E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
First-line advanced / metastatic renal cell carcinoma |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10050513 |
E.1.2 | Term | Metastatic renal cell carcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary: To evaluate if progression-free survival from first treatment to progression or death during second-line therapy (total PFS) of sorafenib followed by sunitinib is superior compared to sunitinib followed by sorafenib. |
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E.2.2 | Secondary objectives of the trial |
Secondary: 1. Time from first treatment to confirmed progression during second-line therapy (total TTP) 2. Time to first line treatment failure (progression, discontinuation due to toxicity) descriptively in each arm 3. PFS in first-line and second-line treatment, descriptively 4. Overall survival, descriptively (Data cut-off same as used for primary endpoint) 5. Disease Control Rate (DCR); Response rates in first-line and in second line (CR,PR, SD, according to RECIST criteria) 6. Cardiotoxicity analysis by means of echocardiography and NT-pro BNP with aninterim analysis after 100 patients of each arm have completed the study 7. Safety and tolerability |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 therapy 2. Age >= 18 years and <= 85 years 3. ECOG Performance Status of 0 or 1 4. MSKCC (1999) prognostic score, low or intermediate 5. Life expectancy of at least 12 weeks. 6. Subjects with at least one uni-dimensional (for RECIST) 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/mm3 - Platelet count 100,000/μl - Total bilirubin < 1.5 times the upper limit of normal - ALT and AST < 2.5 x upper limit of normal (< 5 x upper limit of normal for patients with liver involvement of their cancer) - Alkaline phosphatase < 4 x upper limit of normal - PT-INR/PT < 1.5 x 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 no prior evidence of underlying abnormality in these parameters exists.] - Serum creatinine </= 2 x upper limit of normal.
8. Written Informed Consent
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E.4 | Principal exclusion criteria |
1. History of cardiac disease: congestive heart failure >NYHA class 2 or with LVEF at baseline echocardiography <50%; 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) or uncontrolled hypertension (defined as blood pressure >= 160 mmHg systolic and/or >= 90 mmHg diastolic on medication). 2. History of HIV infection or chronic hepatitis B or C 3. Active clinically serious infections (> grade 2 NCI-CTC version 3.0) 4. 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) 5. Patients with seizure disorder requiring medication (such as steroids or anti-epileptics) 6. History of organ allograft 7. Patients with evidence or history of bleeding diathesis 8. Untreated hypothyrosis 9. Patients undergoing renal dialysis 10. 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. 11. 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 during the course of the trial and 3 months after the completion of trial. 12. Substance abuse, medical, psychological or social conditions that may interfere with the patient’s participation in the study or evaluation of the study results 13. Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study 14. Patients unable to swallow oral medications 15. Known allergy to sunitinib or sorafenib or one of its constitutents
Excluded therapies and medications, previous and concomitant: 1. Anticancer chemotherapy or immunotherapy before study entry or during the study. 2. Radiotherapy during study or within 3 weeks of start of study drug. (Palliative radiotherapy will be allowed). Major surgery within 4 weeks of start of study 3. Autologous bone marrow transplant or stem cell rescue within 4 months of study 4. Use of biologic response modifiers, such as G-CSF, within 3 week 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] 5. Investigational drug therapy outside of this trial during or within 4 weeks of study entry 6. Prior exposure to the study drug. 7. Any St. John’s wort containing remedy |
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E.5 End points |
E.5.1 | Primary end point(s) |
To evaluate if progression-free survival from first treatment to progression or death during second-line therapy (total PFS) of sorafenib followed by sunitinib is superior compared to sunitinib followed by sorafenib. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After the study reached its primary endpoint cut off, i.e. after 194 endpoint events have occurred, clean data for these patients exist and a statistical analysis has been performed data collection will be stopped. After that the trial is terminated and a close out visit will be performed. Remaining patients will be treated outside the study and will be censored in the analysis. |
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E.5.2 | Secondary end point(s) |
Secondary: 1. Time from first treatment to confirmed progression during second-line therapy (total TTP) 2. Time to first line treatment failure (progression, discontinuation due to toxicity) descriptively in each arm 3. PFS in first-line and second-line treatment, descriptively 4. Overall survival, descriptively (Data cut-off same as used for primary endpoint) 5. Disease Control Rate (DCR); Response rates in first-line and in second line (CR,PR, SD, according to RECIST criteria) 6. Cardiotoxicity analysis by means of echocardiography and NT-pro BNP with aninterim analysis after 100 patients of each arm have completed the study 7. Safety and tolerability |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After the study reached its primary endpoint cut off, i.e. after 194 endpoint events have occurred, clean data for these patients exist and a statistical analysis has been performed data collection will be stopped. After that the trial is terminated and a close out visit will be performed. Remaining patients will be treated outside the study and will be censored in the analysis. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Sequential application of two study medications (Sorafenib-Sunitinib vs. Sunitinib-Sorafenib) |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 87 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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After the study reached its primary endpoint cut off, i.e. after 194 endpoint events have occurred, clean data for these patients exist and a statistical analysis has been performed data collection will be stopped. After that the trial is terminated and a close out visit will be performed. Remaining patients will be treated outside the study and will be censored in the analysis. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |