kidney cancer
Conditions
Interventions
All patients will be continuously treated with a fixed dose of sorafenib, 400
mg bid. If after 4 weeks of sorafenib treatment (run-in period), patients have
no signs of progressive disease and toler
Sponsors
NKI-AVL
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: - Patients with cytologically or histologically proven RCC, clear cell subtype, with documented progressive disease either after first line, interferon(IFN)-a- or interleukin-2-based therapy or for whom IFN-a-based treatment is not considered appropriate because of prognostic features according to Motzer. - Evaluable and measurable disease (according to RECIST criteria) - PF 0-1 - Adequate bone marrow, hepatic and renal function - life expectancy of at least 3 months - age of 18 or older - willingness to use a medically approved method of contraception - before patient randomization, written informed consent must be given and documented to ICH/EU GCP, and national/local regulatory requirements and the local rules followed in the institution
Exclusion criteria
Exclusion criteria: - Uncontrolled or poorly controlled hypertension (systolic blood pressure >= 150 mmHg, diastolic blood pressure >= 90 mmHg). Initiation or adjustment of blood pressure medications is permitted prior to study treatment provided that 3 consecutive blood pressure readings are
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Only patients who start concurrent IL-2 treatment are evaluable for this study. If treatment with sorafenib during the first 4 weeks has to be stopped, interrupted or adjusted because of dose-limiting toxicity (DLT) (see for definition of DLT below) or other reasons, patients will go off-study and will be replaced. In these cases, patients are allowed to continue treatment with sorafenib according to the treating physician*s opinion. Adverse events that are encountered during the first cycle when IL-2 is co-administered (6 weeks) will be used to guide dose escalation and to define the MTD. Adverse events will be graded according to the NCI-CTC version 3.0. Dose-limiting toxicity (DLT) will be defined as those adverse advents that are considered possibly, probably, or definitely related to the study drugs. DLT is defined as: - grade 4 neutropenia or grade 4 thrombopenia - grade 3 or greater non-hematologic adverse events except fever, rigor/chills, renal dysfunction, hypertension, nausea/vomiting, diarrhea, and fatigue for which the following criteria will apply: o fever or rigor/chills of any grade will not be considered DLT o creatinine >= 2 x ULN o hypertension with systolic blood pressure >= 160 mmHg and/or diastolic blood pressure >= 100 mmHg lasting longer than 14 days despite adequate treatment o grade 3 or greater persistent (more than 7 days) nausea/vomiting despite adequate treatment or prophylaxis o grade 3 or greater (more than 7 days) diarrhea despite adequate treatment or prophylaxis o grade 4 fatigue At each dose level, at least 3 patients will be treated. Patients in each dose level will be treated for 4 weeks with sorafenib (400 mg bid) (run-in period). After this, IL-2 will be administered at the designated dose for that dose level. When each patient of the first three entered patients in a particular dose level has had 6 weeks of treatment with the combination of sorafenib and IL-2 without a DLT, the IL-2 dose will be | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetics: To assess whether concurrently administered IL-2 affects pharmacokinetics of sorafenib, systemic blood levels of sorafenib will be determined at the end of the run-in period at day 29 prior to the first administration of IL-2 alone when sorafenib is given as single agent and at day 5 after starting IL-2 sc. Per time point 20 ml will be sampled. Cytokines: To assess the effects of sorafenib as well as of the combination of sorafenib and IL2 on VEGF and interleukin-6 (IL-6) levels in the peripheral circulation, 20 ml peripheral blood (serum) will be sampled at: Base-line, day 29 run-in period prior to the first administration of IL-2, day 5 after start concomitant IL-2, day 43 after start concomitant IL-2. Peripheral blood cells: To assess the effects of sorafenib as well as of the combination of sorafenib and IL2 on peripheral blood cells (NK-cells (CD56+, CD3-), Cytotoxic T-cells (CD3+, CD8+), T-helper cells (CD3+, CD4+), Regulatory T-cells (CD3+, CD4+, CD25bright/Foxp3)), 30 ml blood (EDTA/heparin) will be sampled at: Base-line, day 29 run-in period prior to the first administration of IL-2, day 5 after start concomitant IL-2, day 42 after start concomitant IL-2. | — |
Countries
Netherlands
Outcome results
None listed