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
- Conditions
- advanced / metastatic renal cell carcinomaadvanced/ disseminated renal cell kidney cancer10038364
- Registration Number
- NL-OMON43677
- Lead Sponsor
- Dekan der Fakultät für Medizin der Technischen Universität München
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 45
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 Performance Status (ECOG,
Karnofsky)*)
4. MSKCC prognostic score (2004), low or intermediate (see appendix *15.2
Motzer Scoring*)
5. Life expectancy of at least 12 weeks
6. Subjects with at least one uni-dimensional (for RECIST 1.1, see appendix *15.3
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/*l
* Platelet count * 100,000/*l
* 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
* 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 < 2 x upper limit of normal
8. Written Informed Consent
_____________________________________________________________________
*Based on references:
o Kirchner H., H. Heinzer, J. Roigas und F. Overkamp: Differentialtherapie beim
metastasierenden Nierenzellkarzinom. Der Onkologe 2008; 14: 191-197;
o SmPC of interleukin-2
o SmPC of interferon alfa -2a
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 antiepileptics)
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
grow
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Total Progression Free Survival</p><br>
- Secondary Outcome Measures
Name Time Method <p>1. Time from randomization to progression during second-line therapy (total TTP)<br /><br>2. Time to first-line treatment failure (progression, death, discontinuation<br /><br>due to toxicity) descriptively in each arm<br /><br>3. PFS in first-line and second-line treatment, descriptively<br /><br>4. Overall survival, descriptively (data cut-off same as for primary endpoint)<br /><br>5. Disease Control Rate (DCR); Response rates in first-line and in second-line<br /><br>(CR, PR, SD according to RECIST criteria)<br /><br>6. Health-related Quality of Life (FACIT-F, FKSI-10)<br /><br>7. Veiligheid en verdraagbaarheid</p><br>