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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01613846
Other study ID # 16037 / AN 33/11
Secondary ID 2011-004396-36
Status Completed
Phase Phase 3
First received May 4, 2012
Last updated April 19, 2017
Start date May 2012

Study information

Verified date April 2017
Source Technische Universität München
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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. 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.


Other known NCT identifiers
  • NCT02083094

Recruitment information / eligibility

Status Completed
Enrollment 544
Est. completion date
Est. primary completion date October 30, 2016
Accepts healthy volunteers No
Gender All
Age group 18 Years to 85 Years
Eligibility 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

- 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

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

Exclusion Criteria:

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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Sorafenib+Pazopanib
Sorafenib (first-line) followed by Pazopanib (second-line)
Pazopanib+Sorafenib
Pazopanib (first-line) followed by Sorafenib (second-line)

Locations

Country Name City State
Austria Medizinische Universität Innsbruck Innsbruck
Austria A. ö. Bezirkskrankenhaus Kufstein Kufstein
Austria AKH Linz GmbH Linz
Austria LKH Salzburg Salzburg
Germany Universitätsklinikum Aachen, Urologische Klinik Aachen
Germany Gesundheitszentrum St. Marien GmbH Amberg
Germany Charite Campus Virchow Klinikum / Klein. Für Innere Med / Onkologie/Hämatologie Berlin
Germany Praxis für Urologie 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 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 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
Germany Universitätsklinikum Freiburg Freiburg
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 Asklepios Klinik Altona Hamburg
Germany Onkologische Schwerpunktpraxis 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 Überörtliche Gemeinschaftspraxis Köln
Germany Praxis für Urologie Lauenburg
Germany Onkologische Schwerpunktpraxis Leer - Emden Leer
Germany MVZ Mitte/ MVZ Delitzsch GmbH Leipzig
Germany Urologische Facharztpraxis Lutherstadt Eisleben
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
Netherlands Onze Lieve Vrouwe Gasthuis Amsterdam
Netherlands Reinier de Graaf Gasthuis Delft
Netherlands HAGA Den Haag
Netherlands Spaarne Ziekenhuis Hoofddorp
Netherlands TweeSteden Ziekenhuis Tilburg
Netherlands VieCuri Medical Center Venlo

Sponsors (1)

Lead Sponsor Collaborator
Technische Universität München

Countries where clinical trial is conducted

Austria,  Germany,  Netherlands, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 Time from randomization to progression during second-line therapy (total TTP) 1 year
Secondary Time to first-line treatment failure (progression, death, discontinuation due to toxicity) descriptively in each arm 1 year
Secondary PFS in first-line and second-line treatment, descriptively 4 years
Secondary Overall survival, descriptively (data cut-off same as for primary endpoint 4 years
Secondary Disease Control Rate (DCR); Response rates in first-line and in second-line (CR, PR, SD according to RECIST criteria) 4 years
Secondary Health-related Quality of Life (FACIT-F, FKSI-10) 4 years
Secondary Biomarker programme Circulating tumor cells, Single Nucleotide Polymorphisms, Serum Protein Signatures 4 years
Secondary Safety and tolerability Monitoring of adverse events, summaries and listings of adverse events 4 years
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