E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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.
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E.2.2 | Secondary objectives of the trial |
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
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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
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E.4 | Principal 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
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E.5 End points |
E.5.1 | 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.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The ‘end of trial’ is defined as the last follow-up visit of the last patient on the trial. This will be the 80th patient. The last visit is planned to take place 6 months from the end of radiation therapy as per protocol. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |