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)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2013 by Technische Universität München
Sponsor:
Information provided by (Responsible Party):
Technische Universität München
ClinicalTrials.gov Identifier:
NCT01613846
First received: May 4, 2012
Last updated: April 25, 2013
Last verified: April 2013
  Purpose

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.


Condition Intervention Phase
Renal Cell Carcinoma
Drug: Sorafenib+Pazopanib
Drug: Pazopanib+Sorafenib
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Technische Universität München:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time from randomization to progression during second-line therapy (total TTP) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Time to first-line treatment failure (progression, death, discontinuation due to toxicity) descriptively in each arm [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • PFS in first-line and second-line treatment, descriptively [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • Overall survival, descriptively (data cut-off same as for primary endpoint [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • Disease Control Rate (DCR); Response rates in first-line and in second-line (CR, PR, SD according to RECIST criteria) [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • Health-related Quality of Life (FACIT-F, FKSI-10) [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • Biomarker programme [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    Circulating tumor cells, Single Nucleotide Polymorphisms, Serum Protein Signatures

  • Safety and tolerability [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
    Monitoring of adverse events, summaries and listings of adverse events


Estimated Enrollment: 544
Study Start Date: May 2012
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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).

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

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

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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. Cytokine unsuitability will be determined by means of a checklist (see appendix 15.1)
  2. Age ≥ 18 and ≤ 85 years
  3. Karnofsky Index ≥ 70% (see appendix 15.2)
  4. MSKCC prognostic score (2004), low or intermediate (see appendix 15.3)
  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 neurophil count (ANC)>1,500/µl
    • Platelet count >=100,000/µl
    • Total bilirubin < 1.5x the upper limit of normal (Note: Subjects with Gilbert´s Syndrome are eligible if their total bilirubin is <3.0 X ULN and direct bilirubin is ≤35%)
    • ALAT and ASAT < 2.5x upper limit of normal (Note: concomitant elevations in bilirubin and ASAT/ALAT above 1.0x upper limit of normal are not permitted).
    • Alkaline phosphatase < 4x upper limit of normal
    • PI-INR/PT < 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 or anticoagulation and no prior evidence of underlying abnormality in these parameters exists.]
    • Serum creatinie < 2 x 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. 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. 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, major surgery or trauma within 4 weeks prior to first dose of investigational drug
  10. 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 anticoagulating agents for at least 6 weeks are eligible)
  11. Corrected QT Interval (QTc) > 480 msecs
  12. Untreated hypothyroidism
  13. Patients undergoing renal dialysis
  14. 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
  15. 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 trail
  16. Substance abuse, medical, psychological or social conditions that may interfere with the patient´s participation in the study or evaluation of the study results
  17. Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study
  18. Patients unable to swallow oral medications
  19. Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product
  20. Known allergy to Votrient® or Nexavar® (i.e to active substance or one of the constituents)
  21. Anticancer chemo-, cytokine- or targeted therapy for RCC
  22. Radiotherapy during study or within 3 weeks or start of study drug (Palliative radiotherapy will be allowed).
  23. Major surgery within 4 weeks of start of study (if wound healing is considered to be completed investigator can decide to start with study earlier).
  24. Autologous bone marrow transplant or stem cell rescue within 4 months of study
  25. Use of biologic response modifiers, such as G-CSF, within 3 weeks of study entry. [G-CSF and other hematopoietic growth factors may be used in the management of acute toxicity such as febrile neutropenia when clinically indicated or at the discretion of the investigator, however they may not be substituted for a required dose reduction.] [Patients taking chronic erythropoietin are permitted provided no dose adjustment is undertaken within 2 months prior to the study or during the study]
  26. Investigational drug therapy outside of this trial during or within 4 weeks of study entry
  27. Prior exposure to the study drugs
  28. Any St. John´s wort containing remedy
  29. Strong CYP3A4 inhibitors during pazopanib therapy
  30. Grapefruit juice during pazopnib therapy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01613846

Contacts
Contact: Stefan Jänich, Dr. +49(0) 761 / 152 42-19 stefan.jaenich@iomedico.com
Contact: Martina Rudmann 49(0) 791/ 152 42-61 martina.rudmann@iomedico.com

  Show 69 Study Locations
Sponsors and Collaborators
Technische Universität München
Investigators
Principal Investigator: Jürgen E. Gschwend, Prof. Klinikum rechts der Isar, TU München
  More Information

No publications provided

Responsible Party: Technische Universität München
ClinicalTrials.gov Identifier: NCT01613846     History of Changes
Other Study ID Numbers: 16037 / AN 33/11, 2011-004396-36
Study First Received: May 4, 2012
Last Updated: April 25, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Sorafenib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 24, 2014