| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Small Bowel Adenocarcinoma |
|
| E.1.1.1 | Medical condition in easily understood language |
| Small Bowel Adenocarcinoma |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
To assess the efficacy (in terms of Disease free survival which is defined as time from randomisation to recurrence, development of a new primary or death from any cause) of observation against 24 weeks of adjuvant post-operative chemotherapy in resected stage I-IV small bowel adenocarcinoma and to assess the efficacy of 24 weeks of adjuvant post-operative fluoropyrimidine monotherapy versus fluoropyrimidine plus Oxaliplatin combination chemotherapy.
|
|
| E.2.2 | Secondary objectives of the trial |
| The secondary objectives are; overall survival, toxicity of chemotherapy, quality of life and the establishment of a central tissue bank for patients with small bowel adenocarcinoma |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. R0 resected stage I, II, III or IV small bowel adenocarcinoma
2. No evidence of residual or metastatic disease at laparotomy and on CT/MRI
imaging of chest, abdomen and pelvis.
3. Patients must be registered and randomised within 14 weeks of surgery and
commence chemotherapy within 16 weeks of surgery
4. ECOG Performance Status of 0 or 1
5. Absolute neutrophil count of ≥ 1.5 x10(9)/l
6. Platelet count ≥ 100 x 10 (9)/l
7. Haemoglobin ≥ 90 g/l (previous transfusion is allowed)
8. AST and ALT ≤ 2.5 x upper limit of normal (ULN). (At least one of ALT or
AST MUST be performed)
9. Creatinine clearance > 50 ml/min (calculated by Cockcroft Gault or Wright
equation) or measured by EDTA
10. Serum bilirubin ≤ 1.5 x ULN
11. Signed and dated informed consent indicating that the patient has
been informed of all the pertinent aspects of the trial prior to
enrolment.
12. Age ≥ 16 years
13. Willingness and ability to comply with scheduled visits, treatment plans
and laboratory tests and other trial procedures.
|
|
| E.4 | Principal exclusion criteria |
1. Non-adenocarcinoma histology of small bowel tumour which includes but is not
confined to lymphoma, GIST, carcinoid or other neuroendocrine tumour,
squamous carcinoma, melanoma or sarcoma.
2. Adenocarcinoma arising in the appendix or colorectum
3. Previous neo-adjuvant chemo(radio)therapy for small bowel adenocarcinoma
4. Clinically significant cardiovascular disease (i.e. active or < 12 months
since cerebrovascular accident, myocardial infarction, unstable angina, New
York Heart Association [NYHA] grade II or greater, congestive heart failure,
serious cardiac arrhythmia requiring medication, uncontrolled hypertension)
5. Pregnancy/lactation or of child bearing potential and not using medically
approved contraception. (Postmenopausal women must have been amenorrhoeic
for at least 12 months to be considered of non-childbearing potential)
6. Previous invasive or non-invasive malignancy except:
(i) Ductal carcinoma in situ of the breast where treatment consisted of
resection alone
(ii) cervical carcinoma in situ where treatment consisted of resection alone
(iii) basal call or squamous cell carcinoma where treatment consisted or
resection alone or radiotherapy
(iv) Superficial bladder carcinoma where treatment consisted of resection
alone or with a single installation of intravesical chemotherapy or with BCG
treatment
(v) other cancers where the patient has been disease free for at least 3
years and treatment was with curative intent
(vi) other cancers with very low potential for recurrence can be discussed
with the CI or his approved representative through the Glasgow CRUL CTU where
eligibility will be considered on an individual basis
7. Known or suspected dihydropyrimidine dehydrogenase (DPD) deficiency
8. Known untreated coeliac disease (may be enrolled if diet controlled),
untreated chronic inflammatory bowel disease or other cause of
malabsorption or intestinal obstruction
9. Grade ≥ 2 peripheral neuropathy
10. Administration of any investigational drug within 28 days or 5
half lives, whichever is longer, prior to receiving the first dose
of trial treatment
11. Previous hypersensitivity to platinum salts
12. Patients with clinically significant active infections, or any other serious
medical condition in which chemotherapy is contraindicated will be excluded
13. Patients with untreated vitamin B12 deficiency are excluded from receiving
folinic acid as part of their chemotherapy regimen. However, these patients
may be eligible for treatment with capecitabine fluoropyrimidine therapy,
where no folinic acid is administered as part of the treatment regimen
14. Patients with clinically significant sensorineural hearing impairment are
excluded from receiving oxaliplatin but will be eligible for the
fluoropyrimidine monotherapy provided as a clinician's choice for patients in
group 1 randomised to either observation or chemotherapy
15. Any patient receiving treatment with brivudine, sorivudine and analogues |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Disease free survival (defined as time from randomisation to recurrence, development of a new primary or death from any cause). |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Patients that are randomised to observation only will be seen 3 and 6 months post randomisation with all other follow up being the same as the treatment group.
Patients that are randomised to treatment will be seen prior to every chemotherapy treatment.
All patients will be seen 9, 12, 18, 24, 30 and 36 months post recruitment and then annually for a period of up to 7 years.
At all these time points patients will be accessed for recurrence, development or a new primary. These will be recorded on the CRF. If the patient has died this will also be recorded on the CRF |
|
| E.5.2 | Secondary end point(s) |
| Overall survival, cost-effectiveness, toxicity and molecular profiling of SBA |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Cost effectiveness will be accessed using the EQ-5D which will be completed at 3 and 6 months post randomisation and at every subsequent clinic visit.
Any toxicity the patients experiance will be collected at the time of clinic attendence on the CRF.
Patients can consent to their tumour being accessed and an additional blood sample being taken to allow for the molecular profiling of SBA. |
|
| 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 | Yes |
| 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) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| Observation (group 1 patients) |
|
| 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 | 21 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.5.1 | Number of sites anticipated in the EEA | 21 |
| 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 | No |
| 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
|
| For the purpose of the CTA the trial is deemed to have ended 30 days after the last patient remaining on treatment receives their last dose of study drug. For the purposes of the main REC approval the study end date is deemed to be the date of last data capture |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 9 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 1 |
| E.8.9.2 | In all countries concerned by the trial years | 9 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 1 |
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