Treatment protocol for osteosarcomas in children, adolescents and adults including a randomized trial and biological studies

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Unicancer

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

19 Mar 2007 → ongoing

Decision date (initial)

2024-08-12

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

CHUGAI · NOVARTIS · INCA

External identifiers

EU CT number

2024-514756-32-00

EudraCT number

2006-003377-27

ClinicalTrials.gov

NCT00470223

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenetic, Pharmacogenomic, Therapy, Efficacy, Safety, Pharmacokinetic

Compare the progression-free survival of patients with osteosarcoma treated with combination chemotherapy and surgery with or without zoledronic acid

Secondary objectives 2

1. • To assess the impact of Zometa® on overall survival, histological response to chemotherapy, immediate and long-term tolerability of treatment, in particular renal tolerance, orthopaedic complications and growth, bone density and quality of life.
2. • To study on biological samples the gene expression profiles of patients with good and poor response, the differences in tissue-array expression profiles of adult and pediatric patients, the prognostic value of angiogenesis markers such as FGF and VEGF, the expression of tumour antigens, the effect of Zometa® on lymphocyte populations, in particular , the consequences of treatment with biphosphonates on bone metabolism and growth, the impact of the pharmacogenetics of methotrexate, and the pharmacokinetics of Zometa® in children and young adults

Conditions and MedDRA coding

High grade osteosarcoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Patient with histologically proven high-grade osteosarcoma
2. 5 years ≤ Age ≤ 50 years
3. No contraindication to the treatments envisaged
4. Not previously treated with chemo or radiotherapy for this tumour or another cancer
5. Have signed the informed consent form. For unemancipated minors, authorisation will be given by the holders of parental authority. This authorisation may be given by only one of the holders of parental authority if the other holder is unable to give his or her authorisation within a timeframe compatible with the methodological requirements for carrying out the research. Minors will receive information adapted to their capacity for understanding.
6. For which long-term follow-up is possible
7. and declared to the registration centre as soon as consent has been obtained, at the latest on the 3rd day of the first course of chemotherapy.
8. Effective contraception for women of childbearing age
9. Membership of a social security scheme

Exclusion criteria 15

1. Low-grade osteosarcoma
2. Small cell osteosarcoma
3. Maxillary osteosarcoma (due to the risk of osteonecrosis of the maxilla associated with biphosphonates)
4. Osteosarcoma operated on from the outset
5. Polymetastatic osteosarcoma with metastases considered a priori inoperable even after reduction with chemotherapy
6. Extraosseous osteosarcoma
7. Chronic disease incompatible with the protocol
8. Shortening fraction less than 28% or isotopic or echographic LVEF < 50% before treatment for patients to be treated according to the API-AI protocol
9. Calculated creatinine clearance < 70 mL/min/1.73 m².
10. Bilirubin > 2 x upper normal value
11. Current or recent dental problem (< 6 weeks) including any severe infection of the teeth or jaw (mandible and maxilla), dental trauma, dental or stomatological surgery (implants). Simple dental treatment is not a contraindication. A delay of 3 weeks is required between dental avulsion and the administration of Zometa®.
12. History of osteonecrosis of the jawbone or exposure of bone or delayed healing after dental surgery.
13. Any medical abnormality incompatible with the treatments planned in this study.
14. Pregnancy or breast-feeding
15. Patients who, for family, social, geographical or psychological reasons, cannot be monitored regularly.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Event-free survival at 3 years.

Secondary endpoints 5

1. Overall survival,
2. Histological response,
3. Short-term (NCI-CTC v3) and long-term toxicity,
4. Bone metabolism,
5. Quality of life.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Unicancer

Sponsor organisation

Unicancer

Address

101 Rue De Tolbiac

City

Paris Cedex 13

Postcode

75654

Country

France

Scientific contact point

Organisation

Unicancer

Contact name

Nourredine AIT RAHMOUNE

Public contact point

Organisation

Unicancer

Contact name

Nourredine AIT RAHMOUNE

Locations

1 EU/EEA country · 54 investigational sites

By country

Investigational sites

Country notifications

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

Application history

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