Clinical trial NCT03469713: Nivolumab Plus Stereotactic Body Radiotherapy in II and III Line of Patients With Metastatic Renal Cell Carcinoma
Official title: Nivolumab Plus Stereotactic Body Radiotherapy (SBRT) in II and III Line of Patients With Metastatic Renal Cell Carcinoma (mRCC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Renal Cancer Metastatic
Lead sponsor: Gruppo Oncologico Italiano di Ricerca Clinica
Sponsor class: OTHER
First posted: 2018-03-19
Enrollment: 69
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: NIVES study is an ongoing phase II, single arm, multicenter study. In this trial pts received SBRT to one non-brain measurable lesion and concomitant NIVOLUMAB, an anti-programmed cell death (PD-1). Combining SBRT with NIVO may enhance the antitumor immune responses and improve clinical outcomes, how it was demonstrated for other solid tumors with a phenomenon known as the abscopal effect . It was planned to enrolled a total of 68 pts within 12 months. The objective of the current analysis is to describe the first report of safety profile of NIVO in combination with SBRT.


Eligibility 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

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

Primary outcomes:
measure: ORR Objective Response Rate
timeFrame: 36 months from the first administration of nivolumab
Secondary outcomes:
measure: PFS Progression Free Survival
timeFrame: 36 months from the first administration of nivolumab
measure: OS Overall Survival
timeFrame: 36 months from the first administration of nivolumab
measure: ORR (Objective Response Rate) of irradiated and non-irradiated metastases and duration of response
timeFrame: 36 months from the first administration of nivolumab
measure: Incidence, nature and severity of Adverse Event (safety and tolerability)
timeFrame: 36 months from the first administration of nivolumab
Other outcomes:
measure: Analysis of expression of PD-L1
timeFrame: 36 months from the first administration of nivolumab
measure: Analysis of the genetic background of the tumor and its impact on the response to therapy
timeFrame: 36 months from the first administration of nivolumab
measure: Analysis of the immuno-modulation during therapy.
timeFrame: 36 months from the first administration of nivolumab
measure: Identification of somatic mutations associated with acquired resistance to checkpoint inhibitors
timeFrame: 36 months from the first administration of nivolumab
Locations:
city: Reggio Emilia
country: Italy
facility: Struttura Complessa di OncologiaIRCCS- Istituto in Tecnologie Avanzate e Modelli Assistenziali in Oncologia Arcispedale Santa Maria Nuova
Study officials:
affiliation: Gruppo Oncologico Italiano di Ricerca Clinica
name: Carmine Pinto, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Maia MC, Salgia M, Pal SK. Harnessing cell-free DNA: plasma circulating tumour DNA for liquid biopsy in genitourinary cancers. Nat Rev Urol. 2020 May;17(5):271-291. doi: 10.1038/s41585-020-0297-9. Epub 2020 Mar 17.