Patients aged 12 years or older with unresectable locally advanced or metastatic osteosarcoma or Ewing sarcoma MedDRA version: 17.1 Level: PT Classification code 10031291 Term: Osteosarcoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 17.1 Level: LLT Classification code 10015563 Term: Ewing's sarcoma NOS System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Cometriq
Product Name: cabozantinib
Product Code: XL 184
Pharmaceutical Form: Tablet
INN or Proposed INN: cabozantinib
CAS Number: 849217-68-1
Current Sponsor code: XL-184
Other descriptiv
Sponsors
Institut Bergonié
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients must have histologically confirmed diagnosis of osteosarcoma or Ewing sarcoma by central review, except if the diagnosis was already confirmed by the RRePS (Réseau de Référence en Pathologie des Sarcomes et des Tissus Mous et des Viscères) network. 2. Relapsed disease after standard chemotherapy. 3. Patients must have measurable disease (outside any previously irradiated field) defined as per RECIST v1.1 with at least one lesion that can be measured in at least one dimension (longest diameter to be recorded) as > 10 mm with spiral CT scan. 4. Age =12 years. 5. ECOG performance status =1 (see Appendix A). 6. Life expectancy of greater than 3 months. 7. Patients must have normal organ and marrow function as defined below: - absolute neutrophil count =1,500/mcL - platelets =100,000/mcL - total bilirubin =1.5 × ULN - AST(SGOT)/ALT(SGPT) =3.0 × institutional upper limit of normal - creatinin =1.5 × ULN OR creatinine clearance =50 mL/min/1.73 m² for patients with creatinine levels above institutional normal (Cockcroft formula, see Appendix I). - hemoglobin =9 g/dL - serum albumin =2.8g/dL - lipase <2.0 × ULN and no radiologic or clinical evidence of pancreatitis - urine protein/creatinine, ratio (UPCR) =1 - serum phosphorus, calcium, magnesium, and potassium = LLN 8. Female subjects of childbearing potential must not be pregnant at screening. Females of childbearing potential are defined as premenopausal females capable of becoming pregnant (ie, females who have had any evidence of menses in the past 12 months, with the exception of those who had prior hysterectomy). However, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, low body weight, ovarian suppression or other reasons. 9. The effects of Cabozantinib on the developing human fetus are unknown. For this reason and because tyrosine kinase inhibitors agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (see below) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of Cabozantinib administration. Sexually active subjects (men and women) must agree to use medically accepted barrier methods of contraception (e.g., male or female condom) during the course of the study and for 4 months after the last dose of study drug(s), even if oral contraceptives are also used. All subjects of reproductive potential must agree to use both a barrier method and a second method of birth control during the course of the study and for 4 months after the last dose of study drug(s). 10. Metastatic or unresectable locally advanced. 11. Documented disease progression (as per RECIST v1.1) before study entry. For patients with osteosarcoma, this progression will be confirmed by central review on the basis of two CT scan or MRI obtained at less than 6 months in the period of 12 months prior to inclusion. 12. Ability to understand and the willingness to sign a written informed consent docum
Exclusion criteria
Exclusion criteria: 1.cytotoxic chemotherapy or biologic agents within 3 weeks, or nitrosoureas/ mitomycin C within 6 weeks before the first dose of study treatment 2.Prior treatment with Cabozantinib 3.Radiation therapy for bone metastasis within 2 weeks, any other external radiation therapy within 4 weeks before the first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before the first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible 4.Small molecule kinase inhibitor within 14 days before the first dose of study treatment 5.Any other type of investigational agent within 28 days before the first dose of study treatment 6.Subject has not recovered to baseline or CTCAE =Grade 1 from toxicity due to all prior therapies except alopecia and other non-clinically significant AEs 7.Primary brain tumor 8.Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery and stable for at least 2 weeks before the first dose of study treatment 9.Subject has PT/INR or PTT test =1.3 x the laboratory ULN within 7 days before the first dose of study treatment 10.Subject requires concomitant treatment, in therapeutic doses, with anticoagulants, or antiplatelet agents.Low dose aspirin, low-dose warfarin, and prophylactic low molecular weight heparin are permitted 11.Subject requires chronic concomitant treatment of strong CYP3A4 inducers 12.Subject has experienced any of the following:•clinically-significant gastrointestinal bleeding within 6 months before the first dose of study treatment•hemoptysis of =0.5 teaspoon or any other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment 13.Subject has radiographic evidence of cavitating pulmonary lesion(s) 14.Subject has tumor in contact with, invading or encasing any major blood vessels 15.Subject has evidence of tumor invading the GI tract, or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib 16.Subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions 1.Cardiovascular disorders including:a)Congestive heart failure : New York Heart Association Class III or Class IV b)Concurrent uncontrolled hypertension despite optimal antihypertensive treatment within 7 days of the first dose of study treatment c)History of congenital long QT syndrome d)Any of the following within 6 months before the first dose of study treatment:•unstable angina pectoris•clinically-significant cardiac arrhythmias•stroke•myocardial infarction•thromboembolic event requiring therapeutic anticoagulation 2.Gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including a)Any of the following within 28 days before the first dose of study treatment •intra-abdominal tumor/metastases invading GI mucosa•any evidence of active peptic ulcer disease•any evidence of inflammatory bowel disease diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis•malabsorption syndrome b)Any of the following within 6 months before the first dose of study treatment:•abdominal fistula•gastrointestinal perforation•bowel or gastric outlet obstruction•intra-abdominal abscess. 3.Other disorders associated with a high risk of fistula formation including PEG tube placement wit
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the antitumor activity of cabozantinib in terms of : •Osteosarcoma: 6-month non-progression (Complete response, partial response and stable disease) and 6-month objective response (Complete response, partial response) rates (composite endpoint) as per the Response Evaluation Criteria in Solid Tumors, Revised RECIST v1.1. •Ewing sarcoma: 6-month objective response as per the revised RECIST v1.1. ;Secondary Objective: •Ewing sarcoma only: 6-month non-progression rate Both strata: •Best overall response (as per the revised RECIST v1.1); •1- and 2-year progression-free survival; •1- and 2-year overall survival; •Cabozantinib safety; •To assess the ability of metabolic tumor response as measured by FDG-PET at the end of one cycle of treatment to predict PFS. ;Primary end point(s): Efficacy will be evaluated based on 6-month non-progression and 6-month objective response (composite primary endpoint) for osteosarcoma and 6-month objective response rate (ORR - primary endpoint) for Ewing sarcoma. Primary endpoint efficacy analyses will be based on radiological data reviewed by an independent expert radiologist.;Timepoint(s) of evaluation of this end point: 6 months after the beginning of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints include 6-month ORR for Ewing sarcoma, as well as for both strata: best overall response, 1- and 2-year PFS, and 1- and 2-year OS.;Timepoint(s) of evaluation of this end point: 6-month ORR : 6 months after the beginning of treatment Best overall response : assessed as long as patients is under treatment 1-year PFS and 1-year OS : assessed one year post treatment initiation 2-year PFS and 2-year OS : assessed two yearrs post treatment initiation. | — |
Countries
France
Contacts
Public ContactDeputy General Manager
INSTITUT BERGONIE
Outcome results
None listed