E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Unresectable oesophageal and/or gastric cancer |
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E.1.1.1 | Medical condition in easily understood language |
Unresectable oesophagus (Gulet)and/or stomach cancer |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
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 see whether adding intravenous ω-3 FA emulsion to standard palliative chemotherapy (EOX) improves quality of life and/or prognosis, in patients with incurable gastric or oesophageal carcinoma. |
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E.2.2 | Secondary objectives of the trial |
• To determine the toxicity profile of the combination of omega-3 fish oil with standard EOX chemotherapy • To determine complete and partial response rates (as per RECIST v1.1 criteria) • To determine the feasibility of use of omega-3 fish oil with standard EOX chemotherapy • To collect tumour and blood samples for future translational work including investigating cytokine levels (leukotrienes B4, B5), Tumour necrosis factor-alpha, Interleukein-1, Iterleukein-2 and Interleukein-6; determining ω-3/6 ratios in cellular membranes of blood leucocytes, erythrocytes, plasma, platelets and tumour tissue • To determine quality of life, pain ratings and health status of patients using the EORTC QLQ-C30 questionnaire, brief pain inventory short form and dysphagia scores respectively • To determine the cost-effectiveness of the treatment by means of determination of NHS costs and quality of life using the EQ-5D questionnaire, enabling QALYs to be calculated |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Histologically confirmed gastric or oesophageal carcinoma (irrespective of subtype), deemed incurable as a result of standard staging investigations. • Measurable disease according to RECIST v1.1 criteria on CT within 4 weeks of study entry • WHO Performance status 0-2 • Aged >18 years • Able to give informed written consent • Life expectancy >12 weeks • Adequate hepatic and renal function documented within 7 days prior to treatment (estimated GFR>50ml/min, serum bilirubin <1.5x ULN; ALT or AST <2.5x ULN; ALP <3x ULN (in the absence of liver metastases). If liver metastases are present, serum transaminases <5x ULN are permitted.) • Adequate bone marrow function documented within 7 days (Haemoglobin ≥9g/dL, Platelets ≥100,000 cells/mm3, Neutrophil Count ≥1500 cells/mm3) • Women of childbearing age must have a negative pregnancy test (urine or serum) at commencement of treatment • Willing to use contraception if applicable • Willingness to comply with scheduled visits, treatment, laboratory test, and other aspects of the trial |
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E.4 | Principal exclusion criteria |
• Prior radical treatment within 6 months of relapse • Prior treatment with any systemic chemotherapy for metastatic disease • Prior adjuvant radio- or chemotherapy within 4 weeks of starting the study • Patients with locally advanced disease deemed suitable for radical chemo-radiotherapy • Known hyperlipidaemic state (use of a statin permissible) • Patients with known coagulation disorders • Hypersensitivity to fish, egg protein or to any of the active substances or constituents in the lipid emulsion • Any general contra-indications to infusion therapy – pulmonary oedema, hyperhydration, decompensated cardiac insufficiency • Any unstable medical conditions – uncontrolled diabetes mellitus, acute myocardial infarction, stroke, embolic disease, metabolic acidosis, sepsis, pancreatitis • Known HIV or hepatitis B or C carrier • Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with requirements of the protocol • History of malignancy other than gastric or oesophageal cancer, with the exception of curative treatment for skin cancer (other than melanoma) or in situ breast or cervical carcinoma, or those treated with curative intent for any other cancer with no evidence of disease for 5 years • Major surgical procedure or significant traumatic injury within 4 weeks of treatment • Cerebral metastases • History of interstitial lung disease (e.g., pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest CT scan • Known peripheral neuropathy > Grade 1 (absence of deep tendon reflexes as the sole neurological abnormality does not render the patient ineligible). • Lack of physical integrity of the upper gastro-intestinal tract, malabsorption syndrome, or inability to take oral medication (administration of capecitabine by naso-gastric or jejunostomy feeding tube is permitted). |
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E.5 End points |
E.5.1 | Primary end point(s) |
To determine the anti-tumour activity of the combination of omega-3 fish oil in combination with standard palliative EOX chemotherapy as measured by PFS. This is the time from enrolment to any disease progression and/or death, defined according to strict radiological criteria (Response Evaluation Criteria in Solid Tumours (RECIST v 1.1). Lesions will be compared to baseline measurements to assess progression. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary end point will be at 36 weeks from the commencement of the palliative treatment, each participant will have a CT scan at this time to evaluate for any progression, which will be used to assess for the progression free survival. |
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E.5.2 | Secondary end point(s) |
• Evaluation of toxicity, feasability and effect of fish oil infusion. • Overall survival (OS). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
•A safety review of toxicities will be performed after 10 and 21 patients have completed at least one cycle of chemotherapy and omega-3 fish oil treatment, If the review concludes that there is excess unacceptable toxicity then the safety committee may recommend that recruitment into the trial should cease. If the committee deem the trial safe to continue, recruitment will continue until a further 24 participants have been recruited (i.e. a total of 45 participants). •Time from enrolment to death for the overall survival. |
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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 | 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 | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
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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 | Yes |
E.8.2.3.1 | Comparator description |
Historical data of expected progression of discease within 6 months |
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E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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
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For the purposes of regulatory requirements the end of the trial is defined as the date of the last treatment visit for the last participant undergoing protocol treatment (week 24). The treatment phase will be followed by a follow up period which will continue for 1 year after the last participant completes protocol treatment. For the purposes of the Research Ethics Committee approval, the study end date is deemed to be the date of last data capture |
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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 | 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 |