inoperable rectal cancer
Conditions
Sponsors
The University of Oxford
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically proven adenocarcinoma of the rectum (tumour equal to or less than 15 cm from anal verge) 2. Radiological evidence of M1 disease 3. Treatment intent of SCRT is either down-sizing prior to delayed surgery equal to or greater than 8 weeks) or palliation of symptoms from rectal cancer 4. 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 equal to or greater than 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 5. Serum bilirubin equal to or less than 3x normal 6. AST or ALT equal to or less than 3x normal 7. Creatinine clearance >50 ml/min 8. WBC equal to or greater than 3.5/µl; platelets equal to or greater than 100,0/µl; haemoglobin equal to or greater than 10 g/dl 9. Age equal to or greater than 18 years 10. ECOG performance status 0-2 11. Able to give written informed consent 12. Willing and able to comply with the study procedures, including biopsy of the primary tumour 7 days from the last fraction of SCRT 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
Exclusion criteria: 1. Operable primary tumour at time of study entry, for which the Colorectal MDT decide that surgery should be the primary treatment 2. Previous pelvic radiotherapy 3. Other experimental treatment = 4 weeks prior to this study (including chemotherapy and immunotherapy) 4. 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 5. Recent (< 2 months) severe cardiac disease (e.g. arrhythmia, congestive heart failure, infarction) 6. Active infections (including chronic hepatitis type B or C and HIV infection if status known), severe immunologic defect, compromised bone marrow function 7. Haemophilia A and B, phenylketonuria 8. Known hypersensitivity to Nelfinavir or other HIV protease inhibitor 9. 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 Saint John's wort, Hypericum perforatum, omeprazole, simvastatin, lovastatin or atorvastatin, sildenafil or methadone) 10. Pregnant or breastfeeding 11. 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 12. Major systemic co-morbidities preventing safe participation in the trial (this will be determined by the local PI) 13. Major psychiatric illness currently or within the past 12 months 14. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the activity of the drug, Nelfinavir, when it is used to sensitise rectal cancer to radiotherapy treatment to try to make the radiotherapy more effective. ;Secondary Objective: Safety of Nelfinavir when combined with Short Course Radiotherapy (SCRT) assessed up to 6 months from last fraction of radiotherapy Radiological response of primary tumour at 8 weeks post-SCRT ;Primary end point(s): To investigate the safety and the activity of the radiosensitising drug, Nelfinavir, administered before and during radiotherapy in patients with rectal carcinoma. | — |
Countries
United Kingdom
Outcome results
None listed