Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Authorised, recruiting
Participants planned
67
Countries
1
Sites
4
bone sarcoma
To evaluate EFS (Event Free Survival) in patients with osteosarcoma and Ewing's sarcoma at high risk of relapse compared with that found in historical controls.
Key facts
- Sponsor
- Istituto Ortopedico Rizzoli
- Participant type
- Pediatric, Patients
- Age range
- 0-17 years, 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Musculoskeletal Diseases [C05]
- Trial duration
- 30 Jul 2024 → ongoing
- Decision date (initial)
- 2024-07-29
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- Istituto Ortopedico Rizzoli
External identifiers
- EU CT number
- 2024-515639-32-00
- EudraCT number
- 2020-002579-37
- ClinicalTrials.gov
- NCT04758000
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety, Efficacy
To evaluate EFS (Event Free Survival) in patients with osteosarcoma and Ewing's sarcoma at high risk of relapse compared with that found in historical controls.
Secondary objectives 1
- Evaluate metformin toxicity (blood tests, clinical assessment), therapy compliance with age-adjusted EORTC QLQ-C30 questionnaire for adults.
Conditions and MedDRA coding
bone sarcoma
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | HLT | 10039498 | Bone sarcomas | 10029104 |
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | 1 overal design
|
2 | None | Cohort 1: Patients with localized osteosarcoma with necrosis ≤ 60%: of the primary tumor at the time of surgery after preoperative chemotherapy Cohort 2: Patients in complete remission after relapse from osteosarcoma or Ewing's sarcoma |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 9
- Age ≥ 10 years
- Body weight ≥ 30 kg
- Patients with localized Osteosarcoma with necrosis ≤ 60% at the end of postoperative chemotherapy (within 45 days of completion)
- Patients with osteosarcoma or Ewing's sarcoma rendered disease-free after first relapse (within 45 gg of surgery or chemotherapy termination)
- Patients not included in other protocols
- Patients able to swallow
- Screening within 30 days of chemotherapy termination (or relapse surgery)
- Starting treatment within 30 from screening
- Normal renal function (creatinine <1.3 mg/L, creatinine clearance ≥70 mL/min) and liver function (serum total bilirubin <1.2 mg/dL, except patients with Gilbert syndrome), AST and ALT <1.8 times the value above the normal range
Exclusion criteria 9
- Type I or II diabetes
- Patient with metastatic disease
- Patients with hypersensitivity to the active ingredient or any of the excipients Patients with any type of acute metabolic acidosis (such as lactic acidosis, diabetic ketoacidosis)
- Patients with renal insufficiency (GFR < 70 ml/min).
- Patients with acute conditions potentially affecting renal function such as dehydration, severe infection, shock
- Patients with liver failure, acute alcohol intoxication, alcoholism.
- Patients with conditions that can cause tissue hypoxia: decompensated heart failure, respiratory failure, recent myocardial infarction, shock.
- Patient who does not fit the inclusion criteria
- Pregnant or lactating women or women of childbearing age who cannot rule out pregnancy status (possibly ruled out by serological pregnancy test (hCG research)), according to CTFG recommendations.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Event Free Survival
Secondary endpoints 2
- unexpected metformin toxicity
- patient therapy compliance with EORTC QLQ-C30 questionnaire
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
—
SCP10310250 · ATC
- Route of administration
- ORAL
- Max daily dose
- 250 mg milligram(s)
- Max total dose
- 850 mg milligram(s)
- Max treatment duration
- 48 Month(s)
- Authorisation status
- Authorised
- ATC code
- A10BA02 — METFORMIN
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Metformin used as maintenance therapy in bone sarcomas at high risk of relapse
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Istituto Ortopedico Rizzoli
- Sponsor organisation
- Istituto Ortopedico Rizzoli
- Address
- Via Di Barbiano 1/10
- City
- Bologna
- Postcode
- 40136
- Country
- Italy
Scientific contact point
- Organisation
- Istituto Ortopedico Rizzoli
- Contact name
- Martina Piccinni Leopardi
Public contact point
- Organisation
- Istituto Ortopedico Rizzoli
- Contact name
- Martina Piccinni Leopardi
Locations
1 EU/EEA country · 4 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Italy | Authorised, recruiting | 67 | 4 |
| Rest of world | — | 0 | — |
Investigational sites
Istituto Ortopedico Rizzoli
Chemotherapy Unit, Via Di Barbiano 1/10, 40136, Bologna
Hospital Santa Maria Della Misericordia
Oncoematologia pediatric, Piazzale Giorgio Menghini 1, 06129, Perugia
Azienda Ospedaliero Universitaria Pisana
Pediatric Onco-Hematology Unit, Via Roma 67, 56126, Pisa
Centro Di Riferimento Oncologico Di Aviano
Oncology Unit, Via Franco Gallini 2, 33081, Aviano
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 | 2024-07-30 |
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_Protocollo 2024-515639-32-00_redacted | 3.0 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangement_Blank document | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF study adults_v 1_2 dated 30_10_2020_redacted | 1.2 |
| Subject information and informed consent form (for publication) | L2_SIS and ICF study minor_v 2_1_ dated 30_10_2020_redacted | 2.1 |
| Subject information and informed consent form (for publication) | L3_SIS and ICF study 11-17y_ v 1_0 dated 16_04_2020_redacted | 1 |
| Subject information and informed consent form (for publication) | L4_SIS and ICF study minor 11y_v 1_0 dated 27_10_2022 | 1 |
| Subject information and informed consent form (for publication) | L5_SIS and ICF privacy adults_v dated 20_07_2020_redacted | 1 |
| Subject information and informed consent form (for publication) | L6_SIS and ICF privacy minors_v dated 30_10_2020_redacted | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E1_SmPC Zuglimet 2024-515639-32-00 | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis IT 2024-515639-32-00_redacted | 2.3 |
Application history
1 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-06-24 | Italy | Acceptable 2024-07-23
|
2024-07-29 |