Phase III Sequential Open-label Study to Evaluate the Efficacy and Safety of Sorafenib Followed by Pazopanib Versus Pazopanib Followed by Sorafenib in the Treatment of Advanced / Metastatic Renal Cell Carcinoma (SWITCH-II)
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.
|Renal Cell Carcinoma||Drug: Sorafenib+Pazopanib Drug: Pazopanib+Sorafenib||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Phase III Randomized Sequential Open-label Study to Evaluate the Efficacy and Safety of Sorafenib Followed by Pazopanib Versus Pazopanib Followed by Sorafenib in the Treatment of Advanced / Metastatic Renal Cell Carcinoma|
- 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. [ Time Frame: 4 years ]
- Time from randomization to progression during second-line therapy (total TTP) [ Time Frame: 1 year ]
- Time to first-line treatment failure (progression, death, discontinuation due to toxicity) descriptively in each arm [ Time Frame: 1 year ]
- PFS in first-line and second-line treatment, descriptively [ Time Frame: 4 years ]
- Overall survival, descriptively (data cut-off same as for primary endpoint [ Time Frame: 4 years ]
- Disease Control Rate (DCR); Response rates in first-line and in second-line (CR, PR, SD according to RECIST criteria) [ Time Frame: 4 years ]
- Health-related Quality of Life (FACIT-F, FKSI-10) [ Time Frame: 4 years ]
- Biomarker programme [ Time Frame: 4 years ]Circulating tumor cells, Single Nucleotide Polymorphisms, Serum Protein Signatures
- Safety and tolerability [ Time Frame: 4 years ]Monitoring of adverse events, summaries and listings of adverse events
|Study Start Date:||May 2012|
|Primary Completion Date:||October 30, 2016 (Final data collection date for primary outcome measure)|
Experimental: Sorafenib followed by pazopanib
Sorafenib 400 mg bid orally until progression or intolerable toxicity, followed by pazopanib 800 mg once daily orally until progression or intolerable toxicity.
During first- and second-line, treatment visits are scheduled in weeks 0,2,4,8,12, and every 4 weeks thereafter, with tumor assessments and electrocardiogram after every second cycle (every 8 weeks).
Sorafenib (first-line) followed by Pazopanib (second-line)
Experimental: Pazopanib followed by Sorafenib
Pazopanib 800 mg once daily orally until progression or intolerable toxicity, followed by Sorafenib 400 mg bid orally until progression or intolerable toxicity:
During first- and second-line, treatment visits are scheduled in weeks, 0,2,4,8,12, and every 4 weeks thereafter, with tumor assessments and electrocardiogram after every second cycle (every 8 weeks).
Pazopanib (first-line) followed by Sorafenib (second-line)
Please refer to this study by its ClinicalTrials.gov identifier: NCT01613846
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|Principal Investigator:||Jürgen E. Gschwend, Prof.||Klinikum rechts der Isar, TU München|