Overview
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)
Status:
Completed
Completed
Trial end date:
1969-12-31
1969-12-31
Target enrollment:
0
0
Participant gender:
All
All
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.Phase:
Phase 3Accepts Healthy Volunteers?
NoDetails
Lead Sponsor:
Technische Universität MünchenTreatments:
Niacinamide
Sorafenib
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
- 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.