Background
Methods / design
Aim of the study
Study design
Study population
Data category | Information |
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Primary registry and trial identifying number | |
Date of registration in primary registry | 13th March, 2020 |
Secondary identifying numbers | ROBOT2 trial, 2019–14,049 |
Source of material support | Intuitive Surgical Inc. |
Primary sponsor | Intuitive Surgical Inc. |
Contact for public queries | ET, PPG [email address] |
Contact for scientific queries | ET, PPG University Medical Center Mainz, Mainz, Germany |
Public title | RAMIE Versus MIE for Resectable Esophageal Cancer, a Randomized Controlled Trial (ROBOT-2 Trial). |
Scientific title | Randomized controlled parallel-group, superiority trial comparing RAMIE to MIE with intrathoracic anastomosis (Ivor-Lewis) in patients with resectable intrathoracic esophageal adenocarcinoma or adenocarcinoma of the gastroesophageal junction in the Western World. |
Countries of recruitment | Germany, The Netherlands, Switzerland |
Health condition(s) or problem(s) studied | Experimental: Robotic assisted minimally invasive esophagectomy (RAMIE) for esophageal cancer |
Intervention(s) | Active comparator: Minimally invasive esophagectomy (MIE) for esophageal cancer |
Key inclusion and exclusion criteria | Ages eligible for study: 18–90 years of age Sexes eligible for study: both Accepts healthy volunteers: no Inclusion criteria: Histologically proven adenocarcinoma of the intrathoracic esophagus and gastroesophageal junction (including Siewert types I and II) Surgically resectable (T1-4a, N0–3, M0) European Clinical Oncology Group (ECOG) performance status 0,1 or 2 Written informed consent Exclusion criteria: Esophageal squamous cell carcinoma Carcinoma of the cervical esophagus Carcinoma of the esophageal junction (GEJ) with the main part of the tumor in the gastric cardia (Siewert type III) Prior thoracic surgery at the right hemithorax or thoracic trauma |
Study type | Interventional Allocation: randomized; Intervention model: parallel assignment; Masking: single (outcomes assessor); Masking description: anonymous cases Primary purpose: treatment |
Date of first enrolment | 18th January 2021 |
Target sample size | 218 |
Recruitment status | Recruiting |
Primary outcome(s) | Total number of dissected lymph nodes in the resection specimen according to the TIGER classification |
Key secondary outcomes | 1.Postoperative complications [Time Frame: Operation date till date of discharge until 52 weeks postoperatively] 2.Length of intensive care unit (ICU) and hospital stay [Time Frame: Operation date till date of discharge until 52 weeks postoperatively] 3.In hospital mortality (IHM) [Time Frame: Hospital admission period up to 90 days postoperatively] 30, 60 and 90 day mortality 4.Pathology results [Time Frame: Up to 2 weeks postoperatively] Radical resection (R0 and R1) 5.Survival [Time Frame: 5 years postoperatively] Overall and disease free survival (2,3 and 5 year) 6.Operation statistics [Time Frame: day of operation] Operating time (thoracic, abdominal and total), blood loss, intraoperative complications 7.Postoperative pain [Time Frame: Before operation (baseline), daily during admission in the first 14 days, postoperatively: 6 weeks, 6 months and yearly post-operatively up to 5 years] Postoperative pain scores on a visual analogue scale (VAS) 8.Cost analysis [Time Frame: date of operation until 1 year postoperatively] Cost analysis 9.Surgeons fatigue [Time Frame: Day of operation] Surgeons fatigue directly after Operation assessed by Psychomotor Vigilance tests (PVT) before and after esophagectomy 10.Quality of life after esophagectomy [Time Frame: Before operation (baseline), at discharge, postoperatively: 6 weeks, 6 months and yearly up to 5 years post-operatively] Quality of life assessed by questionnaire European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 11.Postoperative Recovery [Time Frame: 14 days postoperatively] Dutch discharge criteria (removal of thoracic tubes, no requirement of intravenous fluid resuscitation, tolerance for solid oral intake, the ability to mobilize independently and adequate pain control with oral analgesics) 12.Quality of life after esophagectomy [Time Frame: Before operation (baseline), at discharge, postoperatively: 6 weeks, 6 months and yearly up to 5 years post-operatively] Quality of life assessed by questionnaire European Organisation for Research and Treatment of Cancer (EORTC OES18) 13.Quality of life after esophagectomy [Time Frame: Before operation (baseline), at discharge, postoperatively: 6 weeks, 6 months and yearly up to 5 years post-operatively] Quality of life assessed by questionnaire Short Form (SF)-36 14.Quality of life after esophagectomy [Time Frame: Before operation (baseline), at discharge, postoperatively: 6 weeks, 6 months and yearly up to 5 years post-operatively] Quality of life assessed by questionnaire EuroQol (EQ)-5D |
Inclusion criteria | |
- Histologically proven adenocarcinoma of the mid or distal intrathoracic esophagus or adenocarcinoma of the GE junction | |
- Eligible for Ivor-Lewis esophagectomy | |
- Surgically resectable (T1-4a, N0–3, M0) | |
- Age ≥ 18 and ≤ 90 years | |
- European Clinical Oncology Group (ECOG) performance status 0,1 or 2 | |
- Written informed consent | |
Exclusion criteria | |
- Carcinoma of the cervical or proximal thoracic esophagus | |
- Carcinoma of the gastro-esophageal junction (GEJ) with the bulk of the tumor in the gastric cardia | |
- Prior thoracic surgery at the right hemithorax or thoracic trauma |
Assessment | 30 days after OP | 6 weeks after OP | 90 days after OP | 6 months after OP | 12 months after OP | 18 months after OP | 24 months after OP | 36 months after OP | 48 months after OP | 60 months after OP |
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QoL Questionnaires | x | x | x | x | x | x | x | |||
Clinical examination | x | x | x | x | x | x | x | x | x | |
VAS for pain | x | x | x | x | x | x | x |
Study protocol
Neoadjuvant and perioperative treatment
Surgery
Surgical procedure: RAMIE
Surgical procedure: MIE
Primary endpoint
Secondary outcomes include
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Overall postoperative complications according to the modified Clavien Dindo classification (MCDC grade I-V)) [26] and definitions stated by the Esophagectomy Complications Consensus Group (ECCG) [27]. Postoperative complications include: anastomotic leakage, mediastinitis, gastric conduit necrosis, chylothorax and recurrent laryngeal nerve injury, delayed gastric emptying, pulmonary complications (pneumonia, pneumothorax, pulmonary embolus, acute respiratory distress syndrome (ARDS)), cardiac complications (atrial fibrillation, cardiac asthma, myocardial infarction) and postoperative bleeding. The incidence of incisional hernias and diaphragmatic hernias will be recorded.
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Length of ICU-MCU stay (days), length of hospital stay (days)
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In hospital mortality (IHM) and mortality within 30, 60 and 90 days postoperatively will be reported. For all patients, the cause of death will be noted.
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Pathology results: The pathology report contains the following parameters: site and size of tumor, type and gradation, extension in the esophageal wall, margins of the resection, extent of resection (R0, R1 or R2), lymph node status with the total number of lymph nodes and the number of positive lymph nodes per lymph node station (TNM 8 and TIGER) [25]. A standard protocol will be used in all centers.
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Overall and disease-free survival (2, 3 and 5 years). Overall survival (OS) was calculated from the date of surgery to the date of death or last follow-up. Disease free survival was calculated from the date of surgery to recurrence or death related to disease and/or treatment or last date of follow-up.
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Operation time is defined as time from incision until closure (minutes) for both the thoracic and the abdominal phase of the procedure. Unexpected events and complications occurring during the operation will be recorded (e.g. hemorrhage requiring transfusion, perforation of other organs) as well as blood loss during operation (ml, per phase). In case of conversion to thoracotomy or laparotomy the reason for conversion has to be explained (absolute numbers/percentage).
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Visual Analogue Scale (VAS) for pain will be noted at following times: pre-operatively and the first 14 days after surgery and at fixed intervals during follow up (6 weeks, 6 months and yearly post-operatively up to 5 years).
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Quality of life questionnaires (QoL) will be required at following times: SF-36, EORTC QLQ-C30 (German), EORTC OES18 (German) and EQ-5D (Appendix 1 & 2) pre-operative < 5 days and 6 weeks, 3 months, 6 months and yearly up to 5 years post-operatively [30].
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Postoperative functional recovery within 14 days and within the period of hospitalization. Postoperative recovery is defined as: removal of thoracic tubes, no requirement of intravenous fluid resuscitation, tolerance for solid oral intake, the ability to mobilize independently and adequate pain control with oral analgesics. All items will be assessed daily.
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Cost analysis: The approach for the cost-analysis is comparing actual direct medical costs incurred with both strategies up until 5 years after the operation. Costs estimates will be based on the recorded volumes and unit costs associated with both procedures. This includes the costs of operation rooms, hospital and ICU stay, costs associated with complications and re-operations.
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Surgeons fatigue assessed by Psychomotor Vigilance tests (PVT) before and after esophagectomy.
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Conversion