E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Previously untreated metastatic (stage IV) or locally advanced (inoperable stage III), renal cell carcinoma |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10038408 |
E.1.2 | Term | Renal cell carcinomas |
|
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 |
To establish whether bevacizumab induced changes in DCE MRI vascular parameters are significantly enhanced by interferon-α And if so: To establish whether there is an IFN dose response in potentiating bevacizumab induced changes in DCE-MRI vascular parameters.
|
|
E.2.2 | Secondary objectives of the trial |
- To correlate changes in DCE-MRI vascular parameters for each treatment group with the following: • progression free survival • tumour response and changes in tumour size • other surrogate biomarkers
- To assess the degree of change in baseline Ktrans within each arm of treatment - To investigate changes in Diffusion and BOLD MRI and their correlation with other pharmacodynamic endpoints. - To assess the efficacy and safety profile of Bevacizumab monotherapy or in combination with low or standard doses of IFN
|
|
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 institution’s Independent Ethics Committee and consent obtained prior to any study-specific procedure) 2. Male or female subjects > 18 years 3. Patients with previously untreated metastatic (stage IV) or locally advanced (inoperable stage III), renal cell carcinoma 4. Subject with histologically and/or cytologically confirmed, advanced (stage IV) RCC, of which a majority component of conventional clear-cell type is mandatory. Tumours of mixed histology should be categorized by the predominant cell type. 5. Good or intermediate prognosis disease as defined by Motzer score. 6. RECIST measurable lesion(s), which must be amenable to DCE-MRI scanning 7. Life expectancy of at least 12 weeks 8. Eastern Co-operative Oncology Group (ECOG) performance status 0-2 9. Adequate haematological function: 10. Adequate liver function: 11. Adequate renal function: 12. International normalised ratio (INR) ≤1.5 within 7 days prior to enrolment. 13. Women of childbearing age must have a negative pregnancy test and must use adequate contraception during the treatment phase of the study and for 9 months afterwards. Women who wish to breastfeed are not eligible for the study
|
|
E.4 | Principal exclusion criteria |
1. Diagnosis of brain metastasis. 2. 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). 3. Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to enrolment 4. Significant cardiovascular disease defined as congestive heart failure (NYHA Class II, II, or IV), unstable angina pectoris, or myocardial infarction within 6 months prior to enrolment. 5. Inadequately controlled hypertension 6. History of stroke or transient ischemic attack within 6 months prior to enrolment 7. Significant vascular disease (e.g., aortic aneurysm, aortic dissection), or symptomatic peripheral vascular disease 8. Evidence or history of recurrent thromboembolism (>1 episode of DVT/PE) during the past 6 months, bleeding diathesis or coagulopathy 9. Chronic daily intake of aspirin >325 mg/day or clopidogrel >75 mg/day, or steroids (prednisone > 12.5 mg/day or dexamethasone > 2 mg/day). 10. History of abdominal or tracheo-oesophagel fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrolment 11. Serious, non-healing wound, ulcer, or bone fracture 12. Pregnant or breast feeding mothers 13. No contraindication to MRI scanning e.g. no history of claustrophobia, metal fragment implantation. 14. Current active second malignancy other than non-melanoma skin cancers and post-treatment for localized prostate cancer. Patients are not considered to have a currently active malignancy if they are in complete remission for >3 years prior to study 15. Patients with a history of allergic reactions to contrast agents 16. Patients with gross ascites 17. Seizure disorder requiring medication 18. HIV/Hep B/Hep C/ other infection >CTC 2; active clinically serious bacterial or fungal infections (> CTC 2) 19. Other investigational drug during trial or within 30 days 20. Any prior anti-angiogenic therapy within 6 months 21.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.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
DCE-MRI defined changes in Ktrans after 6 weeks of bevacizumab monotherapy or bevacizumab and low or standard dose IFN-α |
|
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 | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
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) | 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 | 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 |
same drugs at different doses |
|
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 | No |
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
|
last visit of the last subject undergoing trial |
|
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 | 0 |
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 |
E.8.9.2 | In all countries concerned by the trial days | 0 |