Open-label, single-arm, phase II study of bevacizumab (AVASTIN®)in combination with low-dose interferon as first-line treatment ofnephrectomised patients with metastatic clear cell renal cell carcinoma

• Conditions: Metastatic renal cell carcinoma; MedDRA version: 9.1Level: LLTClassification code 10050513Term: Metastatic renal cell carcinoma

• Registration Number: EUCTR2007-006611-23-PT
• Lead Sponsor: F. Hoffmann-La Roche Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-11-03
• Last Update Posted: 16 October 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 150

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. 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 categorised 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) (see Appendix 2 for correspondence between ECOG PS and KPS)
8. Good or intermediate prognosis disease as defined by Motzer score
9. Life expectancy =12 weeks
10. Adequate haematological function:
a. Absolute neutrophil count (ANC) =1.5 x 10 9/L AND
b. Platelet count =100 x 10 9/L AND
c. Haemoglobin =8 g/dL (may be obtained by the use of erythropoietin or transfusion for anaemia)
11. Adequate liver function:
a. Total bilirubin <1.5 x upper limit of normal (ULN) AND
b. Asparagine 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:
a. Serum creatinine =1.5 x ULN AND
b. 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 bevacizumab and/or IFN (whichever is administered last).
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. 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 – see Appendix 3), 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 intraabdominal 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.

Study & Design

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