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Renal Cell CarcinomaPhase 3NCT01613846

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)

A Phase 3 study testing Sorafenib+Pazopanib and Pazopanib+Sorafenib in people with Renal Cell Carcinoma, run by Technical University of Munich at 72 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 85 years
Conditions the study is for
Renal Cell Carcinoma
What is being tested?
Sorafenib+Pazopanib and Pazopanib+Sorafenib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
544 participants
Where
72 sitesin 3 countries
Study dates
May 2012to 30 Oct 2016
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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%)
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  • 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
  • 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).
  • Serum creatinine < 2x upper limit of normal
  • Written Informed Consent

Who cannot join

  • 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)
  • Uncontrolled hypertension (defined as blood pressure ≥ 150 mmHg systolic and/or ≥ 90 mmHg diastolic on medication).
  • History of HIV infection or chronic hepatitis B or C
  • 4. Active clinically serious infections (> grade 2 NCI-CTC version 4.03)
  • 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)
  • Patients with seizure disorder requiring medication (such as steroids or anti-epileptics)
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  • Patients with evidence or history of bleeding diathesis
  • History of organ allograft
  • Major surgery within 4 weeks of start of study
  • Autologous bone marrow transplant or stem cell rescue within 4 months before study start.
  • 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
  • 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)
  • Corrected QT Interval (QTc) > 480 msecs
  • Untreated hypothyroidism
  • Patients undergoing renal dialysis
  • 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
  • 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
  • Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
  • Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study
  • Patients unable to swallow oral medications
  • Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product
  • Known allergy to Votrient or Nexavar (i.e. to active substance or one of the constituents)
  • Prior exposure to study drugs.
  • Investigational drug therapy within 4 weeks of study entry.
  • Use of biologic response modifiers, such as G-CSF and other hematopoietic growth factors, within 3 weeks of study entry
  • Radiotherapy within 3 weeks of start of study drug and planned radiotherapy during the study
  • Concomitant medication: Any condition at the discretion of the investigator that precludes compliance with concomitant therapy restrictions described below.

Trial locations and contacts

72 sites in 3 countries.

72 sites in 3 countries

Germany62 sites

  • Universitätsklinikum Aachen, Urologische Klinik

    Aachen, 51074

  • Gesundheitszentrum St. Marien GmbH

    Amberg, 92224

  • Praxis für Urologie

    Berlin, 13055

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

    Berlin, 13353

  • Gemeinschaftspraxis Pott / Tirier / Hannig - Onkologie

    Bottrop, 46236

  • Urologie im Schlosscarrée Braunschweig

    Braunschweig, 38100

  • Klinikum Bremen-Mitte gGmbH

    Bremen, 28177

  • Bethanien Krankenhaus Chemnitz gGmbH

    Chemnitz, 09130

  • Überörtliche Gemeinschaftspraxis

    Cologne, 50968

  • Onkologische Gemeinschaftspraxis Dörfel/Göhler

    Dresden, 01127

  • Universitätsklinikum Carl Gustav Carus der Technischen Universität Dresden

    Dresden, 01307

  • Urologische Gemeinschaftspraxis

    Duisburg, 47179

  • Krankenhaus Düren gGmbH

    Düren, 52351

  • Universitätsklinikum Düsseldorf

    Düsseldorf, 40225

  • Urologische Facharztpraxis

    Eisleben Lutherstadt, 06295

  • Urologie Neandertal - Ortsübergreifende Gemeinschaftspraxis für Urologie

    Erkrath, 40699

  • Waldkrankenhaus St. Marien

    Erlangen, 91054

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

    Eschweiler, 52249

  • Hämato-onkologische Gemeinschaftspraxis

    Essen, 45136

  • Onkozentrum Freiberg

    Freiberg, 09599

  • Praxis für interdisziplinäre Onkologie & Hämatologie

    Freiburg im Breisgau, 79106

  • Universitätsklinikum Freiburg

    Freiburg im Breisgau, 79106

  • MVZ Osthessen GmbH

    Fulda, 36043

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

    Fürth, 90766

  • Onkologische Schwerpunktpraxis

    Goslar, 38642

  • Universitätsklinikum Göttingen

    Göttingen, 37075

  • Universitätsmedizin Greifswald

    Greifswald, 17475

  • St. Antonius-Hospital Gronau GmbH

    Gronau, 48599

  • Onkologische Schwerpunktpraxis

    Hamburg, 20095

  • Asklepios Klinik Altona

    Hamburg, 22763

  • Universitätsklinikum Heidelberg, Klinik für Urologie

    Heidelberg, 69120

  • Urologie-Heinsberg

    Heinsberg, 52525

  • Onkologische Praxis

    Hildesheim, 331135

  • Universitätsklinikum des Saarlandes

    Homburg, 66421

  • Universitätsklinikum Jena, Klinik für Urologie

    Jena, 07743

  • Praxis für Urologie

    Lauenburg, 21481

  • Onkologische Schwerpunktpraxis Leer - Emden

    Leer, 26789

  • MVZ Mitte/ MVZ Delitzsch GmbH

    Leipzig, 04103

  • Universitätsklinikum Magdeburg A.ö.R

    Magdeburg, 39120

  • Universitätsklinik Mannheim

    Mannheim, 68167

  • Philips-Universität-Marburg, Urologie und Kinderurologie

    Marburg, 35043

  • Praxis Markkleeberg

    Markkleeberg, 04416

  • Kliniken Maria Hilf

    Mönchengladbach, 41063

  • PUR/R Praxisklinik Urologie Rhein Rhur

    Mühlheim, 45458

  • Klinikum r. d. Isar, Klinik für Urologie

    München, 81675

  • Universitätsklinikum Münster , Klinik für Urologie

    Münster, 48149

  • Eps- early phase solutions GmbH

    Pößneck

  • Caritas Krankenhaus St. Josef

    Regensburg, 93053

  • Universitätsklinikum Rostock

    Rostock, 18055

  • Zentrum für Urologie und Onkologie

    Rostock, 18107

  • Diakoniekrankenhaus Rotenburg (Wümme) gGmbH

    Rotenburg (Wümme), 27356

  • Klinikum Sindelfingen-Böblingen

    Sindelfingen, 71065

  • Marienhospital / Innere Med III Onko Hämato Palliativm

    Stuttgart, 70199

  • Eberhard-Karls-Universität Tübingen

    Tübingen, 72076

  • Universitätsklinik Ulm

    Ulm, 89075

  • Universitätsklinikum Ulm

    Ulm, 89081

  • Praxis für Hämatologie und internistische Onkologie

    Velbert, 42551

  • Klinikum Nordoberpfalz AG

    Weiden, 92637

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

    Wiesbaden, 65191

  • Praxisgemeinschaft für Onkologie und Urologie

    Wilhelmshaven, 26389

  • Gemeinschaftspraxis für Urologie

    Wuppertal, 42103

  • Universitätsklinikum Würzburg

    Würzburg, 97080

Other trials in Germany

Netherlands6 sites

  • Onze Lieve Vrouwe Gasthuis

    Amsterdam, 1091 HA

  • Reinier de Graaf Gasthuis

    Delft, 2600 AG

  • Spaarne Ziekenhuis

    Hoofddorp, 2130 AT

  • HAGA

    The Hague, 2545

  • TweeSteden Ziekenhuis

    Tilburg, 5042 AD

  • VieCuri Medical Center

    Venlo, 5912 BL

Other trials in Netherlands

Austria4 sites

  • Medizinische Universität Innsbruck

    Innsbruck, 6020

  • A. ö. Bezirkskrankenhaus Kufstein

    Kufstein, 6330

  • AKH Linz GmbH

    Linz, 4020

  • LKH Salzburg

    Salzburg, 5020

Other trials in Austria

About this study

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

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.

Being tested
Sorafenib+Pazopanib, Pazopanib+Sorafenib
Medical subject headings
Carcinoma, Renal Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Sorafenib+PazopanibDrug

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

  • Pazopanib+SorafenibDrug

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

Study groups in NCT01613846
Study groupRoleWhat they receive
Sorafenib followed by pazopanibExperimentalSorafenib 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).
Receives: Drug: Sorafenib+Pazopanib
Pazopanib followed by SorafenibExperimentalPazopanib 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).
Receives: Drug: Pazopanib+Sorafenib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 4 years

Secondary outcomes (8)

  1. Time from randomization to progression during second-line therapy (total TTP)

    Measured: 1 year

  2. Time to first-line treatment failure (progression, death, discontinuation due to toxicity) descriptively in each arm

    Measured: 1 year

  3. PFS in first-line and second-line treatment, descriptively

    Measured: 4 years

  4. Overall survival, descriptively (data cut-off same as for primary endpoint

    Measured: 4 years

  5. Disease Control Rate (DCR); Response rates in first-line and in second-line (CR, PR, SD according to RECIST criteria)

    Measured: 4 years

  6. Health-related Quality of Life (FACIT-F, FKSI-10)

    Measured: 4 years

  7. Biomarker programme

    Circulating tumor cells, Single Nucleotide Polymorphisms, Serum Protein Signatures

    Measured: 4 years

  8. Safety and tolerability

    Monitoring of adverse events, summaries and listings of adverse events

    Measured: 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Jun 2012 (estimated)
  2. Study startMay 2012
  3. Primary completion30 Oct 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
544 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01613846
Sponsor's protocol ID
16037 / AN 33/11
Other IDs
2011-004396-36
Status last verified
Apr 2017
First submitted
4 May 2012
Last updated
20 Apr 2017
Results posted
No

Publications

  • 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.

    PubMed 37146227

  • 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.

    PubMed 30529901

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Sorafenib+Pazopanib and Pazopanib+Sorafenib in people with Renal Cell Carcinoma, run by Technical University of Munich at 72 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 29 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 72 sites in Germany, Netherlands, Austria. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01613846, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Apr 2017.

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