Investigation of the intra-tumoural concentration and activity of sorafenib in cutaneous schwannomas - Sorafenib in NF2

• Register: EUCTR
• Last refreshed on: 30 June 2019
• Main ID: EUCTR2011-001789-16-GB
• Date of registration: 17/05/2011
• Prospective Registration: Yes
• Primary sponsor: Plymouth Hospital NHS Trust
• Public title: Investigation of the intra-tumoural concentration and activity of sorafenib in cutaneous schwannomas - Sorafenib in NF2
• Scientific title: Investigation of the intra-tumoural concentration and activity of sorafenib in cutaneous schwannomas - Sorafenib in NF2
• Date of first enrolment: 26/08/2011
• Target sample size: 14
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-001789-16
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: no; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
(a)written informed consent (b)diagnosis of NF2 (c)over 18 years in age (d)presence of more at least two cutaneous schwannomas >1cm3 in area and accessible for biopsy (e)WHO/ECOG Performance Status 0 or 1 (f)adequate bone marrow function within 28 days prior to the baseline visit o WBC > 3.4x109/l o platelets > 99x109/l (g)adequate renal function within 28 days prior to the baseline visit o creatinine < 2.5 x upper limit of normal (h)adequate hepatic function within 28 days prior to the baseline visit o LFT < 1.5 x upper limit of normal o serum amylase < 1.5 x upper limit of normal o prothrombin (PT) or INR (International Normalized Ratio) and Prothrombin Time (PTT) < 1.5 x upper limit of normal (i)able to swallow tablets (j)patients with the potential for pregnancy or impregnating their partner must agree to use acceptable methods of birth control to avoid conception o female patients who are not using hormonal contraception must agree to employ two barrier methods of contraception (e.g. condom, diaphragm with spermicidal jelly) during the study and for 3 months following the end of their study participation o female patients who are using hormonal contraception must agree to use an additional barrier method (e.g. condom or diaphragm with spermicidal jelly) during the study and for 3 months following the end of study participation o post menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. k)Women of childbearing potential with a negative serum pregnancy test at screening and a negative urine pregnancy test at the baseline visit
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 0
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 0

Exclusion criteria:
(a)hypersensitivity to sorafenib or any of its excipients (b)cardiac arrhythmias requiring anti-arrhythmics (beta-blockers and digoxin are allowed) (c)symptomatic coronary artery disease or ischemia (d)myocardial infarction (MI) within the last six months; congestive cardiac failure > NYHA Class II (e)active clinically serious bacterial or fungal infections (f)known history of human immunodeficiency virus (HIV) infection or chronic hepatitis B or C (g)pregnant or breast-feeding (h)patients with uncontrolled hypertension (i)serious uncontrolled concomitant medical or psychiatric illness (j)concomitant medications o which have adverse interactions with sorafenib: rifampicin, ritonavir, ketoconazole, itraconazole and St John’s Wort o treatment with strong CYP3A4 inhibitors (e.g., erythromycin, ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, ritonavir, mibefradil) which has not been discontinued or switched to a different medication at least 2 weeks prior to starting the study drug. o Treatment with strong CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbitol, St John’s Wort), which has not been discontinued or switched to a different medication at least 2 weeks prior to starting the study drug. (k)Grade 3 or higher impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhoea, malabsorption syndrome) (l)history of acute pancreatitis within one year of study entry or medical history of chronic pancreatitis (m)history of another primary malignancy that is currently clinically significant or currently requires active intervention. (n)any other clinically significant medical or surgical condition which, according to the CI/PI’s discretion, should preclude participation (o)history of significant congenital or acquired bleeding disorder • patients taking warfarin or cytotoxic drugs


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Neurofibromatosis, type 2 (acoustic neurofibromatosis)
MedDRA version: 14.0 Level: LLT Classification code 10029271 Term: Neurofibromatosis, type 2 (acoustic neurofibromatosis) System Organ Class: 10010331 - Congenital, familial and genetic disorders

Intervention(s)

Trade Name: Nexavar
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: sorafenib (as tosylate)
Other descriptive name: Nexavar
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200mg-

Primary Outcome(s)

Primary end point(s): Target inhibition by sorafenib in cutaneous schwannoma biopsies

Secondary Objective: The secondary objectives of the study are: To assess whether target inhibition with oral sorafenib in plasma in NF2 patients with CS can act as a biomarker To analyze if tumour pain occurs after treatment with oral sorafenib in NF2 To identify early drug induced changes in the MRI scan (Manchester only)

Main Objective: The primary objectives of the study are: To measure steady-state plasma concentrations and intra-tumoural concentrations of sorafenib in cutaneous schwannomas after 11 days of oral dosing with sorafenib To investigate indices of molecular activity of sorafenib in tumour and blood, before and after treatment with sorafenib.

Secondary ID(s)

PenCTU/2011/CTIMP-005

Ethics review

Status: Approved
Approval date:
Contact: