advanced or metastatic renal cell carcinoma (RCC) MedDRA version: 21.0 Level: PT Classification code 10073251 Term: Clear cell renal cell carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10050513 Term: Metastatic renal cell carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10
Conditions
Interventions
Trade Name: Opdivo®
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Nivolumab
CAS Number: 946414-94-4
Other descriptive name: NIVOLUMAB
Concentration unit: mg/ml millig
Sponsors
AIO-Studien-gGmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent and any locally-required authorization (EU Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations. 2. Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up. 3. Age = 18 years at time of study entry 4. ECOG performance status 0-2. 5. Metastatic or locally advanced RCC with clear cell component, not amenable to surgery with curative intention. 6. First-line treatment with a TKI for 10-12 weeks (limited to sunitinib or pazopanib). 7. Patients with measurable disease (at least one unidimensionally measurable target lesion by CT-scan or MRI) according to modified Response Evaluation Criteria in Solid Tumors (RECIST 1.1). If prior palliative radiotherapy to metastatic lesions: = 1 measurable lesion that has not been irradiated. Patients with bone lesions as the only measurable lesion are eligible, provided that lesions consist of soft tissue, which is assessed via CT or MRI. 8. Documented partial response or stable disease to first-line TKI exposure at 10-12 weeks. 9. Prior therapies other than indicated in the exclusion critiria and surgeries are allowed if completed 4 weeks (for minor surgery and palliative radiotherapy for bone pain: 2 weeks) prior to start of treatment and patient recovered from toxic effects. 10. Adequate blood count, liver-enzymes, and renal function (obtained no later than 14 days prior to start of study treatment): ? WBC = 2000/µL ? Neutrophils = 1500/µL ? Platelets = 100 x103/µL ? Hemoglobin > 9.0 g/dL ? Serum creatinine = 1.5 x ULN or creatinine clearance (CrCl) = 40 mL/min (if using the Cockcroft-Gault formula below): Female CrCl = (140 - age in years) x weight in kg x 0.85/ 72 x serum creatinine in mg/dL Male CrCl = (140 - age in years) x weight in kg x 1.00/ 72 x serum creatinine in mg/dL ? AST/ALT = 3 x ULN ? Total Bilirubin = 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range 164
Exclusion criteria
Exclusion criteria: 1. Prior systemic therapy other than 10-12 weeks SOC TKI treatment for advanced or metastatic RCC. 2. Standard of care 1st-line TKI treatment for advanced or metastatic RCC for longer than 12 weeks. 3. Complete remission (CR) or progression during SOC TKI 1st- line treatment. 4. Termination of first-line treatment with TKI due to intolerance 5. Previous malignancy (other than renal cell cance cancer of the skin, pre-invasive cancer of the cervix, T1a prostate carcinoma or superficial bladder tumor [Ta, Tis and T1] are exempted. 6. Brain metastases mandating active treatment. Subjects with brain metastases are eligible if metastases have been treated and there is no magnetic resonance imaging (MRI) evidence of progression for 4 weeks after treatment is completed and within 28 days prior to the first dose of nivolumab administration. There must also be no requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration. 7. Prior therapy with anti-tumor vaccines or other immunostimulatory antitumor agents. 8. Administration of a live, attenuated vaccine within 4 weeks of start of therapy 9. Any previous treatment with an anti-PD-1, anti-PD-L1, anti- PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways 10. Subjects must have recovered from the effects of major surgery or significant traumatic injury at least 14 days before the first dose of study treatment. 11. Patients should be excluded if they have an active, known or suspected autoimmune disease. NOTE: Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger 12. Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. NOTE: Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. 13. Known chronic infection (i.e. hepatitis B or C, HIV) 14. Patients should be excluded if they have been positively tested for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection. 15. Patients should be excluded if they have a known history of testing positive for human immunodeficiency virus (HIV) or a known acquired immunodeficiency syndrome (AIDS). 16. History of severe hypersensitivity reaction to any monoclonal antibody or any constituent of the product. 17. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any subject known to have a psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent 18. Uncontrolled severe hypertension (failure of diastolic blood pressure to fall below 95 mmHg under adequate medication) 19. Curre
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the survival benefit from an early switch approach from sunitinib or pazopanib to nivolumab (anti-angiogenic to immunotherapy switch);Secondary Objective: • to compare efficacy of early switch to nivolumab vs. continuation of either sunitinib or pazopanib • to compare health-related quality of life (HR-QoL) during TKI and nivolumab treatment after early switch • to assess the influence of response to previous TKI treatment on nivolumab efficacy • to assess safety and toxicity ;Primary end point(s): overall survival;Timepoint(s) of evaluation of this end point: after death of the patient | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key Secondary Endpoint: • Best overall response (PR+CR) throughout the 1st-line treatment according to modified RECIST Additional secondary endpoints: • PFS and OS from time of randomization to death from any cause • OS rates at 24 • PFS and OS from start of 1st line TKI therapy • Duration of response • Health related-Quality of Life (Functional Assessment of Cancer Therapy-Kidney Symptom Index FKSI 15 score and changes in the FKSI 15 score) • proportion of subjects with increase from baseline in FKSI 15 (MID 3 points) • time to deterioration, measured as a composite endpoint consisting of decrease of QoL (defined by the minimal clinical relevant difference) or death (TUDD) • tumor shrinkage, i.e. relative change from baseline in sum of longest diameter • AEs / SAEs / Treatment Emergent Adverse Events according to CTCAE 4.03 ;Timepoint(s) of evaluation of this end point: - PFS and OS from time of randomization to death from any cause: after death of the patient - OS rates at 24: at 24 after study entry - AEs / SAEs / Treatment Emergent Adverse Events according to CTCAE 4.03: until up to 100 days after EOT - others: after EOT | — |
Countries
Austria, Germany
Contacts
Public ContactDr. Aysun Karatas
AIO-Studien-gGmbH
Outcome results
None listed