E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced renal cell cancer |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10050513 |
E.1.2 | Term | Metastatic renal cell carcinoma |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The aim of the study is to evaluate if the addition of low doses of IFN alpha-2a to sorafenib would be beneficial, by estimating the median PFS, in patients who have previously either progressed or are intolerant to sunitinib. The primary end-point is the PFS before dose escalation. |
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E.2.2 | Secondary objectives of the trial |
Secondary variables include response rate, time to progression, duration of response and overall survival. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Disease progression as defined by RECIST criteria following documented stable disease or better after at least 8 weeks of sunitinib as first-line treatment (or two cycles of 4 weeks on and 2 weeks off treatment) And/or patients who have discontinued sunitinib treatment at any point due to toxicity Study entry at least 2 weeks after treatment with sunitinib but up to a maximum of 8 weeks MSKCC prognostic score low or intermediate ECOG Performance Status of 0 or1 Patient must have histologically confirmed metastatic renal cell carcinoma with predominant clear cell histology (clear cell component more than 50%) Age > 18 years Life expectancy of at least 12 weeks Patients with at least one measurable lesion. Lesions must be measured by CT-scan or MRI (Magnetic Resonance Imaging) according to Response Evaluation Criteria in Solid Tumors (RECIST, see Appendix 10.5 ) Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening: 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 ULN PT or INR and PTT < 1.5 x upper limit of normal (patients who receive anti-coagulation treatment with an agent such as coumarin derivates or heparin will be allowed to participate. For patients on coumarin derivates , close monitoring of at least weekly evaluations will be performed until INR is stable based on a measurement at pre dose, as defined by the local standard of care). Serum creatinine < 2.0 x upper limit of normal. Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained prior to performing any study specific procedures. |
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E.4 | Principal exclusion criteria |
Patient should be excluded if they have unresolved chronic toxicity grade > 1 and related to prior therapy with sunitinib. History of cardiac disease: -Congestive heart failure NYHA (New York Heart Association) class > 2 -Active CAD (Coronary artery disease) or MI (Myocardial Infarction) more than 6 months prior to study entry is allowed) -Cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted) -Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management. Known history of HIV (Human immunodeficiency virus) infection or chronic Hepatitis B or C Active clinically serious infections (grade > 2 National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE Version 3.0)) Patients with seizure disorder requiring medication (such as steroids or anti-epileptics) Symptomatic metastatic brain or meningeal tumors unless the patient is > 6 months from definitive therapy, has a negative brain imaging study within 4 weeks of study entry and is clinically stable , with respect to CNS metastases, at the time of study entry. Also the patient must not be undergoing acute steroid therapy or taper (chronic steroid therapy is acceptable provided that the dose is stable for one month prior to and following screening radiographic studies) History of organ allograft Patients with evidence or history of bleeding diathesis or coagulopathy Patients undergoing renal dialysis Previous or concurrent cancer that is distinct in primary site or histology form the renal cell carcinoma EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, or superficial bladder tumors [Ta (Noninvasive tumor), Tis (Carcinoma in situ) & T1 (Tumor invades lamina propria)] or any cancer curatively treated > 3 years prior to study entry Any hemorrhage/bleeding event grade > 3 within 4 weeks of first dose of study drug Serious, non-healing wound, ulcer, or bone fracture Pregnant or breast-feeding patients. Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to 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 two weeks after the completion of trial. The investigator is requested to advise the patient how to achieve an adequate contraception. Substance abuse, medical, psychological or social conditions that may interfere with the patients participation in the study or evaluation of the study results Known or suspected allergy to the investigational agent or any agent given in association with this trial Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study Patients unable to swallow oral drugs Any malabsorption condition Excluded therapies and medications, previous and concomitant: Any anticancer therapy during the study Radiotherapy during study or within 3 weeks of start of study drug. (Palliative radiotherapy will be allowed as described in the Prior and concomitant Therapy section) Major surgery, or significant traumatic injury within 4 weeks of the first dose of study drug Autologous bone marrow transplant or stem cell rescue Investigational drug therapy outside of this trial during or within 4 weeks of study entry 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) Prior exposure to study drug |
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E.5 End points |
E.5.1 | Primary end point(s) |
After progression the dose of sorafenib can be increased in both arms. The primary end-point is the first PFS time which will be described using Kaplan-Meier curves for each treatment group. |
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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 | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Yes |
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 |
Sorafenib with or without interferon alfa-2a |
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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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
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 | No |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 7 |