Metastatic Renal Cell Carcinoma MedDRA version: 21.1 Level: LLT Classification code 10050076 Term: Metastatic renal carcinoma System Organ Class: 100000004864
Conditions
Interventions
Trade Name: OPDIVO - 10 MG/ML- CONCENTRATO PER SOLUZIONE PER INFUSIONE- USO ENDOVENOSO- FLACONCINO (VETRO)- 10 ML- 1 FLACONCINO
Product Name: Opdivo
Pharmaceutical Form: Solution for infusion
INN or P
Sponsors
GRUPPO ONCOLOGICO ITALIANO DI RICERCA CLINICA (GOIRC)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -Age = 18 years on day of signing informed consent - Performance status of 0, 1 on the ECOG Performance Scale -Histologically confirmed metastatic RCC not suitable for curative-intent local therapy - Disease progressed after = 2 prior anti-angiogenic therapies - Life expectancy > 12 weeks - 2 or more measurable non-brain sites of disease based on RECIST 1.1, whose at least one potentially suitable for treatment with SBRT. In the case of a non measurable bone lesion suitable for treatment with SBRT, even only one measurable non-brain site of disease is allowed - Patients are eligible if CNS metastases are treated and patients have neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 14 days prior to enrollment. In addition, patients must either be off corticosteroids or on a stable dose or decreasing dose of = 10 mg daily prednisone (or equivalent) - Adequate organ function Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 68 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 23
Exclusion criteria
Exclusion criteria: • Prior therapy with an agent directed at PD-1, PD-L1, or PD-L2 • Currently participating in or has participated in a study of an investigational agent or using an investigational device within 2 weeks of the first dose of treatment • Any active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required systemic corticosteroids (> 10 mg daily prednisone equivalent) or immunosuppressive medications except for syndromes which would not be expected to recur in the absence of an external trigger • Any condition requiring systemic treatment with corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to first dose of study drug. Inhaled steroids and adrenal replacement steroid doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease • Active brain (CNS) metastases and/or carcinomatous meningitis • Prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., = Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier • Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., = Grade 1 or at baseline) from adverse events due to a previously administered agent. Subjects with = Grade 2 neuropathy are an exception to this criterion and may qualify for the study • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) • Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 14 days prior to the first dose of trial treatment • Any positive test for hepatitis B or hepatitis C virus indicating acute or chronic infection • Additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy • Evidence of interstitial lung disease, active non-infectious pneumonitis, or a history of grade 3 or greater pneumonitis • Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness • Live vaccine within 30 days prior to the first dose of trial treatment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate the activity of nivolumab in combination with SBRT;Secondary Objective: -evaluate the effectiveness and safety of the combination nivolumab + SBRT -to identify molecular basis of synergistic effect of stereotactic radiotherapy and Nivolumab, to identify potential resistance mechanisms, to characterize biological variables and somatic mutations that may help in optimizing the combination. ;Primary end point(s): Objective Response Rate (ORR) , as determined by investigator assessment per RECIST 1.1;Timepoint(s) of evaluation of this end point: From the date the patient entered in the study until the end of the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety assessments will include the incidence, nature, and severity of Adverse Events (AEs) and laboratory abnormalities graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v. 4.03; - to identify molecular basis of synergistic effect of stereotactic radiotherapy and immunotherapy in renal carcinomas - to identify potential resistance mechanisms - to characterize biological variables that may help in optimizing the timing and modalities of combination. - Identification of somatic mutations associated with acquired resistance to checkpoint inhibitors; Progression Free Survival (PFS); Overall Survival (OS); Objective Response Rate (ORR) of irradiated and non-irradiated metastases and duration of response, as determined by investigator assessment per RECIST 1.1.;Timepoint(s) of evaluation of this end point: from the date the patient entered in the study until the end of the study; From the date the patient entered in the study until the end of the study; time between the date of registration and the first date of documented progression, based on invesigator assessment (as per RECIST 1.1 criteria), or death due to any cause, whichever occurs first.; time between registration and the date of death from any cause; time between registration and the end of the study | — |
Countries
Italy
Contacts
Public ContactServizio Informazione sulla Sperime
Pharmaceutical Development and Services srl
Outcome results
None listed