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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

Phase 3
18 Years
85 Years
Open (Enrolling)
Renal Cell Carcinoma

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Trial Information

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

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

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

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

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

Type of Study:


Study Design:

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

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.

Outcome Time Frame:

4 years

Safety Issue:


Principal Investigator

Jürgen E. Gschwend, Prof.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Klinikum rechts der Isar, TU München


Germany: Federal Institute for Drugs and Medical Devices

Study ID:

16037 / AN 33/11



Start Date:

May 2012

Completion Date:

Related Keywords:

  • Renal Cell Carcinoma
  • Carcinoma
  • Carcinoma, Renal Cell