patient has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone curative therapy and other completely treated prior malignancy if no evidence of disease for ≥ 2 years.
  • Patient presents a contraindication to Nivolumab or Ipilimumab treatment as per respective SPC including known hypersensitivity to one of these study drugs or severe hypersensitivity reaction to any monoclonal antibody.
  • Patient presents a contraindication to Capecitabine treatment as per SPC including : 1) History of severe and unexpected reactions to fluoropyrimidine therapy, 2) Hypersensitivity to Capecitabine or to any of the excipients listed in SPC or fluorouracil, 3) Patients with known complete absence of dihydropyrimidine dehydrogenase activity, 4) Treatment with sorivudine or its chemically related analogues, such as brivudine, 5) any contraindication listed in respective SPC.
  • Patient has active autoimmune disease that has required systemic treatment in the past 3 months before C1D1 or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids at doses higher than 10 mg/d prednisone equivalents or immunosuppressive agents.
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  • Patient requires the use of one of the following forbidden treatment during the study treatment period: any investigational anticancer therapy other than the protocol specified thérapies, any concurrent chemotherapy, immunotherapy, biologic for cancer treatment, other than the ones stated in the protocol. Concurrent use of hormones for non-cancer-related conditions (e.g., insulin for diabetes and hormone replacement therapy) is acceptable, major surger, live vaccines, immunosuppressive agents and immunosuppressive high doses of systemic corticosteroids i.e. doses >10 mg/d prednisone or equivalent, sorivudine or its chemically related analogues such as brivudine and any treatment contra-indicated as per Capecitabine SPC.
  • History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e. bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan.
  • Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 3 months prior to C1D1 unstable arrhythmias or unstable angina, Known Left Ventricular Ejection Fraction (LVEF) < 50%.
  • Patient has a known history of active Bacillus Tuberculosis.
  • Patient has an active infection requiring systemic therapy.
  • Patient has Active hepatitis B (chronic or acute; defined as having a positive hepatitis B surface antigen [HBsAg] test at screening), Active hepatitis C (Patients positive for hepatitis C virus (HCV) antibody are eligible only if PCR is negative for HCV RNA at screening) or Human Immunodeficiency Virus (HIV) infection (HIV 1/2 antibodies).
  • Prior allogeneic bone marrow transplantation or solid organ transplant in the past.
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating Investigator.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the trial, starting with the screening visit through 5 months after the last dose of study drugs.

Trial locations and contacts

17 sites in 1 country.

17 sites in 1 country

France17 sites

  • Institut de Cancérologie de l'Ouest

    Angers, 49055

  • Institut Sainte Catherine

    Avignon

  • CHRU Besançon

    Besançon

  • Centre Francois Baclesse

    Caen

  • Centre d'Oncologie Radiothérapie 37

    Chambray-lès-Tours, 37170

  • Hopital Prive Jean Mermoz

    Lyon, 69008

  • Centre Léon Bérard

    Lyon, 69373

  • Clinique de la Sauvegarde

    Lyon

  • Institut Paoli Calmettes

    Marseille, 13273

  • Centre Antoine Lacassagne

    Nice, 06189

  • Institut Curie

    Paris, 75005

  • GH Pitié-Salpêtrière-Charles Foix

    Paris, 75013

  • Institut Jean Godinot

    Reims, 51056

  • Institut Curie

    Saint-Cloud, 92201

  • Institut de Cancérologie de l'Ouest

    Saint-Herblain, 44805

  • Centre Paul Strauss

    Strasbourg, 67065

  • Hôpital Drôme Ardèche

    Valence, 26000

Other trials in France

About this study

Official title: A Multicenter, Randomised, Open-label Phase II Study to Evaluate the Clinical Benefit of a Post-operative Treatment Associating Radiotherapy + Nivolumab + Ipilimumab Versus Radiotherapy + Capecitabine for Triple Negative Breast Cancer Patients With Residual Disease After Neoadjuvant Chemotherapy

To evaluate the clinical benefit of a post-operative adjuvant therapy combining radiotherapy + Nivolumab + Ipilimumab versus radiotherapy + Capecitabine in Triple Negative Breast Cancer (TNBC) patients with residual disease after neoadjuvant chemotherapy.

Read the detailed description

This trial is an open-label, randomised, multicentric, comparative, Phase II study aiming to evaluate the clinical benefit of a combined treatment associating radiotherapy + Nivolumab + Ipilimumab versus radiotherapy + Capecitabine (standard treatment) in early TNBC patients who have Residual cancer burden (RCB) II or III residual disease after neoadjuvant chemotherapy.

Following validation of eligibility criteria, patients will be randomised (1:1) to receive:

  • Arm A: Nivolumab (360 mg IV, every 3 weeks) for 8 doses and Ipilimumab (1 mg/kg, IV, every 6 weeks or every 2 doses of Nivolumab in case of dose delays) for 4 doses.
  • Arm B: Capecitabine (1000 mg/m2 twice a day, Bis In Die [BID]), 14 days on / 7 days off for 8 cycles.

In both arms, radiotherapy will be administered as per standard practice and has to be initiated one week before C1D1.

Keywords
Residual disease with RCB of Class II or III
Medical subject headings
Breast Neoplasms, Triple Negative Breast Neoplasms

What participants receive

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

  • NivolumabDrug

    Radiotherapy will be maintained in each Arm.

  • IpilimumabDrug

    Radiotherapy will be maintained in each Arm.

  • CapecitabineDrug

    Radiotherapy will be maintained in each Arm.

Study groups in NCT03818685
Study groupRoleWhat they receive
Nivolumab + IpilimumabExperimentalNivolumab (360 mg IV, every 3 weeks) for 8 doses and Ipilimumab (1 mg/kg, IV, every 6 weeks or every 2 doses of Nivolumab in case of dose delays) for 4 doses.
Receives: Drug: Nivolumab; Drug: Ipilimumab
CapecitabineActive comparatorCapecitabine (1000 mg/m2 twice a day, Bis In Die), 14 days on / 7 days off for 8 cycles.
Receives: Drug: Capecitabine

What is being measured

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

  1. Disease free survival (DFS)

    DFS is defined as the time from randomization until the date of the first relapse (local/regional recurrence or distant metastasis) or death (from any cause) whichever comes firsts and regardless of whether the patient withdraws from randomised study treatment or receives another anti-cancer therapy prior to disease relapse.

    Measured: At 2 years

Secondary outcomes (19)

  1. Overall survival

    Overall survival will be measured from the date of randomization to the date of death from any cause.

    Measured: Up to 2 years

  2. Local-regional recurrence

    Local-regional recurrence (LRR) refers to relapse of the primary tumor site

    Measured: Up to 2 years

  3. Distant metastasis

    Distant metastasis is defined as presence of any non-local metastatic sites.

    Measured: Up to 2 years

  4. Disease recurrence/relapse (local or distant)

    Rate of patients with recurrence at 1 year and 2 year post-randomisation as well as time to recurrence will be analysed.

    Measured: Up to 2 years

  5. Adverse Event

    The assessment of safety will be based mainly on the frequency of adverse events based on the common toxicity criteria (CTCAE-V5.0) grade.

    Measured: Up to 2 years

  6. EORTC QLQ C30

    Patient reported outcomes and quality of life will be assessed using the validated following questionnaire: The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ C30). The QLQ-C30 incorporates nine multi-item scales: five functional scales (physical, role, cognitive, emotional, and social); three symptom scales (fatigue, pain, and nausea and vomiting); and a global health and quality-of-life scale. Several single-item symptom measures are also included. See scoring manual at :https://www.eortc.be/qol/files/SCManualQLQ-C30.pdf.

    Measured: At Baseline, every 12 weeks and 30 days after the last dose

  7. Questionnaire EORTC QLQ BR-23

    Patient reported outcomes and quality of life will be assessed using the validated following questionnaire :The European Organization for Research and Treatment of Cancer Breast-Cancer-Specific Quality of Life Questionnaire. See details at :https://www.eortc.be.

    Measured: At Baseline, every 12 weeks and 30 days after the last dose

  8. Questionnaire EORTC QLQ FA-12 Fatigue

    Patient reported outcomes and quality of life will be assessed using the validated following questionnaire : EORTC QLQ FA-12 Fatigue.

    The European Organisation for Research and Treatment of Cancer (EORTC) Group has developed a multidimensional instrument measuring cancer-related fatigue to be used in conjunction with the quality of life core questionnaire (EORTC QLQ-C30). The module EORTC QLQ-FA12 assesses physical, cognitive, and emotional aspects of cancer-related fatigue. See details at :https://www.eortc.be.

    Measured: At Baseline, every 12 weeks and 30 days after the last dose

  9. Questionnaire patient self-rating mood scale.

    Patient reported outcomes and quality of life will be assessed using the following questionnaire : patient self-rating mood scale.

    Measured: At Baseline, every 12 weeks and 30 days after the last dose

  10. Mutational profiles

    To define the molecular characteristics of the tumor' patients: Mutational profiles of tumors (Whole Exome seq,)

    Measured: At Baseline and in case of disease relapse up to 2 years

  11. Copy Number alterations.

    To define the molecular characteristics of the tumor' patients: Copy Number alterations.

    Measured: At Baseline and in case of disease relapse up to 2 years

  12. Loss of heterozygosity.

    To define the molecular characteristics of the tumor' patients: loss of heterozygosity.

    Measured: At Baseline and in case of disease relapse up to 2 years

  13. Circulating tumor DNA

    Circulating tumor DNA detection and analysis will be performed on tumor' patients.

    Measured: At Baseline and in case of disease relapse up to 2 years

  14. Molecular Subtyping

    To define Molecular Subtyping of TNBC (RNAseq) on tumor' patients.

    Measured: At Baseline and in case of disease relapse up to 2 years

  15. Immune monitoring

    To perform Immune monitoring of circulating immune cells and circulating tumor cells on blood sample.

    Measured: At cycle1 (each cycle is 21 days), cycle 2, cycle 5 and 24 months after randomisation or in case of relapse

  16. Circulating growth factors

    To assess levels of circulating growth factors and cytokines on blood sample.

    Measured: At cycle1 (each cycle is 21 days), cycle 2, cycle 5 and 24 months after randomisation or in case of relapse

  17. Cytokines

    To assess levels of cytokines on blood sample.

    Measured: At cycle1 (each cycle is 21 days), cycle 2, cycle 5 and 24 months after randomisation or in case of relapse

  18. PDL1

    To assess the presence in plasma of soluble PDL1.

    Measured: At cycle1 (each cycle is 21 days), cycle 2, cycle 5 and 24 months after randomisation or in case of relapse

  19. PDL2

    To assess the presence in plasma of soluble PDL2.

    Measured: At cycle1 (each cycle is 21 days), cycle 2, cycle 5 and 24 months after randomisation or in case of relapse

Timeline

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

  1. First posted28 Jan 2019
  2. Study start2 Jul 2019
  3. Primary completion15 Mar 2024 (estimated)
  4. Study completion1 May 2024 (estimated)

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
This trial is an open-label, randomised, multicentric, comparative, Phase II study
Masking
None (open label)
Enrolment
95 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03818685
Sponsor's protocol ID
ET17-093 BreastImmune03
Acronym
BreastImmune03
Status last verified
Feb 2024
First submitted
18 Jan 2019
Last updated
12 Feb 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Tredan O, Loirat D, Chabaud S, Toussaint P, Petit T, Viret F, Levy C, Robert A, Grenier J, Mansi L, Spano JP, Patsouris A, Derbel O, Jouannaud C, Ferrero JM, Frenel JS, Molin Y, Doublet L, Heudel PE, Pierga JY, Garin G, Perol D, Bachelot T. Nivolumab in combination with ipilimumab versus capecitabine as post-operative treatment for triple negative breast cancer patients with residual disease after neoadjuvant chemotherapy: a multicentre, randomized, open-label phase II trial - BREASTIMMUNE-03. Breast. 2026 Feb;85:104648. doi: 10.1016/j.breast.2025.104648. Epub 2025 Nov 21.

    PubMed 41314029

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nivolumab, Ipilimumab and Capecitabine in people with Breast Cancer and Triple Negative Breast Neoplasms, run by Centre Leon Berard at 17 sites in France.

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 16 inclusion and 16 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: status not confirmed, as of the sponsor's last update on 12 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in France. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Results are not available in the source record.

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?

Disease free survival (DFS) (time frame: At 2 years). 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 NCT03818685, which also lists 1 linked publication.

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 12 Feb 2024.

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