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)

NCT ID: NCT01613846

Last Updated: 2017-04-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 544 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-05-31

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.

Conditions

Renal Cell Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: EXPERIMENTAL

Sorafenib+Pazopanib

Intervention Type: DRUG

Sorafenib (first-line) followed by Pazopanib (second-line)

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).

Group Type: EXPERIMENTAL

Pazopanib+Sorafenib

Intervention Type: DRUG

Pazopanib (first-line) followed by Sorafenib (second-line)

Interventions

Sorafenib+Pazopanib

Sorafenib (first-line) followed by Pazopanib (second-line)

Intervention Type: DRUG

Pazopanib+Sorafenib

Pazopanib (first-line) followed by Sorafenib (second-line)

Intervention Type: DRUG

Eligibility Criteria

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

Exclusion Criteria

• 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

1. History of cardiac disease: congestive heart failure > NYHA class 2 or with LVEF at baseline echocardiography < 50%, (echocardiography is optional); active CAD (MI more than 6 months prior to study entry is allowed); cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted)

2. Uncontrolled hypertension (defined as blood pressure ≥ 150 mmHg systolic and/or ≥ 90 mmHg diastolic on medication).

3. History of HIV infection or chronic hepatitis B or C

4. 4. Active clinically serious infections (> grade 2 NCI-CTC version 4.03)

5. Symptomatic metastatic brain or meningeal tumors (unless the patient is > 6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry)

6. Patients with seizure disorder requiring medication (such as steroids or anti-epileptics)

7. Patients with evidence or history of bleeding diathesis

8. History of organ allograft

9. Major surgery within 4 weeks of start of study

10. Autologous bone marrow transplant or stem cell rescue within 4 months before study start.

11. Any significant condition that increases the risk for bleeding, including, but not limited to active peptic ulcer disease, inflammatory bowel disease, known intraluminal or endobronchial metastatic lesions and/or lesions infiltrating major pulmonary vessels with risk of bleeding, presence of non-healing wound or trauma within 4 weeks prior to first dose of investigational drug

12. History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep vein thrombosis (DVT) within the past 6 months (Note: Subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible)

13. Corrected QT Interval (QTc) > 480 msecs

14. Untreated hypothyroidism

15. Patients undergoing renal dialysis

16. Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors [Ta, Tis & T1] or any cancer curatively treated > 3 years prior to study entry

17. Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Both men and women enrolled in this trial must use adequate barrier birth control measures (with a Pearl Index < 1) during the course of the trial and 3 months after the completion of trial

18. Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results

19. Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study

20. Patients unable to swallow oral medications

21. Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product

22. Known allergy to Votrient or Nexavar (i.e. to active substance or one of the constituents)

23. Prior exposure to study drugs.

24. Investigational drug therapy within 4 weeks of study entry.

25. Use of biologic response modifiers, such as G-CSF and other hematopoietic growth factors, within 3 weeks of study entry

26. Radiotherapy within 3 weeks of start of study drug and planned radiotherapy during the study

27. Concomitant medication: Any condition at the discretion of the investigator that precludes compliance with concomitant therapy restrictions described below.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Technical University of Munich

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jürgen E. Gschwend, Prof.

Role: PRINCIPAL_INVESTIGATOR

Klinikum rechts der Isar, TU München

Locations

Medizinische Universität Innsbruck

Innsbruck, , Austria

A. ö. Bezirkskrankenhaus Kufstein

Kufstein, , Austria

AKH Linz GmbH

Linz, , Austria

LKH Salzburg

Salzburg, , Austria

Universitätsklinikum Aachen, Urologische Klinik

Aachen, , Germany

Gesundheitszentrum St. Marien GmbH

Amberg, , Germany

Praxis für Urologie

Berlin, , Germany

Charite Campus Virchow Klinikum / Klein. Für Innere Med / Onkologie/Hämatologie

Berlin, , Germany

Gemeinschaftspraxis Pott / Tirier / Hannig - Onkologie

Bottrop, , Germany

Urologie im Schlosscarrée Braunschweig

Braunschweig, , Germany

Klinikum Bremen-Mitte gGmbH

Bremen, , Germany

Bethanien Krankenhaus Chemnitz gGmbH

Chemnitz, , Germany

Überörtliche Gemeinschaftspraxis

Cologne, , Germany

Onkologische Gemeinschaftspraxis Dörfel/Göhler

Dresden, , Germany

Universitätsklinikum Carl Gustav Carus der Technischen Universität Dresden

Dresden, , Germany

Urologische Gemeinschaftspraxis

Duisburg, , Germany

Krankenhaus Düren gGmbH

Düren, , Germany

Universitätsklinikum Düsseldorf

Düsseldorf, , Germany

Urologische Facharztpraxis

Eisleben Lutherstadt, , Germany

Urologie Neandertal - Ortsübergreifende Gemeinschaftspraxis für Urologie

Erkrath, , Germany

Waldkrankenhaus St. Marien

Erlangen, , Germany

St.-Antonius-Hospital in Eschweiler / Klinik f. Hämatologie und Onkologie

Eschweiler, , Germany

Hämato-onkologische Gemeinschaftspraxis

Essen, , Germany

Onkozentrum Freiberg

Freiberg, , Germany

Praxis für interdisziplinäre Onkologie & Hämatologie

Freiburg im Breisgau, , Germany

Universitätsklinikum Freiburg

Freiburg im Breisgau, , Germany

MVZ Osthessen GmbH

Fulda, , Germany

Gem.praxis Dres. J. Wilke, H. Wagner - Hämatol.u.intern.Onkol. am Klinikum Fürth

Fürth, , Germany

Onkologische Schwerpunktpraxis

Goslar, , Germany

Universitätsklinikum Göttingen

Göttingen, , Germany

Universitätsmedizin Greifswald

Greifswald, , Germany

St. Antonius-Hospital Gronau GmbH

Gronau, , Germany

Onkologische Schwerpunktpraxis

Hamburg, , Germany

Asklepios Klinik Altona

Hamburg, , Germany

Universitätsklinikum Heidelberg, Klinik für Urologie

Heidelberg, , Germany

Urologie-Heinsberg

Heinsberg, , Germany

Onkologische Praxis

Hildesheim, , Germany

Universitätsklinikum des Saarlandes

Homburg, , Germany

Universitätsklinikum Jena, Klinik für Urologie

Jena, , Germany

Praxis für Urologie

Lauenburg, , Germany

Onkologische Schwerpunktpraxis Leer - Emden

Leer, , Germany

MVZ Mitte/ MVZ Delitzsch GmbH

Leipzig, , Germany

Universitätsklinikum Magdeburg A.ö.R

Magdeburg, , Germany

Universitätsklinik Mannheim

Mannheim, , Germany

Philips-Universität-Marburg, Urologie und Kinderurologie

Marburg, , Germany

Praxis Markkleeberg

Markkleeberg, , Germany

Kliniken Maria Hilf

Mönchengladbach, , Germany

PUR/R Praxisklinik Urologie Rhein Rhur

Mühlheim, , Germany

Klinikum r. d. Isar, Klinik für Urologie

München, , Germany

Universitätsklinikum Münster , Klinik für Urologie

Münster, , Germany

Eps- early phase solutions GmbH

Pößneck, , Germany

Caritas Krankenhaus St. Josef

Regensburg, , Germany

Universitätsklinikum Rostock

Rostock, , Germany

Zentrum für Urologie und Onkologie

Rostock, , Germany

Diakoniekrankenhaus Rotenburg (Wümme) gGmbH

Rotenburg (Wümme), , Germany

Klinikum Sindelfingen-Böblingen

Sindelfingen, , Germany

Marienhospital / Innere Med III Onko Hämato Palliativm

Stuttgart, , Germany

Eberhard-Karls-Universität Tübingen

Tübingen, , Germany

Universitätsklinik Ulm

Ulm, , Germany

Universitätsklinikum Ulm

Ulm, , Germany

Praxis für Hämatologie und internistische Onkologie

Velbert, , Germany

Klinikum Nordoberpfalz AG

Weiden, , Germany

Gesellsch. z. Förd. Von Wissenschaft u.Qualitätssicherung i.d.ambul.Onkologie

Wiesbaden, , Germany

Praxisgemeinschaft für Onkologie und Urologie

Wilhelmshaven, , Germany

Gemeinschaftspraxis für Urologie

Wuppertal, , Germany

Universitätsklinikum Würzburg

Würzburg, , Germany

Onze Lieve Vrouwe Gasthuis

Amsterdam, , Netherlands

Reinier de Graaf Gasthuis

Delft, , Netherlands

Spaarne Ziekenhuis

Hoofddorp, , Netherlands

HAGA

The Hague, , Netherlands

TweeSteden Ziekenhuis

Tilburg, , Netherlands

VieCuri Medical Center

Venlo, , Netherlands

Countries

Austria; Germany; Netherlands

References

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.

Reference Type: DERIVED

PMID: 37146227 (View on PubMed)

Retz 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.

Reference Type: DERIVED

PMID: 30529901 (View on PubMed)

Other Identifiers

2011-004396-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

16037 / AN 33/11

Identifier Type: -

Identifier Source: org_study_id

NCT02083094

Identifier Type: -

Identifier Source: nct_alias