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)
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
2 other identifiers
interventional
544
3 countries
72
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
72 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
May 1, 2012
CompletedFirst Submitted
Initial submission to the registry
May 4, 2012
CompletedFirst Posted
Study publicly available on registry
June 7, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 30, 2016
CompletedApril 20, 2017
April 1, 2017
4.5 years
May 4, 2012
April 19, 2017
Conditions
Outcome Measures
Primary Outcomes (1)
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 Outcomes (8)
Time from randomization to progression during second-line therapy (total TTP)
1 year
Time to first-line treatment failure (progression, death, discontinuation due to toxicity) descriptively in each arm
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
Disease Control Rate (DCR); Response rates in first-line and in second-line (CR, PR, SD according to RECIST criteria)
4 years
- +3 more secondary outcomes
Study Arms (2)
Sorafenib followed by pazopanib
EXPERIMENTALSorafenib 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).
Pazopanib followed by Sorafenib
EXPERIMENTALPazopanib 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).
Interventions
Sorafenib (first-line) followed by Pazopanib (second-line)
Pazopanib (first-line) followed by Sorafenib (second-line)
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- Non-symptomatic brain metastases
- Severe lung disease (e.g. PAH, COPD) with Pa O2 \< 60 mmHg on rest
- Age ≥ 18 and ≤ 85 years
- Karnofsky Index ≥ 70% (see appendix 15.1)
- MSKCC prognostic score (2004), low or intermediate (see appendix 15.2)
- Life expectancy of at least 12 weeks
- Subjects with at least one uni-dimensional (for RECIST 1.1) measurable lesion. Lesions must be measured by CT/MRI- scan
- 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).
- +29 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (72)
Medizinische Universität Innsbruck
Innsbruck, 6020, Austria
A. ö. Bezirkskrankenhaus Kufstein
Kufstein, 6330, Austria
AKH Linz GmbH
Linz, 4020, Austria
LKH Salzburg
Salzburg, 5020, Austria
Universitätsklinikum Aachen, Urologische Klinik
Aachen, 51074, Germany
Gesundheitszentrum St. Marien GmbH
Amberg, 92224, Germany
Praxis für Urologie
Berlin, 13055, Germany
Charite Campus Virchow Klinikum / Klein. Für Innere Med / Onkologie/Hämatologie
Berlin, 13353, Germany
Gemeinschaftspraxis Pott / Tirier / Hannig - Onkologie
Bottrop, 46236, Germany
Urologie im Schlosscarrée Braunschweig
Braunschweig, 38100, Germany
Klinikum Bremen-Mitte gGmbH
Bremen, 28177, Germany
Bethanien Krankenhaus Chemnitz gGmbH
Chemnitz, 09130, Germany
Überörtliche Gemeinschaftspraxis
Cologne, 50968, Germany
Onkologische Gemeinschaftspraxis Dörfel/Göhler
Dresden, 01127, Germany
Universitätsklinikum Carl Gustav Carus der Technischen Universität Dresden
Dresden, 01307, Germany
Urologische Gemeinschaftspraxis
Duisburg, 47179, Germany
Krankenhaus Düren gGmbH
Düren, 52351, Germany
Universitätsklinikum Düsseldorf
Düsseldorf, 40225, Germany
Urologische Facharztpraxis
Eisleben Lutherstadt, 06295, Germany
Urologie Neandertal - Ortsübergreifende Gemeinschaftspraxis für Urologie
Erkrath, 40699, Germany
Waldkrankenhaus St. Marien
Erlangen, 91054, Germany
St.-Antonius-Hospital in Eschweiler / Klinik f. Hämatologie und Onkologie
Eschweiler, 52249, Germany
Hämato-onkologische Gemeinschaftspraxis
Essen, 45136, Germany
Onkozentrum Freiberg
Freiberg, 09599, Germany
Praxis für interdisziplinäre Onkologie & Hämatologie
Freiburg im Breisgau, 79106, Germany
Universitätsklinikum Freiburg
Freiburg im Breisgau, 79106, Germany
MVZ Osthessen GmbH
Fulda, 36043, Germany
Gem.praxis Dres. J. Wilke, H. Wagner - Hämatol.u.intern.Onkol. am Klinikum Fürth
Fürth, 90766, Germany
Onkologische Schwerpunktpraxis
Goslar, 38642, Germany
Universitätsklinikum Göttingen
Göttingen, 37075, Germany
Universitätsmedizin Greifswald
Greifswald, 17475, Germany
St. Antonius-Hospital Gronau GmbH
Gronau, 48599, Germany
Onkologische Schwerpunktpraxis
Hamburg, 20095, Germany
Asklepios Klinik Altona
Hamburg, 22763, Germany
Universitätsklinikum Heidelberg, Klinik für Urologie
Heidelberg, 69120, Germany
Urologie-Heinsberg
Heinsberg, 52525, Germany
Onkologische Praxis
Hildesheim, 331135, Germany
Universitätsklinikum des Saarlandes
Homburg, 66421, Germany
Universitätsklinikum Jena, Klinik für Urologie
Jena, 07743, Germany
Praxis für Urologie
Lauenburg, 21481, Germany
Onkologische Schwerpunktpraxis Leer - Emden
Leer, 26789, Germany
MVZ Mitte/ MVZ Delitzsch GmbH
Leipzig, 04103, Germany
Universitätsklinikum Magdeburg A.ö.R
Magdeburg, 39120, Germany
Universitätsklinik Mannheim
Mannheim, 68167, Germany
Philips-Universität-Marburg, Urologie und Kinderurologie
Marburg, 35043, Germany
Praxis Markkleeberg
Markkleeberg, 04416, Germany
Kliniken Maria Hilf
Mönchengladbach, 41063, Germany
PUR/R Praxisklinik Urologie Rhein Rhur
Mühlheim, 45458, Germany
Klinikum r. d. Isar, Klinik für Urologie
München, 81675, Germany
Universitätsklinikum Münster , Klinik für Urologie
Münster, 48149, Germany
Eps- early phase solutions GmbH
Pößneck, Germany
Caritas Krankenhaus St. Josef
Regensburg, 93053, Germany
Universitätsklinikum Rostock
Rostock, 18055, Germany
Zentrum für Urologie und Onkologie
Rostock, 18107, Germany
Diakoniekrankenhaus Rotenburg (Wümme) gGmbH
Rotenburg (Wümme), 27356, Germany
Klinikum Sindelfingen-Böblingen
Sindelfingen, 71065, Germany
Marienhospital / Innere Med III Onko Hämato Palliativm
Stuttgart, 70199, Germany
Eberhard-Karls-Universität Tübingen
Tübingen, 72076, Germany
Universitätsklinik Ulm
Ulm, 89075, Germany
Universitätsklinikum Ulm
Ulm, 89081, Germany
Praxis für Hämatologie und internistische Onkologie
Velbert, 42551, Germany
Klinikum Nordoberpfalz AG
Weiden, 92637, Germany
Gesellsch. z. Förd. Von Wissenschaft u.Qualitätssicherung i.d.ambul.Onkologie
Wiesbaden, 65191, Germany
Praxisgemeinschaft für Onkologie und Urologie
Wilhelmshaven, 26389, Germany
Gemeinschaftspraxis für Urologie
Wuppertal, 42103, Germany
Universitätsklinikum Würzburg
Würzburg, 97080, Germany
Onze Lieve Vrouwe Gasthuis
Amsterdam, 1091 HA, Netherlands
Reinier de Graaf Gasthuis
Delft, 2600 AG, Netherlands
Spaarne Ziekenhuis
Hoofddorp, 2130 AT, Netherlands
HAGA
The Hague, 2545, Netherlands
TweeSteden Ziekenhuis
Tilburg, 5042 AD, Netherlands
VieCuri Medical Center
Venlo, 5912 BL, Netherlands
Related Publications (2)
Aldin A, Besiroglu B, Adams A, Monsef I, Piechotta V, Tomlinson E, Hornbach C, Dressen N, Goldkuhle M, Maisch P, Dahm P, Heidenreich A, Skoetz N. First-line therapy for adults with advanced renal cell carcinoma: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2023 May 4;5(5):CD013798. doi: 10.1002/14651858.CD013798.pub2.
PMID: 37146227DERIVEDRetz M, Bedke J, Bogemann M, Grimm MO, Zimmermann U, Muller L, Leiber C, Teber D, Wirth M, Bolenz C, van Alphen R, De Santis M, Beeker A, Lehmann J, Indorf M, Frank M, Bokemeyer C, Gschwend JE. SWITCH II: Phase III randomized, sequential, open-label study to evaluate the efficacy and safety of sorafenib-pazopanib versus pazopanib-sorafenib in the treatment of advanced or metastatic renal cell carcinoma (AUO AN 33/11). Eur J Cancer. 2019 Jan;107:37-45. doi: 10.1016/j.ejca.2018.11.001. Epub 2018 Dec 7.
PMID: 30529901DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Jürgen E. Gschwend, Prof.
Klinikum rechts der Isar, TU München
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 4, 2012
First Posted
June 7, 2012
Study Start
May 1, 2012
Primary Completion
October 30, 2016
Last Updated
April 20, 2017
Record last verified: 2017-04