Clinical trial NCT01544790: Robot-assisted Thoraco-laparoscopic Esophagectomy Versus Open Transthoracic Esophagectomy
Official title: Robot-assisted Minimally Invasive Thoraco-laparoscopic Esophagectomy Versus Open Transthoracic Esophagectomy for Resectable Esophageal Cancer. The ROBOT-trial: a Monocenter Randomized Controlled Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Esophageal Carcinoma
Esophageal Cancer
Keywords: Esophageal carcinoma
Esophageal cancer
Robotic surgery
Esophagectomy
Minimally invasive
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
First posted: 2012-03-06
Enrollment: 112
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is the first randomized controlled trial designed to compare robot-assisted minimally invasive thoraco-laparoscopic esophagectomy with open transthoracic esophagectomy as surgical treatment for resectable esophageal cancer.

If our hypothesis is proved correct, robot-assisted minimally invasive thoraco-laparoscopic esophagectomy will result in a lower percentage of postoperative complications, lower blood loss, shorter hospital stay, but with at least similar oncologic outcomes and better postoperative quality of life compared with the open transthoracic esophagectomy (current standard).

Detailed description: Rationale: As stated in the 2010 revised Dutch esophageal carcinoma guidelines, the golden standard for surgical treatment of esophageal carcinoma is open transthoracic esophagectomy. Recent evidence suggests that robot-assisted thoraco-laparoscopic esophagectomy using the Da Vinci ® robot can provide an extensive resection, with possibly better or at least equal radical (R0) resection rates and an equal number of dissected lymph nodes. This is accompanied with markedly reduced blood loss and reduction of overall complications with shorter intensive care unit (ICU) and hospital stay. Therefore, the robot-assisted thoraco-laparoscopic esophagectomy is now at a stage that it should be compared to the current standard of care in a randomized controlled trial.

Objective: Evaluate the benefits, risks and costs of robot-assisted thoraco-laparoscopic esophagectomy as an alternative to open transthoracic esophagectomy as treatment for esophageal cancer.

Study design: Randomized controlled parallel-group superiority trial Study population: Patients (age ≥ 18 and ≤ 75 jaar) with histologically proven surgically resectable (cT1-4a, N0-3, M0) squamous cell carcinoma, adenocarcinoma or undifferentiated esophageal carcinoma of the intrathoracic esophagus with European Clinical Oncology Group (ECOG) status 0, 1 or 2.

Intervention: 112 patients will be randomly allocated to either A) robot-assisted thoraco-laparoscopic esophagectomy (n=56) or B) open transthoracic esophagectomy (n=56).

Patients will receive the following interventions:

Group A. Robot-assisted thoraco-laparoscopic esophagectomy, with gastric conduit formation.

Group B. Open transthoracic esophagectomy, with gastric conduit formation.

Main study parameters/endpoints: Primary outcome is the percentage of overall complications (Grade 2 and higher) as stated by the modified Clavien-Dindo classification (MCDC).

Secondary outcomes are individual components of the primary endpoint (major and minor complications), (in hospital) mortality within 30 and 60 days, R0 resections, operation related events, postoperative recovery, oncologic outcomes, cost-effectiveness and quality of life.

Follow-up: 60 months after randomization

Eligibility criteria: Inclusion Criteria:

* Histologically proven squamous cell carcinoma, adenocarcinoma or undifferentiated carcinoma of the intrathoracic esophagus.
* Surgical resectable (T1-4a, N0-3, M0)
* Age ≥ 18 and ≤ 75 years
* European Clinical Oncology Group (ECOG) performance status 0,1 or 2
* Written informed consent

Exclusion Criteria:

* Carcinoma of the cervical esophagus
* Carcinoma of the gastro-esophageal junction (GEJ) with major tumor in the gastric cardia (Siewert III)
* Prior thoracic surgery at the right hemithorax or thorax trauma (rationale: these patients will undergo open resection)

Primary outcomes:
measure: Postoperative complications modified Clavien-Dindo classification (MCDC) grade 2 and higher
timeFrame: Participants will be followed for the duration of hospital stay, an expected average of 2 weeks
Secondary outcomes:
measure: Individual components of the primary endpoint (major and minor complications)
timeFrame: Participants will be followed for the duration of hospital stay, an expected average of 2 weeks
measure: (In hospital) Mortality within 30 and 60 days
timeFrame: Participants will be followed for the duration of hospital stay, an expected average of 2 weeks and within 30 days or 60 days
measure: R0 resections (%)
timeFrame: Participants will be followed for the duration of hospital stay, an expected average of 2 weeks
measure: Operation related events
timeFrame: Day of surgery, up to 24 hours after surgery.
measure: Postoperative recovery
timeFrame: Participants will be followed for the duration of hospital stay, an expected average of 2 weeks
measure: Oncologic outcomes
timeFrame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months after surgery.
measure: Quality of life
timeFrame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months after surgery.
measure: Costs (euro)
timeFrame: 5 years follow up
Other outcomes:
Locations:
city: Utrecht
country: Netherlands
facility: UMC Utrecht
Study officials:
affiliation: UMC Utrecht, dept. of Surgery
name: Richard R. van Hillegersberg, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: van der Sluis PC, van der Horst S, May AM, Schippers C, Brosens LAA, Joore HCA, Kroese CC, Haj Mohammad N, Mook S, Vleggaar FP, Borel Rinkes IHM, Ruurda JP, van Hillegersberg R. Robot-assisted Minimally Invasive Thoracolaparoscopic Esophagectomy Versus Open Transthoracic Esophagectomy for Resectable Esophageal Cancer: A Randomized Controlled Trial. Ann Surg. 2019 Apr;269(4):621-630. doi: 10.1097/SLA.0000000000003031.
citation: van der Sluis PC, Ruurda JP, van der Horst S, Verhage RJ, Besselink MG, Prins MJ, Haverkamp L, Schippers C, Rinkes IH, Joore HC, Ten Kate FJ, Koffijberg H, Kroese CC, van Leeuwen MS, Lolkema MP, Reerink O, Schipper ME, Steenhagen E, Vleggaar FP, Voest EE, Siersema PD, van Hillegersberg R. Robot-assisted minimally invasive thoraco-laparoscopic esophagectomy versus open transthoracic esophagectomy for resectable esophageal cancer, a randomized controlled trial (ROBOT trial). Trials. 2012 Nov 30;13:230. doi: 10.1186/1745-6215-13-230.