Renal cell carcinoma stage IV MedDRA version: 8.1 Level: LLT Classification code 10038414
Conditions
Interventions
Product Name: rIL-21
Pharmaceutical Form: Solution for injection
CAS Number: 716840-32-3
Current Sponsor code: NN028
Other descriptive name: rIL-21
Concentration unit: mg/ml milligram(s)/millilitre
Co
Sponsors
Novo Nordisk A/S
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Informed consent obtained before any trial-related activities. (Trial-related activities are any procedure that would not have been performed during normal management of the subject.) 2.Histologically verified and surgically incurable stage IV RCC of clear cell type. (clear cell type only required for phase 2a) 3.18 years of age or above 4.ECOG performance status of 0 or 1. Please refer to Appendix F. 5.Life expectancy of at least 3 months 6.0-2 risk factors according to Motzer criteria (favourable or intermediate risk) (1). Please be referred to Appendix D. 7.Prior resection of the primary tumour required 8.Full recovery from surgery for stage IV disease 9.Remaining measurable disease (according to RECIST) required for phase 2a only. Haematopoietic parameters: 10.White blood cell (WBC) higher/equal than 2.5 x 10 superscript 9/L 11.Absolute neutrophil count (ANC) higher/equal than 1.5 x 10 superscript 9/L 12.Platelet count higher/equal than 100 x 10 superscript 9/L 13.Haemoglobin higher/equal than 6.2 mmol/L 14.No signs of haemolytic anaemia 15.Serum creatinine less/equal than 177 µmol/L Hepatic parameters: 16.Bilirubin less/equal than 1.25 x upper limit of normal (ULN) 17.AST/SGOT less/equal than 2.5 x ULN 18.LDH less/equal than 2x upper limit of normal 19.Negative serologic testing for Hepatitis B and C 20. ALT = 2.5 x ULN 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 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1.Previous systemic treatment for stage IV disease 2.Rare histological subtypes of RCC (true papillary, collecting duct, sarcomatoid features) applies for phase 2a only 3.History of or active presence of auto-immune diseases (except vitiligo and treated pernicious anaemia) 4.History of any other active malignancy (except basal cell carcinoma of the skin and cervical cancer in situ) within five years prior to enrolment 5.Known chronic infectious disease including human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS) related illness 6.Any significant systemic disease which according to the Investigator could compromise the safety of the subject or interfere with the trial objectives 7.Concurrent treatment with systemic corticosteroids (topical or inhaled corticosteroid treatment is permitted) 8.Known or suspected allergy to trial products or related products 9.Previous participation in this trial (re-screening is allowed when agreed with the Local Trial Manager or the International Trial Manager) 10.Pregnant, breast-feeding, or the intention of becoming pregnant or not using adequate contraceptive measures (including country-specific adequate measures, if any). In Germany adequate contraception is: implants, injectables, combined oral contraceptives, hormonal IUD, sexual abstinence, or vasectomised partner. No specific requirements in the Netherlands. 11.The receipt of any investigational drug within 3 months prior to start on this trial (day 1) 12.The receipt of concomitant anti-coagulation therapy Low Molecular Weight (LMW) heparins allowed). 13.Cerebrovascular accident or transient ischemic attack within the last 12 months 14.Deep venous thrombosis or pulmonary embolism within the last 12 months Cardiac events within the last 12 months, such as: 15.Myocardial infarction 16.Severe/unstable angina 17.Coronary/peripheral artery bypass graft 18.Symptomatic congestive heart failure (CHF) Radiotherepy: 19. Radiotherapy within the last 4 weeks prior to start of treatment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase 1: To assess the safety and tolerability of increasing doses of recombinant human Interleukin-21 (rIL-21), administered s.c. in a thrice weekly regimen, in combination with sunitinib 50 mg once daily (OD) p.o. administered according to manufacturer’s instructions (“4 weeks on 2 weeks off” schedule); to determine the maximum tolerated dose (MTD) in subjects with stage IV renal cell carcinoma (RCC). Phase 2a: To estimate the response rate of s.c. rIL-21 and sunitinib in combination, with reference to sunitinib alone, measured according to RECIST in subjects with stage IV RCC. ;Secondary Objective: Phase 1: to: -describe the pharmacokinetic responses in subjects treated with this regimen (rIL-21 and sunitinib).-assess if antibodies against recombinant human IL-21 are induced during therapy.-describe the pharmacodynamic responses in subjects treated with this regimen.-measure effects of this treatment regimen on tumour size according to Response Evaluation Criteria In Solid Tumours (RECIST) (if applicable). Phase 2a: to:-compare the safety profile of the combination treatment with that of sunitinib alone in terms of frequency of adverse events (incidence and severity).-describe the pharmacokinetic response in subjects treated with these regimens at steady state (rIL-21 and sunitinib).-describe the pharmacodynamic responses in subjects treated with these regimens.-estimate progression free survival in both treatment arms.-describe Health Related Quality of Life in both treatment arms.-assess if antibodies against recombinant human IL-21 are induced during therapy with rIL-21. ;Primary end point(s): Phase 1: The primary endpoint for safety is observed toxicity to the combination of rIL-21 and sunitinib assessed using the US National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. DLT and MTD will be determined according to the criteria described in Section 11.11. Phase 2a: The primary endpoint for tumour response | — |
Countries
Denmark, Germany, Netherlands
Outcome results
None listed