E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Resectable pancreatic cancer |
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E.1.1.1 | Medical condition in easily understood language |
surgically removable pancreatic cancer |
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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 | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033602 |
E.1.2 | Term | Pancreatic adenocarcinoma resectable |
E.1.2 | System Organ Class | 100000004864 |
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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 if combination chemotherapy (gemcitabine and capecitabine), when used as adjuvant therapy in patients following resection for pancreatic adenocarcinoma, improves survival over adjuvant therapy using gemcitabine alone. |
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E.2.2 | Secondary objectives of the trial |
1. To compare the proportion of grade 3/4 toxicity across the treatment types. 2. To assess Quality of Life over time and treatment groups using the EORTC-C30 questionnaire. 3. To investigate and compare two year survival rates for the treatments. 4. To investigate and compare five year survival rates for the treatments. 5. To assess and compare relapse free survival (RFS).
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
There is an associated translational study for which, the objective is to collect and store frozen tissue, formalin fixed paraffin embedded tissue and plasma samples from patients in the trial. We shall aim to identify an expression profile in tumours associated with good or poor response to capecitabine or gemcitabine, allowing correlation with somatic and germline genetic features facilitating development of a practical molecular response signature. It is planned to undertake analysis of key enzymes and nucleoside transporters involved in gemcitabine and capecitabine metabolism and uptake (including polymorphisms).
The outcome is to identify a response profile with pancreatic cancer which will allow immediate improvement in treatment of this disease, facilitate identification of novel drug targets for patients who do not respond to present regimens and will act as a template for identification of similar profiles for other forms of cancer.
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E.3 | Principal inclusion criteria |
1. A) Patients who have undergone complete macroscopic resection for ductal adenocarcinoma of the pancreas (R0 or R1 resection) or B) Patients who have undergone complete macroscopic resection for peri-ampullary carcinoma (R0 or R1 resection). 2. Completion of all pre-operative investigations. 3. Histological confirmation of the primary diagnosis. 4. Histological examination of all resection margins. 5. Patients randomised ideally within 12 weeks of surgery, although case by case the CI will consider patients up to 14 weeks, and can begin treatment ideally within 14 weeks surgery 6. No evidence of malignant ascites, liver metastasis, spread to other distant abdominal organs, peritoneal metastasis, spread to extra-abdominal organs – CT (chest, abdomen, pelvis) scan within 3 months prior to randomisation.. 7. A WHO performance status <2 8. Creatinine clearance ≥ 50ml/min (according to Cockcroft and Gault, or equivalent value following local practice). 9. Fully recovered from the operation and fit to take part in the trial. 10. Able to attend for administration of the adjuvant therapy. 11. Able to attend for long-term follow-up. 12. Life expectancy > 3 months. 13. No previous or concurrent malignancy diagnoses (except curatively-treated basal cell carcinoma of skin, carcinoma in situ of cervix). 14. No serious medical or psychological condition precluding adjuvant treatment. 15. Fully informed written consent given. |
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E.4 | Principal exclusion criteria |
1. Use of neo-adjuvant chemotherapy or other concomitant chemotherapy. 2. Patients with pancreatic lymphoma. 3. Macroscopically remaining tumour (R2 resection). 4. Patients with TNM Stage IV disease. 5. Patients younger than 18 years. 6. Pregnancy. 7. New York Heart Association Classification Grade III or IV. 8. Previous chemotherapy. 9. All men or women of reproductive potential, unless using at least two contraceptive precautions, one of which must be a condom. 10. Patients with known malabsorption. 11. Patients with a baseline neutrophil count of <1.5 x 109/l. 12. Patients with a baseline platelet count of <100 x 109/l. 13. Patients with severe hepatic impairment. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Length of survival. This measure is length of survival defined as number of days between date of randomisation and date of death due to any cause (event) or date of last follow-up if patient is still alive at time of analysis (censored). |
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E.5.2 | Secondary end point(s) |
Pancreatic Ductal Adenocarcinoma: 1. Toxicity 2. Quality of life (assessed using the EORTC QLQ-C30 v3) 3. Two year survival 4. Five year survival 5. Relapse free survival (RFS)
Peri-Ampullary Carcinoma: 1. Toxicity 2. Quality of life 3. Four year survival 4. Relapse free survival (RFS) |
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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 | No |
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) | 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 | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 65 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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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 the trial is defined as the last follow up visit of the last patient randomised on to the trial. |
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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 | 11 |
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 | 11 |
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 |