Study of Recombinant Interleukin 21 in Combination With Sorafenib for Metastatic Renal Cell Carcinoma

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase 1/2, Open-Label, Dose Escalation Study to Assess the Safety and Pharmacokinetics of Recombinant Interleukin 21 (rIL-21) Administered Concomitantly With Sorafenib (Nexavar) in Subjects With Metastatic Renal Cell Carcinoma

Conditions
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Carcinoma, Renal Cell

Intervention / Treatment
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* Drug: rIL-21 only
* Drug: rIL-21 + sorafenib


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: rIL-21 only|Part 1: rIL-21, IV, Day 1-5 and 15-19 of each 6-week treatment course|
|Drug: rIL-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)|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety profile, including incidence and severity of adverse events |  | During treatment and 28 days after last dose of rIL-21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Carcinoma, renal cell, interleukin-21, sorafenib, Immunotherapy