Dynamic contrast enhanced MRI (DCE-MRI) assessment of the vascular changes induced with bevacizumab alone and in combination with interferon-a in patients with advanced renal cell carcinoma. - DCE-MRI changes in tumour vaculature with Bevacizumab and Interferon in advanced RCC

Phase 1

• Conditions: Previously untreated metastatic (stage IV) or locally advanced (inoperable stage III), renal cell carcinoma; MedDRA version: 9.1Level: HLTClassification code 10038408Term: Renal cell carcinomas

• Registration Number: EUCTR2008-006414-19-GB
• Lead Sponsor: East and North Hertfordhsire NHS Trust

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-04-16
• Last Update Posted: 19 November 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 30

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

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To establish whether bevacizumab induced changes in DCE MRI vascular parameters are significantly enhanced by interferon-a<br>And if so:<br>To establish whether there is an IFN dose response in potentiating bevacizumab induced changes in DCE-MRI vascular parameters.<br>;Secondary Objective: - To correlate changes in DCE-MRI vascular parameters for each<br> treatment group with the following:<br>• progression free survival<br>• tumour response and changes in tumour size<br>• other surrogate biomarkers <br><br>- To assess the degree of change in baseline Ktrans within each arm of treatment<br>- To investigate changes in Diffusion and BOLD MRI and their correlation with other pharmacodynamic endpoints.<br>- To assess the efficacy and safety profile of Bevacizumab<br> monotherapy or in combination with low or standard doses of IFN<br>;Primary end point(s): DCE-MRI defined changes in Ktrans after 6 weeks of bevacizumab monotherapy or bevacizumab and low or standard dose IFN-a