Regorafenib for Bone sarcoma | Osteosarcoma metastatic | Chondrosarcoma metastatic | Ewing sarcoma metastatic | Chordoma | CIC-rearranged sarcoma

Inclusion criteria

• {"criterion_text":"- Patients must have a histologically and molecularly confirmed diagnosis of CIC-rearranged sarcoma (either bone or soft tissue) with available Formalin Fixed Paraffin Embedded (FFPE) blocks obtained for further research purposes;\n- Patients with confirmed disease progression at study entry. The “baseline” radiological evaluation should demonstrate disease progression by RECIST V 1.1 when compared to a prior disease assessment done within a prior period of 3 month prior to screening Note: radiographic progression of disease will be based on at least 2 sets of scans (either MRI or CT) in the 3-month to or during screening in which radiographic progression of disease, as defined by RECIST, is demonstrated. No central review of scans (either MRIs or CTs) will be required for study eligibility; these scans must be sent for central review within 10 days after start of treatment\n- Metastatic disease and/or locally advanced disease not amenable to surgical resection or radiation with curative intent;\n- Patients must have measurable disease (outside any previous irradiated field) defined as at least one unidimensionally lesion that can be accurately measured as ≥ 10 mm with CT scan according to RECIST V1.1 for all cohorts;\n- Prior treatment : no more than three prior chemotherapy regimen for metastatic disease or locally advanced for CIC-rearranged sarcoma (neo-adjuvant /maintenance therapy are not counted towards this requirement). First line patients must have been previously treated with a previous (neo)adjuvant chemotherapy regimen. At least 4 weeks since last chemotherapy (6 weeks in case of nitrosoureas and mitomycin C), immunotherapy or any other pharmacological treatment and/or radiotherapy;\n- Age ≥ 10\n- Body Surface Area ≥ 1.30 m²\n- Life expectancy of greater than 3 months\n- ECOG performance status < 2 (Karnofsky ≥ 60%) for adults patients\n- Karnofsky scale ≥ 60 % for children aged > 12 years old / Lansky scale ≥ 60 % for children aged ≤ 12 years old\n- Patients must have adequate bone marrow, renal, and hepatic function, as evidenced by the following within 7 days of study treatment initiation : normal organ function as defined below : a. Absolute neutrophil count ≥ 1.5 Giga/L b. Platelets ≥ 100 Giga/L c. Hemoglobin≥ 9 g/dL d. Serum creatinin ≤ 1.5 x ULN e. Glomerular filtration rate (GFR) ≥30 ml/min/1.73m2 according to the modified Diet in Renal Disease (MDRD) abbreviated formula f. AST and ALT ≤2.5 x ULN ( ≤5.0 × ULN for patients with liver involvement of their cancer g. Bilirubin ≤1.5 X ULN h. Alkaline phosphatase ≤2.5 x ULN (≤5 x ULN in patient with liver involvement of their cancer). If Alkaline phosphatase > 2.5 ULN, hepatic isoenzymes 5-nucleotidase or GGT tests must be performed; hepatic isoenzymes 5-nucleotidase must be within the normal range and/or GGT < 1.5 x ULN i. lipase ≤1.5 x ULN. j. Spot urine must not show ≥ 1 “+”protein in urine or the patient will require a repeat urine analysis. If repeat urinalysis shows 1 “+” protein or more, a 24-hour urine collection will be required and must show total protein excretion <1000 mg/24 hours\n- INR/PTT ≤1.5 x ULN; Patients who are therapeutically treated with an agent such as warfarin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in coagulation parameters exists. Close monitoring of at least weekly evaluations will be performed until INR/PTT is stable based on a measurement that is pre-dose as defined by the local standard of care\n- Recovery to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4.0 Grade 0 or 1 level or recovery to baseline preceding the prior treatment from any previous drug/procedure related toxicity (except alopecia, anemia, and hypothyroidism);\n- Women of childbearing potential and male patients must agree to use adequate contraception for the duration of study participation and up to 3 months following completion of therapy;\n- Women of childbearing potential must have a negative serum β-HCG pregnancy test within 7 days prior randomization and/or urine pregnancy test within 48 hours before the first administration of the study treatment;\n- Signed informed consent form by adult patients and/orpatients parents/legal representatives (if age < 18 years) and age appropriate assent form by the patients’ parents/legal representatives obtained before any study specific procedure is conducted\n- Patients must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures;\n- Patients or parents/legal representatives affiliated to the Social Security System.\n- REGISTRATION CRITERIA FOR CIC-REARRANGED SARCOMA: 1. Patients must have a histologically and molecularly confirmed diagnosis of CIC-rearranged sarcoma (either bone or soft tissue) 2. Prior treatment : no more than three prior chemotherapy regimen for metastatic disease or locally advanced for CIC-rearranged sarcoma; neo-adjuvant /maintenance therapy are not counted towards this requirement (les traitements néo- adjuvant / entretien ne sont pas pris en compte pour ce critère.) . 3. Patients with confirmed disease progression at study entry. The “baseline” radiological evaluation should demonstrate disease progression by RECIST V 1.1 when compared to a prior disease assessment done within a prior period of 3 month prior to screening 4. Patients who do not meet the inclusion/non inclusion criteria for study treatment or do not wish to participate to the therapeutic study 5. Patients who do not oppose to the collection of data (demographic data, disease characterisitics, disease related treatments, progression and survival) from their medical records."}

Exclusion criteria

• {"criterion_text":"- Prior treatment with any VEGFR inhibitor (thus, any prior exposure to sunitinib, sorafenib, pazopanib, bevacizumab, or other VEGFR inhibitor would render the patient ineligible for this study);\n- Other cancer (different histology) within 5 years prior to study treatment initiation;\n- Major surgical procedure, open biopsy, significant trauma, within the last 28 days before study treatment initiation;\n- Cardiovascular dysfunction: - Left ventricular ejection fraction (LVEF) < 50% - Congestive heart failure (New York Heart Association [NYAH]) ≥ 2 - Myocardial infarction <6 months before study - Cardiac arrhythmias requiring therapy (beta blockers or digoxin are permitted) - Uncontrolled hypertension (systolic blood pressure (SBP) > 150mmHg or diastolic blood pressure (DBP) > 90mmHg despite optimal treatment or for children/adolescents SBP and/or DBP > 95th percentile + 5 mmHg) - Unstable (angina symptoms at rest) or new-onset angina (begun within the last 3 months)\n- 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 study treatment initiation;\n- Severe hepatic impairment (Child-Pugh C);\n- Ongoing infection > Grade 2 according to NCI-CTCAE v4.0;\n- Known history of human immunodeficiency virus (HIV) infection;\n- Active hepatitis B or C or chronic hepatitis B or C requiring treatment with antiviral therapy ;\n- Prior anticancer therapy, including radiotherapy, endocrine therapy, immunotherapy, chemotherapy (CT) within the last 4 weeks (6 weeks for nitrosoureas and mitomycin C), or other investigational agents ; Concomitant antalgic palliative radiotherapy allowed;\n- Concurrent enrolment in another clinical trial in which investigational therapies are administered;\n- Known hypersensitivity to the active substance or to any of the excipients;\n- Pregnant women, women who are likely to become pregnant or are breast-feeding;\n- For adult patients, individual deprived of liberty or placed under the authority of a tutor;\n- 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;\n- Patients with history of non compliance to medical regimens or unwilling or unable to comply with the protocol\n- Interstitial lung disease with ongoing signs and symptoms at the time of informed consent\n- Non-healing wound, non-healing ulcer, or non-healing bone fracture\n- Difficulties with swallowing study tablets;\n- Patients with evidence or history of any bleeding diathesis, irrespective of severity\n- Any hemorrhage or bleeding event ≥ CTCAE Grade 3 within 4 weeks prior to the start of study medication\n- Use of biological response modifiers, such as granulocyte colony stimulating factor (G-CSF), within 3 weeks of study entry."}

Primary endpoints

• {"endpoint_text":"- The primary efficacy endpoint is the non-progression rate at 8 weeks for osteosarcoma, Ewing sarcoma and CIC-rearranged sarcoma patients, at 12 weeks for chondrosarcoma patients and at 6 months for chordoma patients. The non-progression rate will be defined as the proportion of patients without disease progression at the defined timepoint after confirmation by central radiological review (using RECIST 1.1).","definition_or_measurement_approach":"Non-progression rate defined as the proportion of patients without disease progression at the defined timepoint after confirmation by central radiological review using RECIST 1.1 (timepoint varies by tumour type: 8 weeks for osteosarcoma/Ewing/CIC-rearranged, 12 weeks for chondrosarcoma, 6 months for chordoma)."}

Secondary endpoints

• {"endpoint_text":"- Progression-Free Survival [defined using RECIST 1.1] will be measured from the date of randomization or start of treatment for cohort E until the date of radiological progression or death whatever the cause (if death occurs before progression).\n- Objective response rate [defined as complete response (CR) or partial response (PR) according to RECIST 2009, version 1.1, for all cohorts, and CHOI criteria for chordoma] ;\n- Disease control rate at 6 months (defined as the proportion of patients who a best response rating of CR, PR or stable disease [SD]), SD should be at least 8 weeks ;\n- Overall survival (defined as the time from the date of randomization or start of treatment for cohort E until the date of death due to any cause); if the patients is alive at the date of data base cut off then he will be censored at the data base cut off date;\n- Duration of response (defined as the time from date of first documented objective response of CR or PR, whichever is noted earlier, to first disease progression or death before progression ;\n- Progression-free rate at 3 and 6 months (PFR-3 and PFR-6), defined as the proportion of patients without progression at 3 and 6 months post randomization or start of treatment for cohort E;\n- Time to progression (measured from date of randomization or start of treatment for cohort E until the date of first observation of progression );\n- Growth Modulation Index (GMI) defined as ratio of time to PD under regorafenib to TTP under previous treatment. The GMI will be explored in patients receiving regorafenib after randomization or start of treatment for cohort E;\n- Identification and characterization of biomarkers\n- Toxicity according to NCI-CTC V4.0\n- Pain assessment for chordomas\n- Progression Free Survival according to CHOI criteria for chordomas All efficacy assessments using CHOI criteria (only for chordomas) will be performed by central radiological reviewers.","definition_or_measurement_approach":"Progression-Free Survival: measured using RECIST 1.1 from randomization/start of treatment to radiological progression or death. Objective response rate: CR or PR per RECIST 1.1 (CHOI criteria for chordoma). Disease control rate at 6 months: proportion with best response CR/PR/SD with SD ≥ 8 weeks. Overall survival: time from randomization/start to death (censor at database cut-off). Duration of response: time from first documented CR/PR to progression or death. PFR-3/PFR-6: proportion without progression at 3 and 6 months. Time to progression: from randomization/start to first observation of progression. GMI: ratio of time to PD under regorafenib to TTP under previous treatment. Biomarkers: identification/characterization per protocol. Toxicity: graded by NCI-CTC v4.0. CHOI-based PFS for chordomas assessed by central radiological reviewers."}

France

Earliest CTIS Part Ii Submission Date

04-04-2024

Latest Decision Or Authorization Date

09-08-2024

Processing Time Days

127

Number Of Sites

24

Number Of Participants

159

Primary sponsor

Full Name

Unicancer

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"","full_name":"BAYER HealthCare AG","duties_or_roles":"Source of monetary support","organisation_type":""}