Metastatic Renal Cell Carcinoma
Conditions
Keywords
Advanced, Metastatic, RCC
Brief summary
This study aims to assess the survival benefit from an early switch approach from sunitinib or pazopanib (10-12 weeks of 1st-line therapy) to nivolumab (anti-angiogenic to immunotherapy switch).
Detailed description
This is a randomized, open-label, phase II trial. Patients with advanced or metastatic renal cell carcinoma (RCC) will be randomized into two arms either receiving Nivolumab or continuation of the Tyrosin Kinase Inhibitor (TKI) treatment that they have received as 1st-line therapy. Patients must have received first line therapy with a VEGFR-TKI (Sunitinib or Pazopanib) prior to study inclusion for 10-12 weeks with documented disease control (PR/SD) according to RECIST 1.1 at time of study entry. Eligible patients will be randomized 1:1 either in the Nivolumab or in the TKI arm. Dosage of Nivolumab: 240 mg i.v. on D1 of every cycle (Q2W) for 16 weeks. After 16 weeks 480 mg i.v. on D1 of every cycle (Q4W) until disease progress, intolerable toxicity, withdrawal of consent or end of study. Dosage of Sunitinib: According to Standard of Care (SOC). Recommended dose is 50 mg p.o. once daily for 4 consecutive weeks followed by a 2-week rest period (schedule 4/2) to comprise a complete cycle of 6 weeks (until disease progress, intolerable toxicity, withdrawal of consent or end of study.). Dosage of Pazopanib: According to Standard of Care (SOC). Recommended dose is 800 mg p.o. daily continuously (until disease progress, intolerable toxicity, withdrawal of consent or end of study.).
Interventions
DRUGNivolumab
240 mg i.v. on D1 of every cycle (Q2W) for 16 weeks. After 16 weeks 480 mg i.v. on D1 of every cycle (Q4W) until disease progress, intolerable toxicity, withdrawal of consent or end of study.
DRUGSunitinib
According to Standard of Care (SOC). Recommended dose is 50 mg p.o. once daily for 4 consecutive weeks followed by a 2-week rest period (schedule 4/2) to comprise a complete cycle of 6 weeks (until disease progress, intolerable toxicity, withdrawal of consent or end of study).
DRUGPazopanib
According to Standard of Care (SOC). Recommended dose is 800 mg p.o. daily continuously (until disease progress, intolerable toxicity, withdrawal of consent or end of study).
Sponsors
Bristol-Myers Squibb
AIO-Studien-gGmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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. * 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. * Age ≥ 18 years at time of study entry * Eastern Co-operative Oncology Group (ECOG) performance status 0-2. * Metastatic or locally advanced RCC with clear cell component, not amenable to surgery with curative intention. * First-line treatment with a TKI for 10-12 weeks (limited to sunitinib or pazopanib). * Patients with measurable disease (at least one uni-dimensionally 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. * Documented partial response or stable disease to first-line TKI exposure at 10-12 weeks. * Prior therapies other than indicated in the
Exclusion criteria
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. * Adequate blood count, liver-enzymes, and renal function (obtained no later than 14 days prior to start of study treatment): White Blood Cells (WBC) ≥ 2000/μL Neutrophils ≥ 1500/μL Platelets ≥ 100 x10\^3/μL Hemoglobin \> 9.0 g/dL Serum creatinine ≤ 1.5 x Upper limit of normal (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) Aspartate Aminotransferase (AST)/Alanine Aminotransferase (ALT) ≤ 3 x ULN Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin \< 3.0 mg/dL) * Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy for 23 weeks (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of nivolumab. * Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of nivolumab * Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product. Women who are not of childbearing potential (ie, who are postmenopausal or surgically sterile as well as azoospermic) men do not require contraception.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) | 128 of events in max. 72 months | Efficacy measure |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Best overall response rate | From start of 1st line until disease progression or death of last patient (max. 72 months) | Best overall response (PR+CR) throughout the 1st-line treatment according to RECIST 1.1 |
| Progression free survival (PFS) | 72 months | PFS time of randomization to death from any caused OS From start of 1st line TKI therapy |
| Quality of Life | From randomization until disease progression or death of last patient (max. 72 months) | Health related-Quality of Life (Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI) FKSI-15 score and changes in the FKSI-15 score. |
| Safety - Absolute and relative frequencies of emergent adverse events according to CTCAE 4.03 | From randomization until 100 days after end of treatment of last patient (post last dose). | Adverse Events (AEs) / Serious Adverse Events (SAEs) / Treatment Emergent Adverse Events according to CTCAE 4.03 |
Countries
Austria, Germany
Outcome results
None listed