SONATINA

A Phase II Multi-Centre Randomised Controlled Study Of Nelfinavir Addition to Radiotherapy Treatment In Neo-Adjuvant Therapy for Rectal Cancer.

EudraCT number: 2010-020621-40

Chief Investigator: Dr. Ricky Sharma

Sponsor: University of Oxford

Funded by: Oxford Biomedical Research Centre

The chief aim of the trial is to investigate the safety and the activity of the radiosensitising drug, Nelfinavir, administered before and during radiotherapy in patients with rectal carcinoma.

An additional aim of the study is to test the feasibility of using Tumour Cell Density (TCD) as a primary endpoint in clinical trials of radiosensitising agents administered with short-course radiotherapy (SCRT).

STUDY STATUS

Open to recruitment.
Target recruitment: 80
Current recruitment: 6 patients of initial safety cohort (October 2011)
Active sites: 1 (October 2011)

INCLUSION CRITERIA

Histologically proven adenocarcinoma of the rectum (tumour < 15 cm from anal verge).
Radiological evidence of M1 disease.
Treatment intent of SCRT is either down-sizing prior to delayed surgery (> 8 weeks) or palliation of symptoms from rectal cancer.
Colorectal Multidisciplinary Team (MDT) with surgical representation must document that patient is suitable for SCRT as primary treatment. In patients considered for systemic chemotherapy as standard (non-protocol) therapy prior to surgery, chemotherapy should commence > 14 days from the last fraction of SCRT. Patients should be imaged 8 weeks from the last fraction of radiotherapy and considered for pelvic surgery if sufficiently downsized.
Serum bilirubin < 3x normal.
AST or ALT < 3x normal.
Creatinine clearance > 50 ml/min.
WBC > 3.5/µl; platelets > 100.0/µl; haemoglobin > 10 g/dl.
Age > 18 years.
ECOG performance status 0-2.
Able to give written informed consent.
Willing and able to comply with the study procedures, including biopsy of the primary tumour 7 days from the last fraction of SCRT.

EXCLUSION CRITERIA

Operable primary tumour at time of study entry, for which the Colorectal MDT decide that surgery should be the primary treatment.
Previous pelvic radiotherapy.
Other experimental treatment ≤ 4 weeks prior to this study (including chemotherapy and immunotherapy).
History of other malignancy less than 2 years before the diagnosis of rectal cancer, excluding the following: Non-melanoma skin cancer, in situ carcinoma of the cervix treated surgically with curative intent, other malignant tumours that have been treated surgically and that have a disease-free survival of ≥10 years.
Recent (< 2 months) severe cardiac disease (e.g. arrhythmia, congestive heart failure, infarction).
Active infections (including chronic hepatitis type B or C and HIV infection if status known), severe immunologic defect, compromised bone marrow function.
Haemophilia A and B, phenylketonuria.
Known hypersensitivity to Nelfinavir or other HIV protease inhibitor.
Concurrent use of drugs with a narrow therapeutic window and which are substrates of cytochrome P450 (CYP) 3A (CYP3A4), that cannot be substituted by other drugs and that may not be discontinued during study treatment (e.g. phenobarbital, carbamazepine, phenytoin, terfenadine, astemizole, cisapride, amiodarone, quinidine, pimozide, triazolam, midazolam, ergotamines, rifampicin, herbal preparations that contain St John's Wort, Hypericum perforatum, omeprazole, simvastatin, lovastatin or atorvastatin, sildenafil or methadone).
Pregnant or breastfeeding.
If a woman of child bearing potential, unable or unwilling to use effective contraception during participation in the trial. Contraceptives that contain norethisterone and ethinylestradiol should be replaced by an alternative contraceptive or contraceptive method.
Major systemic co-morbidities preventing safe participation in the trial (this will be determined by the local PI).
Major psychiatric illness currently or within the past 12 months.
Any other condition or therapy that may represent a risk for the patient in the judgement of the treating physician or that could interfere with the aim of the study.

OpenClinica

Data submission for this trial is via electronic submission of data in OpenClinica. OpenClinica is the world's leading open source clinical trial software for electronic data capture and clinical data management. Information on how to use OpenClinica can be found on the OpenClinica Training page using the link below. It contains a user guide and instructional videos to show you how to use OpenClinica. After reviewing these if you have any other queries please contact a member of the trial team at OCTO.

» OpenClinica Training

Oncology Clinical Trials Office (OCTO)

Randomisation Service Mon-Fri 9-5 (UK Time):

UK Tel: 0800 389 1635, UK Fax: 0800 389 1629 (24hrs)

Non UK Tel: +44 (0)1865 617 014, Non UK Fax: +44 (0)1865 617 015 (24hrs) General

Enquiries: Tel: +44 (0)1865 617 000, Fax: +44 (0)1865 617 010

Email: SONATINA@octo-oxford.org.uk

Website: www.octo-oxford.org.uk