NCT00732914

Sequential Study to Treat Renal Cell Carcinoma

A Phase III Randomized Sequential Open-Label Study to Evaluate the Efficacy and Safety of Sorafenib Followed by Sunitinib Versus Sunitinib Followed by Sorafenib in the Treatment of First-Line Advanced / Metastatic Renal Cell Carcinoma

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 272 (actual)
• Sponsor: Sponsor GmbH · Academic / Other
• Sex: All
• Age: 18 Years – 85 Years
• Healthy volunteers: Not accepted

Summary

Primary: To evaluate if progression-free survival from first treatment to progression or death during second-line therapy (total PFS) of sorafenib followed by sunitinib is superior compared to sunitinib followed by sorafenib. Secondary: 1. Time from first treatment to progression during second-line therapy (total TTP) 2. Time to first-line treatment failure (progression, death, discontinuation due to toxicity) descriptively in each arm 3. PFS in first-line and second-line treatment, descriptively 4. Overall survival, descriptively (data cut-off same as for primary endpoint) 5. Disease Control Rate (DCR); Response rates in first-line and in second-line (CR, PR, SD according to RECIST criteria) 6. Cardiotoxicity analysis by means of echocardiography and NT-pro BNP with an interim analysis after 100 patients of each arm have completed the study 7. Safety and tolerability

Detailed description

The results of three sequential retrospective studies (Sablin et al, ASCO 2007; Dham et al, ASCO 2007; and Tamaskar et al, 2008) support the sequential administration of sorafenib and sunitinib even though these two drugs have an overlap of targets. These results suggest the lack of cross resistance between sorafenib and sunitinib. This study is a sequential, randomized, open-label (1:1), multicenter phase III study starting in first-line of metastatic / advanced RCC using in the experimental arm sorafenib until progression followed by sunitinib and in the control arm sunitinib until progression followed by sorafenib. Sorafenib-patients will switch to sunitinib and vice versa, with a treatment-free period of at least one and up to maximum four weeks after confirmed first-line treatment failure, in order to avoid additive toxicity. In general, the first-line treatment should be continued until progression (RECIST). However, if patients do not tolerate the first-line medication (sorafenib or sunitinib) because of toxicity, they may cross-over to the second-line therapy (sunitinib or sorafenib) despite the lack of progression, if an appropriate attempt according to a specific dose reduction / interruption scheme has been made to cope with the toxicity and try to resume first line therapy, if deemed appropriate with a reduced dose. In case of discontinuation of first-line treatment because of toxicity, patients will be enrolled for the second-line treatment, only after nonhematological toxicity has resolved to grade ≤1 and hematological toxicity to grade ≤2. As an exception, patients who refuse to be treated further with the first-line regimen due to intolerability despite having no progression may be crossed over to the second-line treatment, if they consent and are in general compliance. Any crossover, also without progression, requires a CT scan, which is in this case also considered the baseline scan for the second-line treatment. One cycle is of six weeks duration. Patients will undergo a CT/MRI scan after every second cycle (i.e. after 12 weeks each), which will be evaluated according to RECIST criteria. There will be no continuation of the same study medication beyond progression in both first- or second-line therapy. After the study reached its primary endpoint cut off, i.e. after 194 endpoint events have occurred, clean data for these patients exist and a statistical analysis has been performed data collection will be stopped. After that the trial is terminated and a close out visit will be performed. Remaining patients will be treated outside the study and will be censored in the analysis.

Conditions

• Renal Cell Carcinoma

Interventions

Type	Name	Description
DRUG	Sunitinib (Sutent)	Sunitinib 50 mg once daily 4 weeks on, 2 weeks off, and after discontinuation (due to PD or toxicity), followed by sorafenib 400 mg BID
DRUG	Sorafenib (Nexavar)	Sorafenib 400 mg BID, followed by Sunitinib 50 mg once daily 4 weeks on, 2 weeks off, and after discontinuation (due to PD or toxicity)

Timeline

• Start date: 2009-01-01
• Primary completion: 2013-10-01
• Completion: 2013-12-01
• First posted: 2008-08-12
• Last updated: 2014-04-23

Locations

1 site across 1 country: Germany