Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ongoing, recruitment ended
Participants planned
34
Countries
1
Sites
1
Triple negative breast cancer (TNBC) with metastatic disease
To determine the activity of nivolumab after different immune response induction treatments in TNBC patients with metastatic disease
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
- 4 Feb 2020 → ongoing
- Decision date (initial)
- 2025-01-13
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
External identifiers
- EU CT number
- 2024-513217-12-00
- EudraCT number
- 2019-004147-68
- ClinicalTrials.gov
- NCT04159818
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety, Efficacy, Therapy, Pharmacogenomic, Pharmacogenetic
To determine the activity of nivolumab after different immune response induction treatments in TNBC patients with metastatic disease
Secondary objectives 1
- To evaluate the safety of nivolumab as monotherapy or in combination with other immunomodulatory treatments after induction therapy
Conditions and MedDRA coding
Triple negative breast cancer (TNBC) with metastatic disease
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | LLT | 10027475 | Metastatic breast cancer | 10029104 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 7
- Metastatic or incurable locally advanced triple negative breast cancer with confirmation of ER and HER2 negativity (ER <10% and HER2 IHC 0,1+ or 2+ in the absence of amplification)
- Metastatic lesion accessible for histological biopsy
- 18 years or older
- Maximum of three lines of chemotherapy for metastatic disease and with evidence of progression of disease
- WHO performance status of 0 or 1
- Measurable or evaluable disease according to RECIST 1.1
- Disease Free Interval (defined as time between first diagnosis or locoregional recurrence and first metastasis) longer than 1 year. This does not apply to patients with de novo metastatic disease or patients who did not receive (neo)adjuvant chemotherapy
Exclusion criteria 5
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris
- Known history of leptomeningeal disease localization
- History of having received other anticancer therapies within 2 weeks of start of the study drug
- History of immunodeficiency, autoimmune disease, conditions requiring immunosuppression (>10 mgl daily prednisone equivalents) or chronic infections
- Prior treatment with immune checkpoint inhibitors
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Progression-free survival as measured by the proportion of patients free of progression after 6 cycles of nivolumab (PFS1: time from randomization to tumor progression or death from any cause) according to RECIST1.1
Secondary endpoints 6
- Response as measured by the objective response rate (ORR: complete responses or partial responses) according to iRECIST and RECIST1.1
- Clinical benefit as measured by the clinical benefit rate (CBR) according to RECIST 1.1 and iRECIST
- PFS1 according to RECIST 1.1 and iRECIST
- Overall survival (OS: time from nivolumab initiation to death from any cause)
- Percentage of patients with toxicity (CTCAE v5.0) and immune-related toxicity
- PFS as measured by the proportion of patients free of progression after 6 cycles of nivolumab (PFS2: time from randomization to tumor progression or death from any cause). Progression as defined by RECIST 1.1 and iRECIST will be used
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
OPDIVO 10 mg/mL concentrate for solution for infusion.
PRD2941372 · Product
- Active substance
- Nivolumab
- Substance synonyms
- BMS936558, ABP 206
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 480 mg milligram(s)
- Max total dose
- 480 mg milligram(s)
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01FF01 — -
- Marketing authorisation
- EU/1/15/1014/001
- MA holder
- BRISTOL-MYERS SQUIBB PHARMA EEIG
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Comparator 1
Cisplatine 1 mg/ml PCH, concentraat voor oplossing voor infusie
PRD667481 · Product
- Active substance
- Cisplatin
- Substance synonyms
- Cis-diamminedichloroplatinum, (SP-4-2)-cis -diamminedichloroplatinum, CDDP
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 40 mg/m2 milligram(s)/square meter
- Max total dose
- 40 mg/m2 milligram(s)/square meter
- Max treatment duration
- 2 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01XA01 — CISPLATIN
- Marketing authorisation
- RVG 101430
- MA holder
- PHARMACHEMIE BV
- MA country
- Netherlands
- 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 | 34 | 1 |
| Rest of world | — | 0 | — |
Investigational sites
Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting
Medical oncology, Plesmanlaan 121, 1066 CX, Amsterdam
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 | 2020-02-04 | 2020-02-19 | 2022-09-06 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 4 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol N19TON_2024-513217-12-00_REDACTED | 4.0 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements_2024-513217-12-00 | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_2024-513217-12-00 | 4.0 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_SmPC_Cisplatin | 1 |
Application history
1 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2025-01-06 | Netherlands | Acceptable 2025-01-13
|
2025-01-13 |