About this trial

This clinical study is the initiative of the FOSTER (Fight OsteoSarcoma Through European Research) consortium and Gustave Roussy, which is the sponsor. Its aim is to evaluate the biology of tumour in greater depth by collecting samples of the tumour during the biopsy at diagnosis, and blood samples. This study is a platform study that evolves over time. This means that it allows for the evaluation of several treatments or therapeutic strategies within a single clinical trial, which can be modified and adapted over time.

The FOSTER evolving study platform aim to implement a comprehensive strategy of clinical, biological, radiological, therapeutic integrated research from diagnosis to relapse, with the aim to improve survival of osteosarcoma patients of all age, through randomised therapeutic questions at different phase of treatment from diagnosis to relapse. The platform study makes it possible to evaluate several treatments for the same disease, on an ongoing basis, using a main protocol with adaptable arms.

The FOSTER-CabOS trial (part 2 of FOSTER study) is a European Phase III clinical study . It assesses the efficacy of cabozantinib, a tyrosine kinase inhibitor, as a maintenance therapy post-standard treatment in osteosarcoma patients. The trial is randomized against Best Supportive Care to determine the effectiveness of cabozantinib in improving event-free survival. This maintenance therapy aims to prevent relapse among patients who have already received standard treatment for osteosarcoma.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Newly diagnosed, biopsy-proven, high-grade osteosarcoma,

Patient considered medically fit to receive systemic treatment,

Planned systemic therapy according to national guidelines and age

Written informed consent from patients or for minor, from their parents/ legal representatives, before enrolment and any study-related procedure.

Disqualifiers

Patient with a histologically proven and confirmed high-grade osteosarcoma, according to the criteria described in the last World Health Organization (WHO) classification of Soft Tissue and Bone Tumours, after the exclusion of all potential differential diagnoses, either by local pathologists with expertise in bone sarcomas, or through centralized revision in a referral centre, according to national rules.

Age ≥ 4 years old (when able to swallow tablet) ; no upper age limit

First line systemic and local treatment of primary tumour (and metastasis when present) for localised or metastatic osteosarcoma must have been completed according to national guidelines (Mifamurtide is allowed according to centre's practices)

Recovery to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5 Grade 0 or 1 level or recovery to baseline health status preceding the prior treatment from any previous drug/procedure related toxicity (except alopecia, anaemia, and hypothyroidism)

Trial design

Design model

Parallel

Treatments tested in this trial

Experimental group : Cabometyx ® 40mg/m2/day (Max: 60mg/day) , Treatment schedule : Daily**, day 1-28 during 4 weeks (ie. 1 cycle) during 12 cycles
Drug
The intervention evaluated in FOSTER-CabOS is a maintenance treatment strategy using cabozantinib administered after completion of standard first-line therapy for newly diagnosed high-grade osteosarcoma. Unlike induction or salvage treatments, this intervention is introduced in patients without disease progression following standard treatment and aims to prevent or delay relapse. The study specifically evaluates the added value of 12 cycles of cabozantinib as maintenance therapy in a broad population of paediatric and adult osteosarcoma patients. This distinguishes the intervention from other osteosarcoma studies that typically focus on chemotherapy intensification, relapse treatment, or biomarker-selected population.

Treatment groups

530 Participants

are divided into 2 treatment groups

Group A: CabozantinibExperimental treatment 1 intervention

Group B: Best Supportive CareNo intervention 0 interventions

Trial outcomes

Primary outcomes

1

Part 1 of the study (Registration at diagnosis) : event-free survival (EFS)rate of the cohort overall different treatment sequences (First line of treatment) during 3 years .

EFS: time from diagnosis to the first occurrence of progression/relapse (local, regional, or distant), second primary malignancy, or death from any cause; events per investigator assessment with central review when available. Patients without an event are censored at the date of last follow-up.

Time frame

3 years

2

Specific to FOSTER-CabOS (part-2), the first randomization question of the FOSTER evolving study platform: EFS of cabozantinib compared to best supportive care (BSC) as maintenance therapy after first-line chemotherapy

Considering EFS improvement in one or both of the following datasets : * patients in complete remission (CR) at the end of first-line therapy (stratum-1), * the whole randomised dataset, including patients with residual persistent stable disease after first-line treatment (non-resectable primary tumour, or metastatic disease not be completely resected), i.e. strata 1 and 2. Event-free survival (EFS): time from randomisation to first recurrence or progression (local, regional or distant) based on central review evaluation, or death from any cause. A patient without an event is considered censored at his or her last follow-up date.

Time frame

through study completion, an average of 8 year

Secondary outcomes

1

FOSTER evolving study platform (part 1): compliance with the first line conventional chemotherapy.

first line chemotherapy treatment delivery (dose intensity, delays, reductions, early discontinuation, reasons),

Time frame

1 year

2

FOSTER evolving study platform (part 1): proportion of EFS and alive patients after the first line conventional chemotherapy.

EFS: time from diagnosis to the first occurrence of progression/relapse (local, regional, or distant), second primary malignancy, or death from any cause; events per investigator assessment with central review when available. Patients without an event are censored at the date of last follow-up.

Time frame

1 year

3

FOSTER evolving study platform (part 1): the 3-year overall survival (OS) rate of the cohort overall, considering all treatment sequences.

Overall survival (OS): time from diagnosis to death from any cause

Time frame

from diagnosis to 3 years

4

FOSTER evolving study platform (part 1): the 5-year event-free survival (EFS) rate of the cohort overall, considering all treatment sequences.

EFS: time from diagnosis to the first occurrence of progression/relapse (local, regional, or distant), second primary malignancy, or death from any cause; events per investigator assessment with central review when available. Patients without an event are censored at the date of last follow-up.

Time frame

from diagnosis to 5 years