Overview
Sponsor-declared trial summary
Triple negative breast cancer (TNBC) patients with metastatic disease
To determine the activity of nivolumab after four different immune response induction treatments in TNBC patients with metastatic disease. We hypothesize that short-term induction treatment with radiation, doxorubicin, cyclophosphamide or cisplatin induces an anticancer immune response resulting in increased activity o…
Key facts
- Sponsor
- Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Neoplasms [C04]
- Trial duration
- 8 Sep 2015 → ongoing
- Decision date (initial)
- 2025-01-24
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- Bristol-Myers Squibb International Corporation
External identifiers
- EU CT number
- 2025-520487-18-00
- EudraCT number
- 2015-001969-49
- ClinicalTrials.gov
- NCT02499367
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety, Pharmacogenetic, Efficacy, Therapy, Pharmacogenomic
To determine the activity of nivolumab after four different immune response induction treatments in TNBC patients with metastatic disease. We hypothesize that short-term induction treatment with radiation, doxorubicin, cyclophosphamide or cisplatin induces an anticancer immune response resulting in increased activity of nivolumab as compared to unprimed, single agent nivolumab.
Secondary objectives 1
- To evaluate the safety of nivolumab treatment after short-term induction therapy with radiation, doxorubicin, cyclophosphamide or cisplatin
Conditions and MedDRA coding
Triple negative breast cancer (TNBC) patients with metastatic disease
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 27.0 | LLT | 10027475 | Metastatic breast cancer | 10029104 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 8
- Metastatic ER and HER2 negative breast cancer
- 18 years or older
- Metastatic lesions accessible for histological biopsy
- Maximum of three lines of chemotherapy for metastatic disease
- Evaluable disease according to RECIST 1.1
- WHO performance status 0 or 1
- Subjects with brain metastases are eligible if these have been treated and there is no magnetic resonance imaging (MRI) evidence of progression for at least 4 weeks after treatment is completed and prior to first dose of study drug administration. There must also be no requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration
- Signed written informed consent
Exclusion criteria 4
- Known leptomenigeal disease localization
- History of having recceived other anticancer therapies within 2 weeks of start of the study drug
- History of immunodeficiency, autoimmune disease, conditions requiring immunosuppression (>10 mg daily prednisone equivalents) or chronic infections
- Current pregnancy or breastfeeding
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Progression-free survival (=PFS1, time from randomization to tumor progression or death from any cause). Progression as defined by RECIST 1.1 will be used.
Secondary endpoints 6
- Progression-free survival (=PFS1, time from randomization to tumor progression or death from any cause). Progression as defined by modified RECIST 1.1 for immune-based therapeutics (iRECIST) will be used.
- Progression-free survival (=PFS2, time from nivolumab treatment initiation to tumor progression). Progression as defined by RECIST 1.1 and iRECIST will be used.
- Overall response rate ORR (complete response CR or partial response PR) according to RECIST 1.1 and iRECIST. ORR1 (relative to randomization) and ORR2 (relative to nivolumab initiation) will be used.
- Clinical benefit rate (CR+PR+stable disease ≥ 6 months and CR+PR+stable disease ≥ 3 months) according to RECIST 1.1 and iRECIST. CBR1 (relative to randomization) and CBR2 (relative to nivolumab initiation) will be used.
- Overall survival (OS, time from nivolumab initiation to death from any cause).
- Percentage of patients with toxicity (classified according to CTCAE v4.0) and immune-related toxicity.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
OPDIVO 10 mg/mL concentrate for solution for infusion.
PRD2941375 · Product
- Active substance
- Nivolumab
- Substance synonyms
- BMS936558, ABP 206
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 3 mg/kg milligram(s)/kilogram
- Max total dose
- 3 mg/kg milligram(s)/kilogram
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01FF01 — -
- Marketing authorisation
- EU/1/15/1014/002
- MA holder
- BRISTOL-MYERS SQUIBB PHARMA EEIG
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting
- Sponsor organisation
- Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting
- Address
- Plesmanlaan 121
- City
- Amsterdam
- Postcode
- 1066 CX
- Country
- Netherlands
Scientific contact point
- Organisation
- Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting
- Contact name
- Marleen kok
Public contact point
- Organisation
- Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting
- Contact name
- Marleen kok
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Netherlands | Ongoing, recruitment ended | 84 | 1 |
| Rest of world | — | 0 | — |
Investigational sites
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Netherlands | 2015-09-08 | 2015-09-14 | 2019-07-05 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 3 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol_2025-520487-18-00_ N15TON_REDACTED | 6.0 |
| Recruitment arrangements (for publication) | K1_Recruitment procedure_2025-520487-18-00 | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_2025-520487-18-00_N15TON_REDACTED | 5.0 |
Application history
1 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2025-01-14 | Netherlands | Acceptable 2025-01-24
|
2025-01-24 |