E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Subjects with Locally Advanced Gastric Cancer or Cancer of the Gastroesophageal Junction |
|
E.1.1.1 | Medical condition in easily understood language |
Subjects with Locally Advanced Gastric Cancer or Cancer of the Gastroesophageal Junction |
|
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 | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10017758 |
E.1.2 | Term | Gastric cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10056267 |
E.1.2 | Term | Gastroesophageal cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
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 compare prevalence of pT3/T4 categories (in reference to UICC 2002 criteria, Appendix F) between subjects receiving panitumumab plus epirubicin, cisplatin and capecitabine (ECX) versus subjects treated with ECX chemotherapy alone. |
|
E.2.2 | Secondary objectives of the trial |
To compare prevalence of pN2/N3 categories between subjects receiving panitumumab plus epirubicin, cisplatin and capecitabine (ECX) versus subjects treated with ECX chemotherapy alone. To assess if the addition of panitumumab to ECX chemotherapy increases the histological complete and subtotal (< 10% residual tumour) response rates, R0 resection rate, progression-free survival time, time to relapse following surgery, time to treatment failure and overall survival in subjects with locally advanced gastric cancer or cancer of the gastroesophageal junction. To assess the overall safety and efficacy of ECX with or without panitumumab in this study population. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Competent to comprehend, sign, and date an IEC-approved informed consent form, written informed consent. - Of either gender and aged 18 years or more. - Diagnosed with histologically confirmed adenocarcinoma of the stomach or the gastroesophageal junction of Type I/II/III according to the classification of Siewert et al, 1996 (see Appendix E). - Stage uT/3 or 4 N0/+ and M0 (see Appendix F) disease evaluated by endoscopic ultrasound, spiral computed tomography of the chest, abdomen and pelvis and by laparoscopy in uT3/T4 tumors. - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 - Haematologic function, as follows (within 7 days of randomisation): - Leucocyte count ≥ 4,000/mm3 - Platelet count ≥100,000/mm3. - Haemoglobin ≥10 g/dl - Renal function, as follows (within seven days of randomisation): - Serum creatinine ≤ 1.5x of upper limit of normal (ULN) - Creatinine clearance > 60 ml/kg/min measured either by 24-h urine sampling or calculated by using the Cockgroft-Gault formula . - Hepatic function, as follows (within seven days of randomisation): - Aspartate aminotransferase (AST) ≤3 x ULN - Alanine aminotransferase (ALT) ≤3 x ULN. - Bilirubin ≤ 1.5 x ULN. - Metabolic function, as follows (within 7 days of randomisation): - Magnesium ≥ lower limit of normal. - Calcium ≥ lower limit of normal. - Subject is deemed a good candidate for surgery. |
|
E.4 | Principal exclusion criteria |
- Any metastatic disease. - Other malignant tumours less than five years old. Exceptions include basocellular carcinoma, in situ cancer of the cervix of the uterus, or any curatively-treated other malignancies without evidence of disease for more than five years. - Malignant ascites or pleural effusion. - Prior anti-EGFr antibody therapy (e.g. cetuximab) or treatment with small molecule EGFr tyrosine kinase inhibitors (e.g. erlotinib). - Prior chemotherapy, radiotherapy or antibody therapy for gastric cancer or cancer of the gastro-oesophageal junction. - Concomitant therapy with sorivudine or analogue compounds. - Known previous or ongoing abuse of narcotic drug, other medication or alcohol. - Significant cardiovascular disease including New York Heart Association (NYHA) grade II or greater congestive heart failure, peripheral arterial occlusive disease stage II or greater, symptomatic coronary heart disease, insufficiently treated arterial hypertension, unstable angina or myocardial infarction within 12 months before initiating study treatment or a history of ventricular arrhythmia. - History or evidence upon physical examination of CNS disease unless adequately treated, seizure not controlled with standard medical therapy, or history of stroke. - History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis on baseline chest CT scan. - Pre-existing polyneuropathy grade >1 according to the National Cancer Institute’s Common Terminology Criteria for Adverse Events (NCI CTCAE), except for loss of tendon reflex as the only symptom. - Treatment for systemic infection within 14 days before initiating study treatment. - Active inflammatory bowel disease, serious gastric ulceration or other bowel disease causing chronic diarrhoea (defined as > 4 loose stools per day). - Suspected or known dihydropyrimidine dehydrogenase deficiency (DPD). - Thrombosis or severe bleeding within six months prior to entry into the study (except for bleeding of the tumour before its surgical resection), evidence of bleeding diathesis or coagulopathy, or current or recent (within 10 days prior to initiation of study treatment) use of full-dose oral or parenteral anticoagulants for therapeutic purposes. - History of any medical condition that may increase the risks associated with study participation or may interfere with the interpretation of the study results. - Known positive test for human immunodeficiency virus infection, hepatitis C virus or chronic active hepatitis B infection. - Known allergy to the investigational product, to any of its excipients, to monoclonal antibodies, or to any of the components of the chemotherapy regimen. - Any co-morbid disease that would increase risk of toxicity. - Any kind of disorder that compromises the ability of the subject to give written informed consent and/or comply with the study procedures. - Any investigational agent or participation in another clinical trial within 30 days prior to randomisation. - Must not have had a major surgical procedure within 28 days of randomisation. - Subject who is pregnant or breast feeding. - Woman or man of childbearing potential not consenting to use adequate contraceptive precautions (intrauterine contraceptive device, contraceptive implants, injectables (hormonal depot), transdermal hormonal contraception (contraceptive patch), sexual abstinence or vasectomised partner) during the course of the study and for six months after the last study drug administration for women and men. Post-menopausal women must have been amenorrheic for at least 12 months to be considered of non-child-bearing potential. - Subject unwilling or unable to comply with study requirements. - Hearing impairment |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Frequencies of pT3/T4 categories (in reference to the UICC 7th Edition-2010 criteria) after surgery. Subjects prematurely discontinuing without a post-surgical tumour response assessment will be considered as non responders. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Frequencies of pN2/N3 categories after surgery Histological complete and subtotal response R0 resection rate Perioperative complication rate Postoperative mortality Progression free survival Time to relapse following surgery Time to treatment failure Overall survival time Toxicity/safety Translational research |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Frequencies of pN2/N3 categories after surgery -> after surgery Histological complete and subtotal response -> after surgery R0 resection rate -> after surgery Perioperative complication rate -> after surgery Postoperative mortality -> on event Progression free survival -> on event Time to relapse following surgery -> on event Time to treatment failure -> on event Overall survival time -> on event Toxicity/safety -> continuously Translational research -> after surgery |
|
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Standard chemotherapy with Epirubicin Cisplatin Capecitabine (ECX) |
|
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 | 25 |
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 | 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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
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 | 4 |
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 |