A Phase II Trial of Sorafenib (a tyrosine kinase inhibitor) given orally twice daily in renal cancer patients with vHL syndrome - Oral Sorafenib in renal cancer patients with vHL syndrome

• Conditions: MedDRA version: 9.1Level: LLTClassification code 10047716Term: Von Hippel-Lindau disease; von Hippel Lindau syndrome (vHL) is a rare genetic disorder that causes a predisposition to develop multiple tumours, including renal, CNS and retinal tumours. vHL patients who have solid renal tumours (< or =2.4 cm) will require surgery to remove the renal tumours once they reach 2.5cm or greater. Disease-stabilising agents such as sorafenib could potentially delay or avoid the need for surgery.

• Registration Number: EUCTR2007-002132-29-GB
• Lead Sponsor: Oxford Radcliffe Hospitals NHS Trust

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-02-25
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

To be eligible, a patient must meet all of the following criteria:
1.Proven von Hippel Lindau syndrome by clinical, genetic or histological criteria.
2.Aged greater than 18 years.
3.ECOG performance status of 0-2
4.Lesions will be treated at a size below which surgery would be contemplated in order to prevent progression to larger lesions. Patients must have:
either a) Multiple renal lesions likely to lead to renal surgery. Lesions must be less than or equal to 2.4cm; OR b) Evidence on serial MRI scans for development of new lesions or progression of existing lesions. Note: other common sites of disease will be assessed by appropriate methodology at baseline (e.g. eyes – fluorescence angiography, Central Nervous System (brain/spinal cord) – MRI).

5.All patients must be using effective contraception. Women who are pregnant, nursing, or planning pregnancy within 6 months after the last treatment may not be included in the study (this includes men who plan to father a child within 6 months of the last treatment). Women of childbearing potential and all men who are (or become) sexually active must use adequate birth control measures (e.g. oral contraceptives, intrauterine device, barrier method with spermicide, or surgical sterilization) throughout the study and must continue such precautions for 6 months after receiving the last study agent infusion. All women of child-bearing age (i.e. unless postmenopausal, having had no menstrual period >=1 yr) must have a negative serum or urine pregnancy test performed within 7 days before the start of treatment.
6.Patient must give written, informed consent.
7.Haematological and biochemical indices within the following ranges (tests performed within one week before the patient goes on study) : Haemoglobin >or= 9.0 g/dl ; Platelet count > or =100 x 10 to the power of 9/L; Absolute Neutrophil count >or =1.5 x 10 to the power of 9/L; Serum bilirubin < or =1.5 x upper normal limit; Alanine amino-transferase (ALT) < or =2.5 x upper limit of normal (ULN) unless due to tumour in which case up to 5 x ULN is permissible; and Creatinine < or =180 µmol/L
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

A patient will not be eligible for the trial if any of the following criteria apply:
1.Radiotherapy (except for palliative reasons), major surgery, endocrine therapy, immunotherapy, chemotherapy or experimental therapy during four weeks (six weeks for nitrosureas and Mitomycin-C) prior to starting or during trial treatment.
2.Has had a myocardial infarction in the past twelve months, severe or unstable angina. Patients with a history of atherosclerotic coronary artery disease requiring coronary or peripheral artery bypass surgery may only be enrolled provided the surgery occurred at least two years prior to enrolment and after consultation with a cardiologist to ensure that the disease is stable.
3.Concurrent congestive heart failure or prior history of class III/ IV cardiac disease (New York Heart Association [NYHA. Cardiac arrhythmias requiring anti-arrhythmic therapy (beta-blockers or digoxin are permitted.
4.Uncontrolled hypertension, defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management.
5.Haemorrhage or bleeding event >CTCAE Grade 2 within 4 weeks prior to start of study drug. Taking therapeutic anticoagulation with vitamin K antagonists such as warfarin, or with heparins or heparinoids. Low dose warfarin (1 mg po qd) is permitted if the INR (International normalized ratio) is <=1.5. Low-dose aspirin permitted (<= 75 mg daily).
6.Has insulin-dependent diabetes mellitus, or has non-insulin dependent diabetes mellitus with clinical evidence of severe peripheral vascular disease or diabetic ulcers.
7.High medical risk due to active uncontrolled infection (> grade 2 NCI-CTCAE (National Cancer Institute Common Terminology for adverse Events) version 3.0) or non-malignant systemic disease (> grade 2 NCI-CTCAE version 3.0).
8.Co-existing or previous other malignancies unless in complete remission for not less than 5 years & excepting in situ carcinoma of the cervix or basal cell skin carcinoma.
9.History of HIV (Human immunodeficiency virus) infection or chronic hepatitis B or C.
10.Inability to swallow oral medication.
11.Known or suspected allergy to sorafenib or its constituents.
12.Other psychological, social or medical condition or a laboratory abnormality that the Investigator considers would make the patient a poor trial candidate or could interfere with protocol compliance or the interpretation of trial results.

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess stabilisation of disease or response of multiple primary renal cancers.;Secondary Objective: To assess the response of other sites of disease including retinal angiomata and spinal cerebellar haemangioma.<br>To assess the toxicity profile of Sorafenib in this group of patients<br>;Primary end point(s): To assess stabilisation of disease or response of multiple primary renal lesions.