Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ongoing, recruiting
Participants planned
45
Countries
1
Sites
5
Inoperable locally advanced or metastatic TNBC patients, previously treated with anti-PD-L1/PD1- regimens
Evaluate efficacy in terms of Overall Response Rate (ORR) of atezolizumab plus Cyclophosphamide and Vinorelbine in first line patients with inoperable locally advanced or metastatic TNBC, previously treated with anti-PD-L1/PD1- regimens.
Key facts
- Sponsor
- Istituto Europeo Di Oncologia S.r.l.
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Neoplasms [C04]
- Trial duration
- 24 Feb 2025 → ongoing
- Decision date (initial)
- 2024-08-07
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- Fondazione Umberto Veronesi · Roche (supply of atezolizumab) · Ministero della Salute
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy, Safety
Evaluate efficacy in terms of Overall Response Rate (ORR) of atezolizumab plus Cyclophosphamide and Vinorelbine in first line patients with inoperable locally advanced or metastatic TNBC, previously treated with anti-PD-L1/PD1- regimens.
Secondary objectives 2
- Duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety of the combination regimen.
- Correlative and translational objectives will investigate antigen-presenting cell(APC) activation (by flow cytometry and single-cell transcriptomic) and SLT generation (by flow cytometry and single-cell transcriptomic) in the peripheral blood (PB) and in intratumoral biopsies before and after treatment.
Conditions and MedDRA coding
Inoperable locally advanced or metastatic TNBC patients, previously treated with anti-PD-L1/PD1- regimens
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | PT | 10075566 | Triple negative breast cancer | 100000004864 |
| 23.0 | LLT | 10084066 | Triple negative breast cancer metastatic | 10029104 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 6
- Patients with unresectable locally advanced or metastatic, histologically locally documented TNBC (negative for HER2 and ER and PgR).
- Patient with at least one specimen positive (primary site and/or metastatic site) for PD-L1 status as determined by VENTANA PD-L1 SP142 IHC assay, performed locally.
- Prior treatment with anti-PD-L1/PD-1-containing regimens in the neoadjuvant/adjuvant setting.
- Life expectancy ≥12 weeks.
- Measurable disease, as defined by RECIST v1.1.
- Adequate haematologic and end-organ function
Exclusion criteria 5
- Patients with de novo mTNBC OR those who have received 1 or more chemotherapy or targeted systemic therapy (including endocrine therapy) or immunotherapy regimens for advanced disease
- Spinal cord compression not definitively treated with surgery and/or radiation, or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for > 2 weeks prior to the first dose of study treatment (Cycle 1, Day 1).
- Uncontrolled symptomatic pleural effusion, pericardial effusion, or ascites
- Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including significant liver disease
- Significant cardiovascular disease
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- overall response rate
Secondary endpoints 4
- Duration of response (DOR)
- Progression-free survival (PFS)
- Overall survival (OS)
- Safety of the combination regimen
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 3
SUB16414MIG · Substance
- Active substance
- Cyclophosphamide Monohydrate
- Pharmaceutical form
- POWDER FOR SOLUTION FOR INJECTION OR INFUSION
- Route of administration
- INFUSION
- Max daily dose
- 300 mg/m2 milligram(s)/sq. meter
- Max total dose
- 21.6 gm/m2 gram(s)/square meter
- Max treatment duration
- 18 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB00069MIG · Substance
- Active substance
- Vinorelbine
- Pharmaceutical form
- SOFT CAPSULE
- Route of administration
- ORAL
- Max daily dose
- 30 mg milligram(s)
- Max total dose
- 6.48 g gram(s)
- Max treatment duration
- 18 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Tecentriq 840 mg concentrate for solution for infusion
PRD7537923 · Product
- Active substance
- Atezolizumab
- Substance synonyms
- RO5541267
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 840 mg milligram(s)
- Max total dose
- 30.24 g gram(s)
- Max treatment duration
- 18 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01FF05 — -
- Marketing authorisation
- EU/1/17/1220/002
- MA holder
- ROCHE REGISTRATION GMBH
- MA country
- Iceland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Istituto Europeo Di Oncologia S.r.l.
- Sponsor organisation
- Istituto Europeo Di Oncologia S.r.l.
- Address
- Via Giuseppe Ripamonti 435
- City
- Milan
- Postcode
- 20141
- Country
- Italy
Scientific contact point
- Organisation
- Istituto Europeo Di Oncologia S.r.l.
- Contact name
- Elisabetta Munzone
Public contact point
- Organisation
- Istituto Europeo Di Oncologia S.r.l.
- Contact name
- Elisabetta Munzone
Third parties 1
| Organisation | City, country | Duties |
|---|---|---|
| Consorzio Per Valutazioni Biologiche E Farmacologiche ORG-100006471
|
Pavia, Italy | Code 8 |
Locations
1 EU/EEA country · 5 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Italy | Ongoing, recruiting | 45 | 5 |
| Rest of world | — | 0 | — |
Investigational sites
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
UOC Oncologia Medica, Largo Francesco Vito 1, 00168, Rome
Istituto Europeo Di Oncologia S.r.l.
Divisione di Senologia Medica, Via Giuseppe Ripamonti 435, 20141, Milan
Fondazione IRCCS San Gerardo Dei Tintori
Centro Ricerca Fase I, Via Giovanni Battista Pergolesi 33, 20900, Monza
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
UOSD Medicina di Precisione in Senologia, Largo Francesco Vito 1, 00168, Rome
Azienda Sanitaria Locale Br
UOC Oncologia Medica, Senza Numero Civico, Strada Statale 7 Mesagne 1, Brindisi
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 |
|---|---|---|---|---|---|
| Italy | 2025-02-24 | 2025-03-20 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 10 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol_2024-514031-20-00_public | Am. 2 V. 1 |
| Recruitment arrangements (for publication) | K1_recruitment arrangements | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF adults_public | 4 |
| Subject information and informed consent form (for publication) | L2_SIS and ICF Reg UE 2016-679 | 1 |
| Subject information and informed consent form (for publication) | L3_letter to general practitioner | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC tecentriq | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_ciclofosfamide | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_vinorelbina | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_EN_2024-514031-20-00 | 3 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_IT_2024-514031-20-00 | 3 |
Application history
5 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-05-24 | Italy | Acceptable 2024-08-02
|
2024-08-07 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-10-02 | Italy | Acceptable | 2024-10-29 |
| 3 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2024-11-08 | Italy | Acceptable | 2024-11-08 |
| 4 | SUBSTANTIAL MODIFICATION | SM-2 | 2025-02-27 | Italy | Acceptable 2025-04-07
|
2025-04-14 |
| 5 | SUBSTANTIAL MODIFICATION | SM-3 | 2026-03-17 | Italy | Acceptable 2026-04-07
|
2026-04-08 |