E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally Advanced, Potentially Resectable Adenocarcinoma of the Gastroesophageal Junction (GEJ)
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E.1.1.1 | Medical condition in easily understood language |
Locally advanced resectable gastric 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 | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10062878 |
E.1.2 | Term | Gastrooesophageal cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 determine if adding radiochemotherapy to neoadjuvant chemotherapy before undergoing oncologically adequate resection improves progression free survival of patients with resectable GEJ adenocarcinoma
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E.2.2 | Secondary objectives of the trial |
• To evaluate overall survival, including survival rates after 1, 3 and 5 years • To assess the R0 resection rate • To assess the number of lymph nodes harvested during surgery • To determine the site of tumor relapse • To assess the perioperative morbidity and mortality rate • To assess Safety and toxicity by NCI CTC criteria • To assess the quality of life (QoL) by using the EORTC QLQ-C30 and the esophagogastric module OG25 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Histologically proven, locally advanced and potentially resectable adenocarcinoma of the gastroesophageal junction (GEJ) (Siewert I- III) that is: cT3-4, any N, or cT2 N+ M0 according to AJCC 8th edition 2. Patients* must be candidates for potential curative resection as determined by the treating surgeon. 3. ECOG performance status 0-1 4. Age 18 years or above 5. Adequate hematologic function with absolute neutrophil count (ANC) ≥ 1.5 x 10^9/l, platelets ≥ 100 x 10^9/l and hemoglobin ≥ 9.0 mg/dl 6. INR <1.5 and aPTT<1.5 x upper limit of normal (ULN) within 7 days prior to randomization 7. Adequate liver function as measured by serum transaminases (ASAT, ALAT) ≤ 2.5 x ULN and total bilirubin ≤ 1.5 x ULN 8. Adequate renal function with serum creatinine ≤ 1.5 x ULN 9. QTc interval (Bazett**) ≤ 440 ms 10. Written informed consent obtained before randomization 11. Negative pregnancy test for women of childbearing potential within 7 days of commencing study treatment. Males and females of reproductive potential must agree to practice highly effective contraceptive measures*** during the study and for 6 months after the end of study treatment. Male patients must also agree to refrain from father a child during treatment and up to 6 months afterwards and additionally to use a condom during treatment period. Their female partner of childbearing potential must also agree to use an adequate contraceptive measure.
*There are no data that indicate special gender distribution. Therefore, patients will be enrolled in the study gender-independently. **formula for QTc interval calculation (Bazett) given in protocol ***highly effective (i.e. failure rate of <1% per year when used consistently and correctly) methods: intravaginal and transdermal combined (estrogen and progestogen containing) hormonal contraception; injectable and implantable progestogen-only hormonal contraception; intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; vasectomised partner; sexual abstinence (complete abstinence is defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments). |
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E.4 | Principal exclusion criteria |
1. Evidence of metastatic disease (exclusion of distant metastasis by CT of thorax and abdomen, bone scan or MRI [if osseous lesions are suspected due to clinical signs]) 2. Past or current history (within the last 5 years prior to treatment start) of other malignancies. Patients with curatively treated basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix are eligible 3. Evidence of peripheral sensory neuropathy > grade 1 according to CTCAE version 4.03 (see appendix) 4. Patients with other significant underlying medical conditions that may be aggravated by the study treatment or are not controlled 5. Pregnant or lactating females 6. Patients medically unfit for chemotherapy and radiotherapy 7. Patients receiving any immunotherapy, cytotoxic chemotherapy or radiotherapy other than defined by the protocol. The participation in another clinical trial with the use of investigational agents, chemotherapy or radiotherapy during the trial is not permitted 8. Known hypersensitivity against 5-FU, folinic acid, oxaliplatin or docetaxel 9. Other known contraindications against 5-FU, folinic acid, oxaliplatin or docetaxel 10. Clinically significant active coronary heart disease, cardiomyopathy or congestive heart failure, NYHA III-IV 11. Clinically significant valvular defect 12. Other severe internal disease or acute infection 13. Peripheral polyneuropathy > NCI Grade II according to CTCAE version 4.03 14. Chronic inflammatory bowel disease |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression-free survival (PFS) due to the addition of preoperative radiochemotherapy compared to perioperative chemotherapy alone in patients undergoing oncologically adequate surgery in the treatment of resectable GEJ adenocarcinoma |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Overall survival, including survival rates after 1, 3 and 5 years R0 resection rate Number of harvested lymph nodes Site of tumor relapse Perioperative morbidity and mortality rate Satefy and toxicity by NCI CTC criteria Quality of life (QoL) by using the EORTC QLQ-C30 and the esophagogastric module OG25 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Overall survival, including survival rates: after 1, 3 and 5 years R0 resection rate: after surgery Number of harvested lymph nodes: after surgery Site of tumor relapse. Perioperative morbidity and mortality rate: after surgery Satefy and toxicity by NCI CTC criteria Quality of life (QoL) by using the EORTC QLQ-C30 and the esophagogastric module OG25 |
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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) | 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 | 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) | 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 | 40 |
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
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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 | 8 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |