RAMIE vs OTE for Esophageal Cancer

(RAMIE vs OTE Trial)

Overseen By Yogita S. Patel

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: St. Joseph's Healthcare Hamilton

Disqualifiers: Pregnancy, Stage IV cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new surgical method for esophageal cancer using robotic technology. The aim is to determine if Robotic Assisted Minimally Invasive Esophagectomy (RAMIE), which employs advanced robotic tools, can serve as a safer and more effective alternative to the traditional Open Transthoracic Esophagectomy (OTE). RAMIE may provide benefits such as shorter recovery times and fewer complications. Individuals with Stage I, II, or III esophageal cancer considering surgery might be suitable candidates for this trial. As an unphased trial, it offers patients the chance to explore innovative surgical options that could enhance recovery and outcomes.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What prior data suggests that RAMIE is safe for esophageal cancer surgery?

Research has shown that Robotic Assisted Minimally Invasive Esophagectomy (RAMIE) is generally safe. Studies have found that RAMIE often results in fewer complications compared to traditional open surgery. For example, patients undergoing RAMIE typically experience fewer postoperative issues and shorter hospital stays. However, some risks exist, such as potential injuries to the laryngeal nerve, occurring in about 33-36% of cases. This nerve, located near the voice box, can affect speech if injured.

RAMIE requires significant practice for surgeons to master. Despite this, RAMIE remains a promising option for treating esophageal cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Robotic Assisted Minimally Invasive Esophagectomy (RAMIE) because it offers a less invasive option for esophageal cancer surgery compared to the traditional Open Transthoracic Esophagectomy (OTE). RAMIE uses a robotic approach that requires fewer incisions, which can lead to a quicker recovery and less postoperative pain for patients. Additionally, the use of near-infrared fluorescence (NIF) with indocyanine green (ICG) dye allows surgeons to better visualize and assess the blood supply to the gastric conduit, potentially reducing complications like anastomotic leaks. This innovative approach could improve patient outcomes and enhance the overall safety of esophageal cancer surgeries.

What evidence suggests that this trial's treatments could be effective for esophageal cancer?

This trial will compare Robotic Assisted Minimally Invasive Esophagectomy (RAMIE) with Open Transthoracic Esophagectomy (OTE) for esophageal cancer. Research has shown that RAMIE can be safer than traditional open surgery for the esophagus. Studies have found that RAMIE often results in fewer complications and shorter hospital stays. The 3D camera used in RAMIE provides surgeons with a better view, enhancing surgical precision. This precision helps minimize damage to the chest or abdomen during the procedure. Additionally, RAMIE allows doctors to check blood flow to the stomach, potentially reducing the risk of leaks after surgery. Early reports suggest that RAMIE is a promising option compared to the traditional method for esophageal cancer surgery. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults with Stage I, II, or III esophageal cancer who are eligible for surgery. It's not open to pregnant or breastfeeding women, those not using birth control, people allergic to ICG/sodium iodide/iodine, or anyone unsuitable for minimally invasive surgery.

Inclusion Criteria

My surgeon has approved me for a less invasive surgery.

My esophageal cancer is in an early stage and I am a candidate for surgery.

Exclusion Criteria

I am not pregnant, breastfeeding, and if able to bear children, I am using effective birth control.

Hypersensitivity or allergy to ICG, sodium iodide, or iodine

My esophageal cancer is in stage IV.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase A: Learning Curve

40 patients undergo NIF-guided RAMIE using ICG dye to gain proficiency

Varies per patient

Phase B: Randomized Controlled Feasibility Trial

54 patients are randomized to either NIF-guided RAMIE using ICG dye or OTE

Varies per patient

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Postoperative Day 1, 3-Weeks Postoperative, 12-Weeks Postoperative

What Are the Treatments Tested in This Trial?

Interventions

• Open Transthoracic Esophagectomy (OTE)
• Robotic Assisted Minimally Invasive Esophagectomy (RAMIE)

Trial Overview

The study compares two surgical methods for esophageal cancer: a new robotic-assisted technique (RAMIE) and the standard open surgery (OTE). RAMIE uses advanced robotics aiming to reduce complications and recovery time.

How Is the Trial Designed?

Group I: NIF-Guided RAMIE using ICG Dye (Experimental Arm) Experimental Treatment 1 Intervention

The patient will undergo NIF-guided RAMIE using ICG dye using the standard Ivor-Lewis approach. This will be a two-stage operation involving a first stage through a 5-port robotic approach through the abdomen to achieve a proximal gastrectomy and D2 nodal dissection. A feeding jejunostomy would not be inserted, as per the enhanced recovery pathway for esophagectomy. In addition, the vascularization of the conduit can be confirmed using the near-infrared camera of the robot with the ICG dye. The second stage of the operation will involve a 4-port robotic approach through the right chest to achieve thoracic nodal dissection, esophagectomy, and a hand-sewn anastomosis between the residual esophagus and the gastric conduit at the level of the azygous vein. During this second stage of the operation, NIF with ICG dye will be used to visualize the vascular supply of the gastric conduit, and assess the gastric conduit for any perfusions to potentially reduce anastomotic leaks.

Group II: Open Transthoracic Esophagectomy (OTE) Active Control 1 Intervention

The patient will undergo OTE using the standard Ivor-Lewis approach. This is a two-stage operation involving a first stage through laparotomy, proximal gastrectomy, D2 nodal dissection, and insertion of feeding jejunostomy. The second stage of the operation will involve a right thoracotomy, thoracic nodal dissection, esophagectomy, and a stapled anastomosis between the residual esophagus and the gastric conduit at the level of the azygous vein.

Open Transthoracic Esophagectomy (OTE) is already approved in Canada, European Union, United States for the following indications:

Approved in Canada as Open Transthoracic Esophagectomy for:

• Esophageal cancer

Approved in European Union as Open Transthoracic Esophagectomy for:

• Esophageal cancer

Approved in United States as Open Transthoracic Esophagectomy for:

• Esophageal cancer

Who Is Running the Clinical Trial?

St. Joseph's Healthcare Hamilton

Lead Sponsor

Trials

203

Recruited

26,900+

McMaster University

Collaborator

Trials

936

Recruited

2,630,000+

Published Research Related to This Trial

In a study of 170 patients with esophageal cancer, those who underwent robotic-assisted minimally invasive esophagectomy (RAMIE) reported better quality of life (QOL) scores compared to those who had open esophagectomy (OE) after 2 years, particularly in esophageal symptoms and emotional well-being.

Patients in the RAMIE group experienced significantly lower pain severity compared to the OE group, indicating that RAMIE may offer a safer and more comfortable recovery experience for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-Year Quality of Life Outcomes After Robotic-Assisted Minimally Invasive and Open Esophagectomy. Vimolratana, M., Sarkaria, IS., Goldman, DA., et al.[2022]

Robot-assisted minimally invasive thoraco-laparoscopic esophagectomy (RAMIE) for esophageal cancer resulted in a high rate of successful radical resections (95%) and adequate lymph node removal, indicating its oncological effectiveness.

With a median follow-up of 58 months, RAMIE demonstrated a 5-year overall survival rate of 42% and a low local recurrence rate, suggesting it provides good long-term control of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oncologic Long-Term Results of Robot-Assisted Minimally Invasive Thoraco-Laparoscopic Esophagectomy with Two-Field Lymphadenectomy for Esophageal Cancer. van der Sluis, PC., Ruurda, JP., Verhage, RJ., et al.[2022]

In a study of 9,217 patients with esophageal cancer, robotic-assisted minimally invasive esophagectomy (RAMIE) showed a trend toward higher 30-day mortality compared to open esophagectomy (OE) and minimally invasive esophagectomy (MIE), although this was not statistically significant in matched cohorts.

There were no significant differences in long-term survival among patients undergoing RAMIE, MIE, or OE, suggesting that the surgeon's experience may play a more critical role in patient outcomes than the type of surgical approach used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival After Esophagectomy: A Propensity-Matched Study of Different Surgical Approaches. Weksler, B., Sullivan, JL.[2022]

Minimally invasive esophagectomy (MIE) and robotic-assisted minimally invasive esophagectomy (RAMIE) show comparable overall survival rates to open esophagectomy (OE), with no significant differences in mortality rates at 30 and 90 days, indicating their safety and efficacy as surgical options for esophageal cancer.

Both MIE and RAMIE resulted in shorter hospital stays and higher lymph node yields compared to OE, suggesting that these minimally invasive techniques may enhance postoperative recovery and provide better staging information.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does the Approach Matter? Comparing Survival in Robotic, Minimally Invasive, and Open Esophagectomies. Espinoza-Mercado, F., Imai, TA., Borgella, JD., et al.[2019]

In a study of 226 patients with esophageal squamous cell carcinoma (ESCC), overexpression of the EP2 receptor was found in 43.4% of cases and was linked to deeper tumor invasion and worse overall survival rates.

For patients with early-stage ESCC (T1-3N0M0), EP2 overexpression was identified as an independent prognostic factor for poor survival, highlighting its potential role in assessing patient risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic role of PGE2 receptor EP2 in esophageal squamous cell carcinoma. Kuo, KT., Wang, HW., Chou, TY., et al.[2022]

In a study of 85 patients, it was found that the expression of COX-2 and the EP2 receptor increased significantly in the progression from Barrett's metaplasia to oesophageal adenocarcinoma, indicating their potential role in cancer development.

The EP4 receptor was also found to be elevated in oesophageal adenocarcinoma, suggesting that both EP2 and EP4 could be targeted for prevention or treatment of Barrett's-associated adenocarcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostaglandin EP2 receptor expression is increased in Barrett's oesophagus and oesophageal adenocarcinoma. Jiménez, P., Piazuelo, E., Cebrian, C., et al.[2010]

In a study using the OE33 esophageal adenocarcinoma cell line, COX-2 was found to be the main source of PGE(2) production, and inhibiting COX-2 significantly reduced cell proliferation, indicating its potential as a therapeutic target.

The research identified that blocking specific PGE(2) receptors (EP(1) and EP(4)) inhibited cell migration and reduced the effects of PGE(2) on cell behavior, suggesting that EP receptor antagonists could be a promising strategy for treating esophageal adenocarcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of selective PGE2 receptor antagonists in esophageal adenocarcinoma cells derived from Barrett's esophagus. Piazuelo, E., Jiménez, P., Strunk, M., et al.[2013]

Inhibition of 12-lipoxygenase (12-LOX) in esophageal squamous cell carcinoma (ESCC) cells reduced the levels of epithelial-mesenchymal transition (EMT) and decreased the cells' ability to migrate and invade, suggesting that 12-LOX plays a critical role in tumor progression.

The study found that higher levels of 12-LOX expression were associated with poorer overall survival in ESCC patients, indicating that 12-LOX could serve as a valuable biomarker for predicting patient prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

12-lipoxygenase promotes tumor progress by TGF-β1-mediated epithelial to mesenchymal transition and predicts poor prognosis in esophageal squamous cell carcinoma. Qu, Y., Wen, Z., Mi, S., et al.[2022]

In a follow-up study of the ROBOT trial involving 112 patients with esophageal cancer, robotic-assisted minimally invasive esophagectomy (RAMIE) showed comparable 5-year overall survival rates (41%) and disease-free survival rates (42%) to open transthoracic esophagectomy (OTE) (40% overall survival, 43% disease-free survival).

The study found no significant differences in recurrence rates or patterns between the two surgical methods, suggesting that RAMIE is a viable alternative to OTE for long-term outcomes in esophageal cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Robot-assisted minimally invasive thoracolaparoscopic esophagectomy versus open esophagectomy: long-term follow-up of a randomized clinical trial. de Groot, EM., van der Horst, S., Kingma, BF., et al.[2021]

In a study of 5170 patients with esophageal cancer, those who underwent robotic-assisted minimally invasive esophagectomy (RAMIE) had significantly better overall survival compared to those who had minimally invasive esophagectomy (MIE) or open esophagectomy (OE), with a median survival of 42 months.

Patients undergoing RAMIE had a lower risk of death, with hazard ratios indicating a 19% increased risk for MIE and a 22% increased risk for OE, suggesting that RAMIE may be a more effective surgical option for improving long-term outcomes in esophageal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term survival outcomes associated with robotic-assisted minimally invasive esophagectomy (RAMIE) for esophageal cancer. Byiringiro, I., Aurit, SJ., Nandipati, KC.[2023]

In a study using Wistar rats, the COX-2/PGE2 pathway was found to be significantly involved in the development of esophageal adenocarcinoma (EAC), with 90% of rats showing intestinal metaplasia and 40% progressing to cancer after inducing gastroduodenal reflux.

Selective inhibition of COX-2 and the EP2 receptor reduced cell proliferation in esophageal tissues, suggesting that targeting the EP2 receptor could be a promising strategy for preventing Barrett's associated adenocarcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of the prostaglandin E2 pathway in a rat model of esophageal adenocarcinoma. Piazuelo, E., Santander, S., Cebrián, C., et al.[2019]

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