2023-505575-69-01招募中3 期
Fight Osteosarcoma Through European Research evolving study platform from diagnosis to relapse (FOSTER evolving study platform)
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 508
- 试验地点
- 88
- 主要终点
- For FOSTER evolving study platform: 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. The 3-year EFS rate will be estimated using Kaplan–Meier methods.
研究概览
简要总结
For FOSTER evolving study platform: To assess the 3-year event-free survival (EFS) rate of the cohort overalldifferent treatment sequences. For FOSTER-CabOS (first randomization) : To assess efficacy in terms of 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.
入排标准
- 年龄范围
- 0 years 至 65+ years（18-64 Years, 65+ Years, 0-17 Years）
- 接受健康志愿者
- 否
入选标准
- •For FOSTER evolving study platform -
- •Newly diagnosed, biopsy-proven, high-grade osteosarcoma
- •For FOSTER-CabOS (first randomization) -
- •Performance status < 2 for patient adult, or >70 using Karnofsky or Lansky performance scores.
- •For FOSTER-CabOS (first randomization) -
- •Interval between the last treatment either chemotherapy administration or surgical procedures or radiotherapy or thermoablation, (whichever occurred last) and the date of randomisation should be at least 4 weeks but no longer than 2 months
- •For FOSTER-CabOS (first randomization) -
- •Disease in complete remission or with residual persistent stable disease according to RECIST criteria before randomisation (please refer 7.3.4 for the definition of the residual persistent stable disease)
- •For FOSTER-CabOS (first randomization) -
- •Patient fit to undergo protocol treatment and follow-up
- •For FOSTER-CabOS (first randomization) -
- •Adequate cardiac function: Left Ventricular Ejection Fraction (LVEF) ≥50% and/or fractional shortening (FS) >28% at baseline as determined by echocardiography or multigated acquisition (MUGA) scan (performed only if echocardiography is not feasible)
- •For FOSTER-CabOS (first randomization) -
- •Adequately controlled blood pressure (BP) with or without antihypertensive medications: BP 95th percentile for sex, age and height/length at screening (as per NHLBI (National Heart, Lung and Blood Institute) guidelines) and no change in antihypertensive medications within 1 week prior to start of treatment (C1D1). Patients aged >18 years should have a BP ≤150/90 mmHg at screening and no change in antihypertensive therapy within 1 week prior to C1D1
- •For FOSTER-CabOS (first randomization) -
- •Screening laboratory values must meet the following criteria (according to CTCAE v5) and should be obtained within 7 days prior to randomisation - Absolute neutrophil count ≥ 1 x 109/L - Platelets ≥ 100 x 109/L - Haemoglobin ≥ 8.0 g/dL (a hemoglobin of less than 8.0 g/dl is acceptable if it is corrected by growth factor or transfusion before C1D1) - Serum creatinine ≤ 1.5 x ULN or based on age/gender. If serum creatinine is greater than maximum serum creatinine for age/gender as described, then creatinine clearance (or radioisotope Glomerular Filtration Rate (GFR)) must be >60 ml/min/1.73 m2 - Urine dipstick < 2+ for proteinuria. Patients who have ≥2+ proteinuria on dipstick urinalysis should undergo a spot Protein/Creatinine ratio test that should be grade 2 per CTCAE v5.0 - No clinical evidence of nephrotic syndrome - Alanine Aminotransferase/Aspartate Aminotransferase (ALT/AST) ≤ 2.5 x Upper limit of normal (ULN) in the absence of liver metastases or ≤ 5.0 x ULN in the presence of liver metastases - Total bilirubin ≤ 1.5 x ULN (except Gilbert Syndrome: < 3.0 mg/dL) or ≤ 5.0 x ULN in the presence of liver metastases - Alkaline phosphatase (PAL) ≤2.5 x ULN (≤5 x ULN in patient with liver involvement of their cancer). If Alkaline phosphatase > 2.5 ULN, Gamma-Glutamyl Transferase GGT tests must be performed; GGT < 1.5 x ULN - Lipase ≤1.5 x ULN - INR (International Normalized Ratio) /PTT (Partial Thromboplatin Time) ≤1.5 x ULN
- •For FOSTER-CabOS (first randomization) -
- •Patients who are therapeutically treated with an agent such as warfarin or heparin/ Low-molecular-weight heparin (LMWH) will be allowed to participate provided that no prior evidence of underlying abnormality in coagulation parameters exists.
- •For FOSTER-CabOS (first randomization) -
- •Women of childbearing potential or young women of chilbearing potential and who started their puberty (menarche) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of Human Chorionic Gonadotropin (HCG)) done within 7 days prior to randomisation.
- •For FOSTER-CabOS (first randomization) - 14.Effective methods of contraception should be used by male and female patients and their partners during therapy, and for at least 4 months after completing therapy. Because oral contraceptives might not be considered as “effective methods of contraception”, they should be used together with another method, such as a barrier method, according to age and gynaecologist advice.
- •For FOSTER evolving study platform -
- •Patient considered medically fit to receive systemic treatment
- •For FOSTER-CabOS (first randomization) -
- •Provision of dated and signed written informed consent for the randomised trial prior to any study specific procedures, sampling and analyses.
- •For FOSTER-CabOS (first randomization) -
- •Affiliation to a social insurance or equivalent regimen (if required in the country).
- •For FOSTER evolving study platform -
- •Planned systemic therapy according to national guidelines and age
- •For FOSTER evolving study platform -
- •Written informed consent from patients and/or their parents/ guardians before enrolment and any study-related procedure.
- •For FOSTER evolving study platform -
- •Affiliation to a social insurance or equivalent regimen (if required in the country)
- •For FOSTER-CabOS (first randomization)-
- •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.
- •For FOSTER-CabOS (first randomization) -
- •Age ≥ 4 years old (when able to swallow tablet) ; no upper age limit
- •For FOSTER-CabOS (first randomization) -
- •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)
- •For FOSTER-CabOS (first randomization) -
- •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)
排除标准
- •For FOSTER evolving study platform -
- •Low-grade osteosarcoma, parosteal or periosteal osteosarcoma , small cell osteosarcome
- •For FOSTER-CabOS (first randomization) -
- •Clinically significant unrelated systemic illness (e.g., serious infection or significant cardiac, pulmonary, hepatic, or other organ dysfunction) that would compromise the patient's ability to tolerate study treatment or would likely interfere with study procedures or results;
- •For FOSTER-CabOS (first randomization) -
- •Use of prohibited concomitant and/or concurrent medications (see section “Prohibited concomitant/concurrent treatments)
- •For FOSTER-CabOS (first randomization) -
- •Progressive disease at any site during initial pre- and/or post-operative chemotherapy, confirmed before randomisation time. With exception of patients with progressive disease limited to the primary tumour during pre-operative chemotherapy, if complete resection is achieved at surgery.
- •For FOSTER-CabOS (first randomization) -
- •Pregnant or breastfeeding women or intending to become pregnant during the clinical investigation.
- •For FOSTER-CabOS (first randomization) -
- •Patients with any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
- •For FOSTER-CabOS (first randomization) -
- •Patients with history of non-compliance to medical regimens or unwilling or unable to comply with the protocol.
- •For FOSTER-CabOS (first randomization) -
- •Patient under guardianship or deprived of his liberty by a judicial or administrative decision or incapable of giving its consent
- •For FOSTER-CabOS (first randomization) -
- •Prior treatment with any Vascular Endothelial Growth Factor (VEGFR) inhibitor (thus, any prior exposure to sunitinib, sorafenib, pazopanib, regorafenib, bevacizumab, or other VEGFR inhibitor);
- •For FOSTER-CabOS (first randomization) -
- •Cardiovascular dysfunction
- •For FOSTER-CabOS (first randomization) -
- •Uncontrolled hypertension > the 95th percentile despite optimal treatment (for adults, systolic blood pressure > 150mmHg or diastolic pressure > 90 mmHg despite optimal treatment)
- •For FOSTER-CabOS (first randomization) -
- •Active hepatitis B or C or chronic hepatitis B or C requiring treatment with antiviral therapy;
- •For FOSTER-CabOS (first randomization) -
- •Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism within the last 6 months before the first study drug administration;
- •For FOSTER-CabOS (first randomization) -
- •Major surgical procedure or significant traumatic injury within 3 weeks before the first study drug administration. Note: Adequate wound healing after major surgery must be clinically assessed, independent of time elapsed for eligibility.
- •For FOSTER-CabOS (first randomization) -
- •Ongoing infection > Grade 2 according to NCI-CTCAE v5, unless fully recovered prior cycle1 day1;
- •For FOSTER-CabOS (first randomization) -
- •Known history of human immunodeficiency virus (HIV) infection;
- •For FOSTER-CabOS (first randomization) -
- •Known hypersensitivity to the active substance Investigational Medicinal Product or to any of the excipients
- •For FOSTER-CabOS (first randomization) -
- •Dehydration according to NCI-CTC v5 Grade >1
- •For FOSTER-CabOS (first randomization) -
- •Difficulties to swallow oral medication and/or any malabsorption condition and/or any Gastrointestinal (GI) disease that may significantly alter the absorption of cabozantinib (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhoea, malabsorption syndrome, or small bowel resection);
- •For FOSTER-CabOS (first randomization) -
- •Patients with a seizure disorder requiring medication;
- •For FOSTER-CabOS (first randomization) -
- •Interstitial lung disease with ongoing signs and symptoms at the time of informed consent;
- •For FOSTER-CabOS (first randomization) -
- •Non-healing wound, non-healing ulcer, or non-healing bone fracture
- •For FOSTER-CabOS (first randomization) -
- •Patients with evidence or history of any bleeding diathesis, irrespective of severity;
- •For FOSTER-CabOS (first randomization) -
- •Any haemorrhage or bleeding event ≥ CTCAE v5 Grade 3 within 4 weeks prior to the first study drug administration;
研究组 & 干预措施
CABOMETYX 20 mg film-coated tablets, CABOMETYX 40 mg film-coated tablets, CABOMETYX 60 mg film-coated tablets
Test
干预措施: CABOMETYX 40 mg film-coated tablets (Drug)
CABOMETYX 20 mg film-coated tablets, CABOMETYX 40 mg film-coated tablets, CABOMETYX 60 mg film-coated tablets
Test
干预措施: CABOMETYX 60 mg film-coated tablets (Drug)
CABOMETYX 20 mg film-coated tablets, CABOMETYX 40 mg film-coated tablets, CABOMETYX 60 mg film-coated tablets
Test
干预措施: CABOMETYX 20 mg film-coated tablets (Drug)
结局指标
主要结局
For FOSTER evolving study platform: 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. The 3-year EFS rate will be estimated using Kaplan–Meier methods.
For FOSTER evolving study platform: 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. The 3-year EFS rate will be estimated using Kaplan–Meier methods.
For FOSTER-CabOS (first randomization) : 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.
For FOSTER-CabOS (first randomization) : 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.
次要结局
- For FOSTER evolving study platform : Feasibility and compliance: screening-to-enrolment rate, consent rate, time to enrolment/treatment start, CRF data completeness (baseline/induction), first line chemotherapy treatment delivery (dose intensity, delays, reductions, early discontinuation, reasons), adherence to scheduled follow-up visits.
- For FOSTER evolving study platform : Disease-free patient: A patient who remains disease-free and alive at the completion of the first line conventional chemotherapy, as determined by clinical and radiological assessments conducted between 6 and 10 months after the start of treatment.
- For FOSTER evolving study platform : Overall survival (OS): time from diagnosis to death from any cause
- For FOSTER evolving study platform : 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.
- For FOSTER evolving study platform : Adverse events: incidence of treatment-emergent adverse events (AEs), serious adverse events (SAEs), and treatment-related mortality during induction.
- For FOSTER evolving study platform : Quality of life and functional outcome: QoL assessed by EORTC QLQ-C30 and PedsQL; functional outcome assessed by TESS at predefined timepoints.
- For FOSTER evolving study platform : Prognostic factors: association of clinical and biological variables (including G1/G2 signature at diagnosis) with OS and EFS via multivariable-adjusted Cox models. Results reported as hazard ratios (HRs) with 95% confidence intervals (CIs) (pre-specified covariates and handling of missing data per SAP).
- For FOSTER-CabOS (first randomization) : Adverse events (AE), a real-time reporting of any AE of grade 3+ is planned during the first 8 weeks in the first 20 patients receiving mifamurtide.
- For FOSTER-CabOS (first randomization) : Quality-adjusted time without symptoms of disease or toxicity (Quality-adjusted Time Without Symptoms of disease recurrence or Toxicity (Q-TWiST)) computed from survival times (OS and Event Free Survival (EFS) duration) and adverse events data (duration of time spent with a severe-AE before progression/recurrence)
- For FOSTER-CabOS (first randomization) : Disease status based on initial staging and complete remission after first line treatment histological response; biological subgroups in particular G1/G2 diagnostic RNAseq signature; type of first line chemotherapy; use of mifamurtide ; age, metastatic status at diagnosis.
- For FOSTER-CabOS (first randomization) : Heigh and growth plate
- For FOSTER-CabOS (first randomization) : Description of would healing complication
- For FOSTER evolving study platform : (if applicable) Comparisons between treatment sequences: comparisons of survival overall treatment sequences using Cox proportional hazards models (with multivariable adjustment) and Kaplan–Meier estimates with log-rank tests. The absence of randomization may also imply the use of weighting methods such as Inverse Probability of Censoring Weighting ( IPCW).
- For FOSTER evolving study platform : ctDNA analyses.
- For FOSTER evolving study platform : Radiomics analyses.
- For FOSTER evolving study platform : Imaging-based definition of lung metastases (number, characteristics, location) derived by AI and compared with anatomic pathology.
- For FOSTER evolving study platform : Incorporation of questionnaire results into clinical interpretation.
- For FOSTER evolving study platform : Number of countries participating in the FOSTER-Evolving study platform over time.
- For FOSTER evolving study platform : Number of samples collected per registered patient.
- For FOSTER evolving study platform : Number and type of analyses performed per registered patient.
- For FOSTER evolving study platform : Number and type of imaging studies centralized in the imaging repository per registered patient
- For FOSTER evolving study platform : Growth plate maturation through bone age
- For FOSTER-CabOS (first randomization) : Group comparison on EFS and OS (OS being defined as the time from randomisation to death from any cause. The observation will be censored at the date of last follow-up in patients alive and free of event) « Cabozantinib vs BSC » - According to G1/G2 group - According to ctDNA content at daignosis - According to composition of the TME and cancer cells in the diagnosis biopsy
- For FOSTER-CabOS (first randomization) : Growth plate maturation through bone age
- For FOSTER-CabOS (first randomization) : Thickness of the growth plate
- For FOSTER-CabOS (first randomization) : IGF1 value
研究者
Bureau projet Promotion- DRC -Regulatory Affairs Officer
Scientific
Institut Gustave Roussy
研究点 (88)
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