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Breast CancerPhase 2BELLININCT03815890

Pre-operative Trial for Breast Cancer With Nivolumab in Combination With Novel IO

A Phase 2 study testing Nivolumab and Ipilimumab in people with Breast Cancer, run by The Netherlands Cancer Institute at 1 site in Netherlands.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

To determine whether short-term pre-operative nivolumab either as monotherapy or in combination with low dose doxorubicin or novel IO combinations can induce immune activation in early BC. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Cancer
What is being tested?
Nivolumab and Ipilimumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
80 participants
Where
1 siteNetherlands
Study dates
4 Oct 2019to 1 Jan 2033
Phase
Phase 2
Are there results?
Not yet: the study is under way

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

  • Signed written informed consent
  • 18 years or older at moment of inclusion;
  • Female gender;
  • WHO performance status 0 or 1;
  • Resectable primary breast cancer stage I-III. Nodal status must be examined by ultrasound, fine needle aspiration, sentinel node biopsy, or FDG-PET scan.
  • The tumors must be:
Show all 13Show fewer
  • at least 10 mm (minimum cT1c) as determined by MRI
  • TNBC defined as ER<10%, HER2-negative OR luminal B defined as ER≥10%, HER2-negative with either Ki67≥20% or PR =<20% OR grade 3. HER2 negative is defined as an IHC score of <2 or 2+ with a negative ISH.
  • For TNBC patients: TIL≥5%
  • For LumB breast cancer patients: TIL≥1%
  • For cohort 3B: N0 status, TN and TIL ≥50%
  • For cohort 4B: N0 status, TNBC and TIL 30-49%
  • For cohort 5B: N0 status, TNBC and TIL ≥50% ● Patients with multifocal/multicentric breast cancer are eligible if triple negative breast cancer histology as well as sufficient TIL percentages (30-49% in cohort 4B, ≥50% in cohort 5B) have been confirmed in all tumor lesions.

Who cannot join

  • evidence or suspicion of metastatic disease. Evaluation of the presence of distant metastases may include chest X-ray, liver ultrasound, isotope bone-scan, CT-scan of chest and abdomen and/or FDG-PET scan, according to local procedures;
  • evidence of a concurrent contralateral or ipsilateral second primary infiltrating breast cancer. Evaluation of the presence of a concurrent second primary breast cancer may include mammography, breast ultrasound and/or MRI breast;
  • other malignancy except carcinoma in situ and basal-cell and squamous carcinoma of the skin, unless the other malignancy was treated ≥5 years ago with curative intent without the use of chemotherapy or radiotherapy
  • previous radiation therapy or chemotherapy;
  • prior treatment with checkpoint inhibitors (including anti- PD1, -PD-L1, -CTLA-4);
  • concurrent anti-cancer treatment, neoadjuvant therapy or another investigational drug;

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

M Kok, MD contact

3120512 ext. 9111

m.kok@nki.nl

I Nederlof contact

3120512 ext. 9111

i.nederlof@nki.nl

Netherlands1 site, 1 recruiting

  • NKI-AVL

    Amsterdam, 1066CX

    M Kok, MD, m.kok@nki.nl

    I Nederlof, i.nederlof@nki.nl

    Recruiting

Other trials in Netherlands

About this study

Official title: Pre-operative Phase II Trial for Breast Cancer With Nivolumab in Combination With Novel IO (BELLINI Trial)

To determine whether short-term pre-operative nivolumab either as monotherapy or in combination with low dose doxorubicin or novel IO combinations can induce immune activation in early BC.

Read the detailed description

The investigators aim to test the activity of nivolumab monotherapy in primary breast tumors in a pre-operative window of opportunity trial. As the data of the investigators generated in the TONIC trial (metastatic TNBC) indicate that low dose doxorubicin may 'prime' the tumor microenvironment (TME) resulting in higher response rates on nivolumab, in addition, cohorts for treatment with nivolumab plus low dose doxorubicin will be opened. Given the emerging data on other immunomodulatory strategies, this platform study allows opening additional cohorts for promising novel immune-oncology (IO) drugs for which a strong efficacy signal has been seen without drug safety issues. The investigators will study the TME and systemic host factors with specific emphasis on immunosuppressive processes that can potentially be targeted by novel IO agents to further optimize BC immunotherapy.

Conditions
Breast Cancer
Being tested
Nivolumab, Ipilimumab
Keywords
pre-operative, triple negative and Luminal B, resectable, stage I-III
Medical subject headings
Breast Neoplasms

What participants receive

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

  • NivolumabDrug

    2 courses 240 mg flat dose

  • IpilimumabDrug

    single dose ipilimumab (1mg/kg) at day 1

  • IpilimumabDrug

    two courses ipilimumab (1mg/kg) at day 1 and 21

Study groups in NCT03815890
Study groupRoleWhat they receive
1A; LumBExperimentalNivolumab
Receives: Drug: Nivolumab
1B; TNBCExperimentalNivolumab
Receives: Drug: Nivolumab
2A; LUMBExperimentalNivolumab and ipilimumab
Receives: Drug: Nivolumab; Drug: Ipilimumab
2B; TNBCExperimentalNivolumab and ipilimumab
Receives: Drug: Nivolumab; Drug: Ipilimumab
3B; TNBC, High TILExperimentalNivolumab and ipilimumab
Receives: Drug: Nivolumab; Drug: Ipilimumab

What is being measured

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

  1. Pathological complete response rate per cohort,

    number of patients with no residual invasively growing tumor cells detected by microscopic examination in breast and axilla

    Measured: up to 3 weeks after surgery, an average of 6 months

Secondary outcomes (3)

  1. Incidence of Treatment-Emergent Adverse Events according to NCI Common Toxicity Criteria version 5.0

    Adverse events in all regimens will be graded according to NCI Common Toxicity Criteria version 5.0.

    Measured: up to 3 weeks after surgery, an average of 6 months

  2. Radiological response rate

    The percentage of patients having a complete response, partial response or stable disease per cohort assessed by MRI

    Measured: At 4 weeks

  3. Immune activation after pre-operative nivolumab, either as monotherapy or in combination with ipilimumab or relatlimab or novel IO combinations.

    Immune activation is defined as either a 2-fold increase in tumor-associated CD8 after pre-operative immunotherapy; and/or a 2-fold increase expression of genes induced by IFNy (determined using mRNA expression levels)

    Measured: within 6 months after surgery

Timeline

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

  1. First posted24 Jan 2019
  2. Study start4 Oct 2019
  3. Primary completion1 Jan 2031 (estimated)
  4. Study completion1 Jan 2033 (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
Non-randomised
Intervention model
Sequential
Model description
Separate cohorts will be opened in this trial. LumB and TNBC tumors will be divided in separate cohorts.More cohorts, e.g. combining nivolumab and novel IO, can open after the start of this trial.
Masking
None (open label)
Enrolment
80 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03815890
Sponsor's protocol ID
M18BEL
Acronym
BELLINI
Status last verified
May 2024
First submitted
13 Dec 2018
Last updated
30 May 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided: to be determined

Publications

  • Nederlof I, Isaeva OI, de Graaf M, Gielen RCAM, Bakker NAM, Rolfes AL, Garner H, Boeckx B, Traets JJH, Mandjes IAM, de Maaker M, van Brussel T, Chelushkin M, Champanhet E, Lopez-Yurda M, van de Vijver K, van den Berg JG, Hofland I, Klioueva N, Mann RM, Loo CE, van Duijnhoven FH, Skinner V, Luykx S, Kerver E, Kalashnikova E, van Dongen MGJ, Sonke GS, Linn SC, Blank CU, de Visser KE, Salgado R, Wessels LFA, Drukker CA, Schumacher TN, Horlings HM, Lambrechts D, Kok M. Neoadjuvant nivolumab or nivolumab plus ipilimumab in early-stage triple-negative breast cancer: a phase 2 adaptive trial. Nat Med. 2024 Nov;30(11):3223-3235. doi: 10.1038/s41591-024-03249-3. Epub 2024 Sep 16.

    PubMed 39284953

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nivolumab and Ipilimumab in people with Breast Cancer, run by The Netherlands Cancer Institute at 1 site in Netherlands.

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 13 inclusion and 6 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: looking for participants now, as of the sponsor's last update on 30 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. 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?

This study is still under way. Results are not available in the source record yet.

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

Contact M Kok, MD (3120512 ext. 9111, m.kok@nki.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pathological complete response rate per cohort, (time frame: up to 3 weeks after surgery, an average of 6 months). 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 NCT03815890, 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 30 May 2024; AzTrials last refreshed its copy on 8 Nov 2026.

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