| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Metastatic renal cell carcinoma (RCC) |
|
| 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 | 10050076 |
| E.1.2 | Term | Metastatic renal carcinoma |
|
| 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 |
| To assess the PFS of bevacizumab (10mg/kg i.v. every two weeks) in combination with a low dose of interferon alpha-2a (IFN) (3 MIU s.c. three times per week [t.i.w.]) administered until disease progression as first-line treatment of metastatic renal cell carcinoma. |
|
| E.2.2 | Secondary objectives of the trial |
| - To assess the efficacy of bevacizumab in combination with IFN 3MIU s.c. t.i.w., as measured by objective response rate (ORR) (as defined by RECIST criteria) and overall survival. - To make an historical comparison between the PFS, ORR and survival of bevacizumab in combination with IFN 3 MIU s.c. t.i.w., and the PFS, ORR and survival of bevacizumab in combination with IFN 9 MIU s.c. t.i.w. reported in the AVOREN trial (BO17705, the pivotal study for registration of bevacizumab in metastatic RCC). - To characterise the safety profile of bevacizumab in combination with IFN 3 MIU s.c. t.i.w, administered until disease progression in terms of, Grade 3-5 adverse event rate, overall adverse event rate and serious adverse event rate. - To make a historical comparison between the safety profile of bevacizumab in combination with IFN obtained in this study and the safety profile of bevacizumab in combination with IFN reported in the AVOREN trial. et al.... |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
| 1. Written informed consent (informed consent document to be approved by the institutions Independent Ethics Committee and consent obtained prior to any study-specific procedure) 2. Age >18 years 3. Able to comply with the protocol 4. Subject with histologically and/or cytologically confirmed, metastatic RCC, with majority (> 50%) of conventional clear-cell type is mandatory. (Subjects with predominantly papillary or sarcomatoid features, and subjects with chromophobe, oncocytoma, collecting duct tumours, Bellini tumours or transitional cell carcinoma are not allowed). Tumours of mixed histology should be categorized by the predominant cell type 5. Prior total nephrectomy for primary renal cell carcinoma. Partial nephrectomy is allowed only if the resection margins were clearly negative 6. At least one measurable or non-measurable lesion (as per RECIST criteria) 7. Eastern Cooperative Oncology Group (ECOG) PS status 0-2 (Karnofsky Performance Status >70) 8. Good or intermediate prognosis disease as defined by Motzer score 9. Life expectancy 12 weeks 10. Adequate haematological function: - Absolute neutrophil count (ANC) >1.5 x 109/L AND - Platelet count >100 x 109/L AND - Haemoglobin >8 g/dL (may be obtained by the use of erythropoietin or transfusion for anaemia). 11. Adequate liver function: - Total bilirubin <1.5 x upper limit of normal (ULN) AND - Aspartate aminotransferase (AST), alanine aminotransferase (ALT) <2.5 x ULN in patients without liver metastases; <5 x ULN in patients with liver metastases 12. Adequate renal function: - Serum creatinine 1.5 x ULN AND - Urine dipstick for proteinuria <2+. Patients with >2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate <1 g of protein in 24 hours 13. International normalised ratio (INR) (in absence of anticoagulation treatment) >1.5 within 7 days prior to enrolment. Anticoagulation is allowed if target INR is < 3 and if the patient is on a stable dose of anticoagulant (coumarin type, low molecular weight heparin (LMHW) or bivalirudin or argatroban) for > 2 weeks at time of enrolment 14. Female patients should not be pregnant or breast-feeding. Women of child bearing potential (i.e. a woman who is biologically capable of becoming pregnant) must have a negative serum pregnancy test within 7 days prior to enrolment into the study. If a serum pregnancy test is not performed within 7 days prior to the first dose of bevacizumab, a confirmatory urine test (within 7 days prior to the first dose of bevacizumab) is required. Patients (men and women) must agree to use medically accepted contraceptive methods with their partners throughout the study and for 90 days after the last dose of study treatment (bevacizumab or IFN, whichever is administered last) |
|
| E.4 | Principal exclusion criteria |
| 1. Prior systemic treatment for metastatic RCC disease (including neo-adjuvant therapy). Prior treatment with bevacizumab for any indication 2. Current or previously treated but non-stable (i.e. requiring changes in steroid dosage during the previous 4 weeks or receiving other therapy) central nervous system (CNS) metastases or spinal cord compression 3. Major surgery (incl. open biopsy) or radiation therapy within 28 days prior to enrolment. (Palliative radiotherapy to painful bone lesions is allowed within 14 days prior to enrolment). Subject must have recovered from prior surgery (> 28 days) and radiation (> 28 days - 14 days if palliative radiotherapy to painful bone lesions) 4. Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to enrolment 5. Significant cardiovascular disease defined as congestive heart failure (NYHA Class II, III, or IV), unstable angina pectoris, or myocardial infarction within 6 months prior to enrolment 6. Inadequately controlled hypertension (defined as a blood pressure of > 150 mmHg systolic and/or > 100 mmHg diastolic on medication), or any prior history of hypertensive crisis or hypertensive encephalopathy 7. History of stroke or transient ischemic attack within 6 months prior to enrolment 8. Significant vascular disease (e.g., aortic aneurysm, aortic dissection), or symptomatic peripheral vascular disease 9. Evidence or history of recurrent thromboembolism (>1 episode of deep venous thrombosis / peripheral embolism) during the past 2 years, bleeding diathesis or coagulopathy 10. Chronic daily intake of aspirin >325 mg/day or clopidogrel >75 mg/day 11. History of abdominal or tracheo-oesophageal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrolment 12. Serious, non-healing wound, ulcer, or bone fracture 13. Immuno-compromised patients, including known seropositivity for human immunodeficiency virus (HIV) 14. Chronic treatment with corticosteroids (dose of >10 mg/day methylprednisolone equivalent) excluding inhaled steroids or substitution therapy 15. Known hypersensitivity to any component of the investigational drugs or excipients 16. Current active second malignancy other than non-melanoma skin cancers and post-treatment for localised prostate cancer. Patients are not considered to have a currently active malignancy if they are in complete remission for >3 years prior to study 17. Any other significant medical illness or medically significant abnormal laboratory finding that would, in the investigator’s judgment, make the patient inappropriate for this study, or would increase the risk associated with the patients’ participation in the study 18. Treatment with any other investigational agent, or participation in another clinical trial within 28 days prior to enrolment |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficcay endpoint of this study is to assess the PFS of bevacizumab in combination with IFN 3 MIU s.c. three times per week until disease progression as first-line treatment of metastatic RCC |
|
| 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 | 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) | 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 | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | No |
| 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) | Information not present in EudraCT |
| E.8.2.2 | Placebo | Information not present in EudraCT |
| E.8.2.3 | Other | Information not present in EudraCT |
| 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 | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 45 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| 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
|
| la sperimentazione sara` conclusa dopo 2 anni dall`arruolamento dell`ultimo paziente o alla morte di tutti i pazienti, qualunque evento si verifichi per primo |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
Print
