Renal Cell Carcinoma
Conditions
Brief summary
Sorafenib and pazopanib are both effective and promising treatments for advanced Renal Cell Carcinoma (RCC). Both drugs are registered for this indication. No prospective comparative data in advanced RCC (or other indications) have been published. A search in the clinicaltrials.gov database did not reveal any planned or ongoing studies. As sequential therapy is now the standard of treatment for advanced RCC it is important to evaluate in clinical trials what the value of different sequential strategies is. This needs to be done every time new agents are introduced into the treatment armamentarium. As there are no data yet on the sequential use of sorafenib followed by pazopanib or vice versa, this sequence, however, will most certainly be used in daily practice, it is required to examine efficacy and safety of this sequential approach in a clinical trial in a randomized setting. Therefore, the investigators have designed an open randomized study in patients not previously treated for advanced RCC. Suitable patients will be randomized (1:1) in 2 groups.
Interventions
DRUGSorafenib+Pazopanib
Sorafenib (first-line) followed by Pazopanib (second-line)
DRUGPazopanib+Sorafenib
Pazopanib (first-line) followed by Sorafenib (second-line)
Sponsors
Technical University of Munich
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Patients with metastatic / advanced RCC (all histologies), who are not suitable for cytokine therapy and for whom study medication constitutes first-line treatment. For cytokine- unsuitability at least one of the following criteria must be fulfilled\*: * Age 66 to 88 years * Non-clear cell histology RCC * Intermediate risk according to MSKCC score * ECOG ≥ 1 and\> 1 organ metastasis + \< 24 months between diagnosis and establishing indication for interleukin-2-therapy * ECOG ≥ 1 and unable to carry on normal activity or do active work (Karnofsky Index 70%) * Creatinine ≥ 1x ULN and \< 2x ULN * Total bilirubin ≥ 1x ULN and \< 1.5x ULN * Present autoimmune disease * Patients who might require steroids * Hypersensitivity against cytokines * Severe organic disease, not interfering with other in-/
Exclusion criteria
of the Switch-2 study * Non-symptomatic brain metastases * Severe lung disease (e.g. PAH, COPD) with Pa O2 \< 60 mmHg on rest 2. Age ≥ 18 and ≤ 85 years 3. Karnofsky Index ≥ 70% (see appendix 15.1) 4. MSKCC prognostic score (2004), low or intermediate (see appendix 15.2) 5. Life expectancy of at least 12 weeks 6. Subjects with at least one uni-dimensional (for RECIST 1.1) measurable lesion. Lesions must be measured by CT/MRI- scan 7. Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to start of therapy: * hemoglobin \> 9.0 g/dl * absolute neutrophil count (ANC) \> 1,500 µl * Platelet count ≥ 100,000 / µl * total bilirubin \< 1.5x the upper limit of normal (Note: Subjects with Gilbert' Syndrome are eligible if their total bilirubin is \< 3.0 X ULN and direct bilirubin ≤ 35 %). * ALAT and ASAT \< 2.5x upper limit of normal (Note: concomitant elevations in bilirubin ans ASAT/ALAT above 1.0x upper limit of normal are not permitted). * Alkaline phosphatase \< 4x upper limit of normal * PT-INR/aPTT \< 1.2x upper limit of normal (Patients who are being therapeutically anticoagulated with an agent such as coumadin or heparin will be allowed to participate provided that their INR is stable and within the recommended range for the desired level of anticoagulation and no prior evidence of underlying abnormality in these parameters exists). * Serum creatinine \< 2x upper limit of normal 8. Written Informed Consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate if progression-free survival from randomization to progression or death during second-line therapy (Total PFS) of sorafenib followed by pazopanib is non-inferior compared to pazopanib followed by sorafenib. | 4 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time from randomization to progression during second-line therapy (total TTP) | 1 year | — |
| PFS in first-line and second-line treatment, descriptively | 4 years | — |
| Overall survival, descriptively (data cut-off same as for primary endpoint | 4 years | — |
| Time to first-line treatment failure (progression, death, discontinuation due to toxicity) descriptively in each arm | 1 year | — |
| Health-related Quality of Life (FACIT-F, FKSI-10) | 4 years | — |
| Biomarker programme | 4 years | Circulating tumor cells, Single Nucleotide Polymorphisms, Serum Protein Signatures |
| Safety and tolerability | 4 years | Monitoring of adverse events, summaries and listings of adverse events |
| Disease Control Rate (DCR); Response rates in first-line and in second-line (CR, PR, SD according to RECIST criteria) | 4 years | — |
Countries
Austria, Germany, Netherlands
Outcome results
None listed