Soft tissue sarcoma (undifferentiated pleomorphic sarcoma, synovial sarcoma, alveolar soft part sarcoma, clear cell sarcoma, angiosarcoma, epithelioid hemangiosarcoma, solitary fibrous tumor and epithelioid sarcomas) or bone sarcoma (osteosarcoma/high grade bone sarcoma, Ewing sarcoma, or dedifferentiated chondrosarcoma), with metastatic/advanced and measurable disease.
Conditions
Interventions
Trade Name: Sutent
Product Name: Sunitinib
Product Code: LO1XE04
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: SUNITINIB
CAS Number: 557795-19-4
Concentration unit: mg milligram(s)
Concentra
Sponsors
Grupo Español de Investigación en Sarcomas (GEIS)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients must provide written informed consent prior to performance of study-specific procedures and must be willing to comply with treatment and follow-up. Informed consent must be obtained prior to start of the screening process. Procedures conducted as part of the patient’s routine clinical management (e.g. blood count, imaging tests, etc.) and obtained prior to signature of informed consent may be used for screening or baseline purposes as long as these procedures are conducted as specified in the protocol. 2. Age: 18-80 years. 3. Histologic diagnosis of soft tissue sarcoma (undifferentiated pleomorphic sarcoma, synovial sarcoma, alveolar soft part sarcoma, clear cell sarcoma, angiosarcoma, epithelioid hemangiosarcoma, solitary fibrous tumor and epithelioid sarcomas) or bone sarcoma (osteosarcoma/high grade bone sarcoma, Ewing sarcoma or dedifferentiated chondrosarcoma) confirmed by central pathology review. Mandatory paraffin embedded tumor blocks must be provided for all subjects without exception for biomarker analysis before treatment (first biopsy) and at end of month 3 or earlier (second biopsy). 4. Metastatic/advanced disease in progression in the last 6 months. 5. Patients have previously received at least anthracyclines. 6. Measurable disease according to RECIST 1.1 criteria. 7. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1. 8. Adequate hepatic, renal, cardiac, and hematologic function. 9. Laboratory tests as follows: - Absolute neutrophil count = 1,200/mm³ - Platelet count = 100,000/mm³ - Bilirubin = 1.5 mg/dL - PT and INR = 1.5 - AST and ALT = 2.5 times upper limit of normal - Creatinine = 1.5 mg/dL - Calcium = 12 mg/dL - Blood glucose =65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: 1. Three or more previous lines of chemotherapy for the advanced disease. 2. Previous antiangiogenic agent, anti-programmed death-1 (PD-1), anti-programmed death-ligand 1 (PD-L1), anti PD-L2 or anti CTLA-4 antibody. 3. Prior immune-related adverse event (Grade 3 or higher immune-related pneumonitis, hepatitis, colitis, endocrinopathy) with prior immunotherapy (e.g. cancer vaccine, cytokine, etc.). 4. Active, known or suspected autoimmune disease. 5. A condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. 6. Uncontrolled intercurrent illness including (not limited to): symptomatic congestive heart failure (CHF) (New York Heart Association [NYHA] III/IV), unstable angina pectoris or coronary angioplasty, or stenting within 24 weeks prior to registration, unstable cardiac arrhythmia (ongoing cardiac dysrhythmias of NCI CTCAE version 4.0 Grade >= 2), known psychiatric illness that would limit study compliance, intra-cardiac defibrillators, known cardiac metastases, or abnormal cardiac valve morphology (>= Grade 3). 7. Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection. 8. Other disease or illness within the past 6 months, including any of the following: - Myocardial infarction - Severe or unstable angina - Coronary or peripheral artery bypass graft - Symptomatic congestive heart failure - Cerebrovascular accident or transient ischemic attack - Pulmonary embolism 9. Evidence of a bleeding diathesis. 10. Ongoing cardiac dysrhythmias > Grade 2. 11. Uncontrolled hypertension, defined as blood pressure > 150/100 mm Hg despite optimal medical therapy. 12. Psychiatric illness or social situation that would preclude study compliance. 13. Pre-existing thyroid abnormality, defined as abnormal thyroid function tests despite medication. 14. Prolonged QTc interval (i.e., QTc > 450 msec for males or QTc > 470 msec for females) on baseline ECG. 15. Hemorrhage = Grade 3 in the past 4 weeks. 16. History of allergy to study drug components.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of the sunitinib plus nivolumab combination as measured by the progression-free survival rate (PFSR) at 6 months in patientswith advanced soft tissue and bone sarcomas.;Secondary Objective: - To evaluate overall survival (OS). - To determine the objective response rate (ORR). - To evaluate efficacy according to immune-related response. - To evaluate efficacy according to Choi response. - To evaluate the safety profile according to CTCAE 4.0. - To evaluate the outcome of post protocol treatments.;Primary end point(s): Progression-free survival rate (PFSR): Efficacy measured by the PFSR at 6 months according to RECIST 1.1. PFSR at 6 months is defined as the percentage of patients who did not experience progression or death due to any cause since the first dose of experimental treatment until month 6 after treatment initiation.;Timepoint(s) of evaluation of this end point: At 6 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Overall survival (OS): OS is defined as the time between the date of first dose and the date of death due to any cause. OS will be censored on the last date a subject was known to be alive. - Objective Response Rate (ORR): ORR is defined as the number of subjects with a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) divided by the number of response evaluable subjects (according to RECIST 1.1 criteria). - Efficacy measured through immune-related response criteria. - Efficacy measured through tumor response according to Choi criteria. The evaluation criteria will be based on the identification of target lesions in baseline and their follow-up until tumor progression. - Safety profile of the experimental treatment, through assessment of adverse event type, incidence, severity, time of appearance, related causes, as well as physical explorations and laboratory tests. Toxicity will be graded and tabulated by using CTCAE 4.0. - Clinical outcomes of post protocol treatments assessed by observation of such treatments in follow-up stage.;Timepoint(s) of evaluation of this end point: - Overall survival (OS): At 2 years - Objective Response Rate (ORR): Every 3 months - Efficacy measured through immune-related response criteria: At the end of treatment - Efficacy measured through tumor response according to Choi criteria: Every 3 months - Safety profile: At the end of treatment - Clinical outcomes: During follow-up | — |
Countries
Spain
Contacts
Public ContactClinical Trials
Sofpromed Investigación Clínica SLU
Outcome results
None listed