Carcinoma, Renal Cell
Conditions
Keywords
Carcinoma, renal cell, interleukin-21, sorafenib, Immunotherapy
Brief summary
The purpose of the study is to evaluate whether recombinant IL-21 used in combination with sorafenib is safe for patients with metastatic renal cell carcinoma (RCC).
Detailed description
This is a Phase 1/2 open-label dose-escalation study of rIL-21 given in combination with sorafenib to patients with metastatic RCC. The Phase 1 part of this study will estimate the maximum tolerated dose of rIL-21 given for 1 treatment course (consisting of two 5-day cycles of rIL-21) in combination with a standard dose of sorafenib administered during a 6-week treatment course. Increasing doses of rIL-21 will be studied sequentially in different groups of patients. The Phase 2 part of the study will further evaluate the safety and preliminary antitumor activity of rIL-21 at the dose recommended from Phase 1 in combination with sorafenib. Patients will be evaluated for safety over the course of the study. Disease evaluation (tumor restaging) will be performed during the last week of each 6-week treatment course. Patients with stable disease or better at this evaluation may go on to receive additional treatment courses. Patients may be in the study for 2 to 7 months.
Interventions
DRUGrIL-21 only
Part 1: rIL-21, IV, Day 1-5 and 15-19 of each 6-week treatment course
DRUGrIL-21 + sorafenib
Part 2: rIL-21 IV, Day 1-5 and 15-19 of each 6-week treatment course + sorafenib (up to 400 mg taken orally twice daily)
Sponsors
ZymoGenetics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of RCC of predominantly clear cell histology * Either no prior treatment or a maximum of 2 prior treatment regimens for metastatic RCC that included no more than 1 treatment regimen targeting the vascular endothelial growth factor (VEGF) pathway (Phase 1 only) * At least 1 but no more than 2 prior systemic therapies for metastatic RCC that included no more than 1 therapy targeting the VEGF pathway (Phase 2 only) * Disease measurable per the Response Evaluation Criteria in Solid Tumors (RECIST) (Phase 2 only)
Exclusion criteria
* Presence of acute infection or other significant systemic illness * Central nervous system involvement by malignancy * History of other cancer within 5 years * Previously received rIL-21 or sorafenib
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety profile, including incidence and severity of adverse events | During treatment and 28 days after last dose of rIL-21 |
Secondary
| Measure | Time frame |
|---|---|
| Objective response rate at recommended dose of rIL-21 | Every 6 weeks during treatment and then every 3 months after last dose of rIL-21 until 3 months after median survival is reached |
| Progression-free survival at recommended dose of rIL-21 | Every 6 weeks during treatment and then every 3 months after last dose of rIL-21 until 3 months after median survival is reached |
| Pharmacokinetic profiles of rIL-21 and sorafenib | rIL-21: During treatment and 15 days after dosing; sorafenib: During treatment and 22 days after dosing |
Countries
United States
Outcome results
None listed