| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Histologically confirmed operable oesophageal cancer |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10056104 |
| E.1.2 | Term | Squamous cell carcinoma of oesophagus |
| E.1.2 | System Organ Class | 100000004864 |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10056092 |
| E.1.2 | Term | Adenocarcinoma of oesophagus |
| E.1.2 | System Organ Class | 100000004864 |
|
| 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 |
| The principal research question is whether it is effective to treat oesophageal cancer patients eligible to receive chemo-radiotherapy with one of two differing radiosensitizer schedules [carboplatin/paclitaxel and oxaliplatin/capecitabine]. The aim of the trial is to select the most effective regime to take forward into a phase III trial in which pre-operative chemo-radiotherapy will be compared with chemotherapy in patients with locally advanced oesophageal cancer at high risk of R1 disease at surgery. |
|
| E.2.2 | Secondary objectives of the trial |
| 1. To assess the feasibility of recruiting patients into a pre-operative chemo-radiotherapy trial. This will be based on the recruitment figures over an 18 month period. 2. To determine whether the approach is safe by carefully monitoring any side-effects that the patients have and grading them according to a very specific set of toxicity criteria: the NCI Common Terminology Criteria for Adverse Events. Late toxicity assessment will also be monitored 6 months and 12 months. 3. To assess the efficacy of the trial by looking at overall survival rates. 4. In addition to the main research questions of the study, the trial will aim to standardise and improve radiotherapy treatment. This will involve a central review of PET/CT scans of patients randomised into NeoSCOPE to explore the accuracy and reproducibility of the radiotherapy planning. This will link into the POSITIVE study which also asks similar research questions. PET/CT scans are performed as part of standard practice |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
| Histologically confirmed operable oesophageal cancer (adenocarcinoma) Tumour must be staged as a T3, 4 or N1 (using TNM6 staging) or T3, T4a or N1-3 using TNM7 staging) Maximum disease (Tumour plus nodes) length 8 cm staged with EUS and CT/PET WHO performance status 0-1 Adequate haematological, renal, respiratory, cardiac and hepatic function The patient has provided written informed consent. |
|
| E.4 | Principal exclusion criteria |
| Histologically confirmed operable oesophageal cancer (squamous cell carcinoma) Uncontrolled angina pectoris, myocardial infarction within 6 months, heart failure, clinically significant uncontrolled cardiac arrhythmias, or any patient with a clinically significant abnormal ECG. Patients with any previous treatment for oesophageal carcinoma. Siewert type 3 oesophago-gastric tumours. T4 tumours invading contiguous structures other than diaphragm, crura or mediastinal pleura. Patients with disease in any of the following areas on the CT scan, EUS or other staging investigation: Evidence of other distant metastases. Para-aortic lymphadenopathy >1cm diameter on CT or >6mm diameter on EUS. Invasion of tracheo-bronchial tree, aorta, pericardium or lung. Lymphadenopathy encasing the coeliac axis (as described above, patients with single nodes lying anterior to the origin of the splenic artery and anterior to the origin of the coeliac axis are not excluded). Any patient with a single significant medical condition which is thought likely to compromise his or her ability to tolerate any of the above therapies. Specific contra-indications to surgery, chemotherapeutic agents (including known allergies to chemotherapy) or radiotherapy. Pregnant or lactating women and fertile women who will not be using adequate contraception during the trial. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary end point is to assess the efficacy of the treatment. This will be measured by assessing the pathological complete response rate (pCR) in patients undergoing resection following chemotherapy and chemo-radiotherapy treatment using standardised histological interpretation. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| The pCR of patients following surgery will be assessed through a central review of the histopathological work up of the resection specimen. As such, the trial endpoint will always be assessable. |
|
| E.5.2 | Secondary end point(s) |
| The secondary end points are feasibility, safety and efficacy. The feasbility will be determined by the number of patients recruited into the trial within 18 months. Early and late treament toxicities taken will be evaluated using CTCAE version 4. Efficacy will be assessed by measuring the circumferential resection margin (CRM) and median survival at 3 and 5 years. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Feasibility will be assessed at the end of 18 months of the trial being open to recruitment. Safety; SAEs are collected in real time. After 10 patients have competed trial treatment, SAEs and toxicities will be presented to the IDMC for a recommendation as to whether or not to continue recruitment. Toxicities will be coleected 30 and 90 after surgery and at 6 and 12 months post treatment. The efficacy will be assessed by looking at the CRM (circumferential resection margin) which is a measurement of how successful the surgery was in removing all traces of tumour. This will be assessed by looking at the removed tumour specimen. This will be reviewed centrally by Dr H Grabsch. |
|
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| 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 | No |
| 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 | 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.8.5 | 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 | No |
| E.8.7 | Trial has a data monitoring committee | No |
| 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 MHRA, the end of the trial is defined as the date of the last protocol treatment visit for the last participant undergoing protocol treatment. The protocol treatment phase will be followed by a followup period which will continue for one year after surgery.For the purposes of the Research Ethics Committee 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 | 2 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| 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 | 0 |
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