Phase II, multicentre, randomised, open-label trial with MAP +/- denosumab regimen for the treatment of patients with metastatic osteosarcoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Associazione Italiana Ematologia Oncologia Pediatrica

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

19 Dec 2025 → ongoing

Decision date (initial)

2024-12-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

External identifiers

EU CT number

2024-518167-35-01

EudraCT number

2021-002366-41

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

Evaluation of the effectiveness of denosumab in combination with standard chemotherapy in patients with metastatic OS

Secondary objectives 3

1. Overall Survival: OS
2. Safety and toxicity of combination treatment
3. Evaluation of RANK/RANKL expression, of tumor inflammatory infiltrate, both in the primitive tumor and in the metastatic sites reallocated, at diagnosis and after therapy, correlated with the treatment and response to the treatment received

Conditions and MedDRA coding

Patients with Metastatic Osteosarcoma

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. The patient (or his/her legal representative) must be able to read and understand the informed consent form and must provide his/her written informed consent prior to any trial-specific procedure
2. Histologically confirmed diagnosis of high-grade metastatic osteosarcoma at onset
3. Age ≥ 12 years (or having reached skeletal maturity) and ≤ 40 years
4. ECOG Performance status ≤ 2 or Lansky/Karnofsky Score ≥ 40%.
5. Adequate bone marrow function defined as follows: White blood cells >3.0 x 109/L, Absolute neutrophil count >1.5 x 109/L, Platelets >100 x 109/L, Haemoglobin > 9 g/d
6. Adequate liver and kidney function defined as follows: Total bilirubin < 2 Upper Limit of Normality (LSN), AST (SGOT) <3.0 x LSN, ALT (SGPT) <3.0 x LSN, GGT <2.5 x LSN, Blood calcium ≥ 8.0 mg/dl and ≤ 11.5 mg/dl, Creatinine: Creatininemia < 1.5 mg/mL or creatinine clearance of 60 mL/min/1.73m2 for patients with creatinine levels above the normal limit
7. Left Ventricular Ejection Fraction > 50%
8. female patients of childbearing age must have a negative pregnancy test in the 7 days prior to the start of each chemotherapy cycle. Any post-menopausal women must have been amenorrhoeic for at least 12 months to be considered potentially infertile. Potentially fertile male and female patients must agree to use an effective method of contraception during the study

Exclusion criteria 15

1. Medical contraindications to the use of the drugs in the protocol
2. Known history of HIV infection
3. Active or chronic hepatitis B or C requiring treatment with antiviral drugs
4. Evidence of any serious or unstable medical, psychological, or social illness or condition that may compromise the patient's safety and/or compliance with participation in the trial or evaluation of results
5. Known hypersensitivity to the trial drug or its class or to excipients present in the formulation of the trial drugs
6. Known hypersensitivity to calcium or vitamin D
7. Any situation that might jeopardise treatment compliance
8. Subjects with known Central Nervous System metastases
9. Previous treatment with denosumab or other bisphosphonates
10. Hypocalcaemia not controlled with oral calcium supplementation
11. Previous history or evidence of osteonecrosis of the jaw
12. Dental contraindications to the use of denosumab
13. Cardiovascular disease with NYHA status >2. History of myocardial infarction less than 6 months prior to the start of treatment. Patients with unstable angina and severe life-threatening arrhythmia are excluded
14. Medical history of arterial thrombotic or embolic events such as cerebrovascular infarctions (including transient ischaemic attacks - TIA) or pulmonary embolisms in the 6 months prior to the start of trial treatment
15. Pregnancy and/or breastfeeding at the time of diagnosis

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary end-point is 3-year Event Free Survival (EFS)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Associazione Italiana Ematologia Oncologia Pediatrica

Sponsor organisation

Associazione Italiana Ematologia Oncologia Pediatrica

Address

Via Giuseppe Massarenti 11

City

Bologna

Postcode

40138

Country

Italy

Scientific contact point

Organisation

Associazione Italiana Ematologia Oncologia Pediatrica

Contact name

Angela Mastronuzzi

Public contact point

Organisation

Associazione Italiana Ematologia Oncologia Pediatrica

Contact name

Angela Mastronuzzi

Third parties 2

Locations

1 EU/EEA country · 17 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 28 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications