h-APC Margin Ablation for Colon Polyps

(h-APC_EMR Trial)

Overseen By Julie Fleury

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)

Disqualifiers: Invasive carcinoma, Inflammatory bowel disease, Poor health, others

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

Compensation: Varies

Number of Visits: 4

Duration: 1 day

376 Participants Needed

Trial Summary

What is the purpose of this trial?

Endoscopic Mucosal Resection (EMR) is the current standard for effective endoscopic resection of such colon adenomas. If resection is possible in one piece (so-called "en bloc" resection) then recurrence rates are low. However, most non-pedunculated polyps \>2 cm are removed in pieces ("piece-meal" resection) which leads to disease recurrence rates between 12-30%. In the March 2019 issue of Gastroenterology Bourke et al. presented that post-EMR ablation of the resection margins using soft coagulation with the tip of a resection snare reduces adenoma recurrence to 5% compared to 21% recurrence found in the control group. Hybrid Argon Plasma Coagulation (h-APC) combines an ablation technique (APC) with the option for submucosal saline injection using a high-pressure water jet. The technique allows to lift of dysplastic epithelium thus creating a safety cushion under the mucosa is lifted with a saline injection and then to ablate larger areas more thoroughly and with a higher energy setting, with a low risk for side effects or complications. The study hypothesis is that routine use of hybrid Argon Plasma Coagulation (h-APC) for ablation of the post-EMR resection margins and resection surface area will reduce post-EMR adenoma recurrence to 5% or lower.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have a coagulopathy (a condition affecting blood clotting) with an elevated INR (a measure of blood clotting) or low platelets, you may not be eligible to participate.

What data supports the effectiveness of the treatment h-APC Margin Ablation for Colon Polyps?

Research shows that using hybrid argon plasma coagulation (h-APC) after endoscopic mucosal resection (EMR) can help reduce the recurrence of large colon polyps. Studies have found that this combination treatment results in low rates of polyp recurrence, suggesting it is effective in preventing polyps from coming back. ^{1 2 3 4 5}

Is the h-APC Margin Ablation for Colon Polyps safe?

Research indicates that hybrid argon plasma coagulation (h-APC) used with endoscopic mucosal resection (EMR) is generally considered safe for treating large colon polyps, with studies showing it may reduce recurrence rates. Additionally, argon plasma coagulation (APC) has been used safely for other conditions like early gastric and esophageal cancers, suggesting its general safety in humans. ^{1 2 3 5 6}

What makes the h-APC Margin Ablation treatment for colon polyps unique?

The h-APC Margin Ablation treatment is unique because it combines endoscopic mucosal resection (EMR) with hybrid argon plasma coagulation (h-APC), which involves using a gas to create a controlled burn to remove polyps and prevent their recurrence. This combination allows for precise removal of polyps with minimal damage to surrounding tissues, which is different from traditional methods that may not offer the same level of precision and safety. ^{7 8 9 10 11}

Research Team

Daniel von Renteln, MD, PhD

Principal Investigator

Centre hospitalier de l'Université de Montréal (CHUM)

Eligibility Criteria

This trial is for patients needing removal of large, non-pedunculated colorectal polyps (≥20 mm) and who can provide consent. It's open to all ethnicities and races but excludes those with invasive carcinoma in the study polyp, prior partial EMR, certain lesion types, severe health issues (ASA class>3), pregnant or breastfeeding individuals, inflammatory bowel disease sufferers, emergency cases, coagulopathy or poor bowel preparation.

Inclusion Criteria

People of all ethnicities and races are eligible to participate.

Written informed consent

I am referred for a procedure to remove large non-pedunculated polyps in my colon.

Exclusion Criteria

Pedunculated polyps (as defined by Paris Classification type Ip or Isp)

Poor bowel preparation (Boston bowel prep score ≤2)

I am undergoing an emergency colonoscopy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Treatment

Endoscopic Mucosal Resection (EMR) combined with hybrid Argon Plasma Coagulation (h-APC) for ablation of the resection margins

1 day

1 visit (in-person)

Follow-up 1

Colonoscopy to assess recurrence and perform additional h-APC treatment if necessary

4 months (± 2 months)

1 visit (in-person)

Follow-up 2

Additional colonoscopy for patients with recurrence to assess eradication rates

4 months (± 2 months) after Follow-up 1

1 visit (in-person)

Long-term Follow-up

Monitoring for complete adenoma eradication and complications within 1 year after the initial EMR

1 year

Treatment Details

Interventions

• EMR procedure
• Hybrid Argon Plasma Coagulation

Trial Overview The trial tests Hybrid Argon Plasma Coagulation (h-APC) after Endoscopic Mucosal Resection (EMR) for colon adenomas. h-APC aims to reduce recurrence by lifting the mucosa with saline injection before ablation. This follows evidence that margin ablation post-EMR significantly lowers adenoma recurrence rates.

Participant Groups

Group I: Group treatment h-APC and EMR Experimental Treatment 1 Intervention

Standard endoscopic mucosal resection (EMR) technique will be used for primary removal of all polyps. Submucosal injection will be used to lift the polyp from the muscularis propria. Injection is used as per the current standard of care using a contrast agent and a lifting agent (e.g. NaCl 0.9% or Voluven). Snare electrocautery resection will be facilitated until complete visible removal of the complete polyp. Electrocautery snare technique is facilitated using standard microprocessor controlled electrocautery (e.g. ERBE VIO Endocut 3-1-6). Ablation of the margin after visibly complete removal of the polyp is routinely applied. For thermal ablation hybrid APC (Erbe Hybrid APC) will be applied using standard settings on the margin and resection base. Once resection and thermal ablation is considered complete the mucosal defect can be closed with clips or another preventative measure applied to reduce the risk for post-polypectomy bleeding.

EMR procedure is already approved in European Union, United States for the following indications:

Approved in European Union as EMR procedure for:

• Colorectal polyps
• Adenomas
• Sessile serrated lesions
• Adenocarcinomas

Approved in United States as EMR procedure for:

• Colorectal polyps
• Adenomas
• Sessile serrated lesions
• Adenocarcinomas

Who Is Running the Clinical Trial?

Centre hospitalier de l'Université de Montréal (CHUM)

Lead Sponsor

Trials

389

Recruited

143,000+

Dr John levenick

Collaborator

Trials

1

Recruited

380+

Dr Alessandro Repici

Collaborator

Trials

1

Recruited

380+

Penn State University

Collaborator

Trials

380

Recruited

131,000+

University of Milan

Collaborator

Trials

268

Recruited

307,000+

Erbe Elektromedizin GmbH

Industry Sponsor

Trials

14

Recruited

840+

University of British Columbia

Collaborator

Trials

1,506

Recruited

2,528,000+

Unity Health Toronto

Collaborator

Trials

572

Recruited

470,000+

Findings from Research

In a study of 23 elderly patients (average age 77.5 years) with early gastric cancer, argon plasma coagulation (APC) was found to be a safe and effective treatment option, especially for those who could not undergo surgery or had unsuccessful EMR.

After a median follow-up of 42 months, 15 patients showed no recurrence of cancer, and APC was successfully used to manage recurrences without serious complications, highlighting its potential as a viable alternative treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Argon plasma coagulation for the treatment of early gastric cancer. Murakami, M., Nishino, K., Inoue, A., et al.[2013]

In a study of 246 patients with large colonic polyps (≥20 mm), the use of argon plasma coagulation (APC) on the EMR edge significantly reduced local adenoma recurrence rates after endoscopic mucosal resection (EMR).

Only 5% of patients had residual tumors at the resection site, suggesting that APC may enhance the effectiveness of EMR in preventing recurrence, although further validation in randomized controlled trials is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cap-fitted endoscopic mucosal resection of ≥ 20 mm colon flat lesions followed by argon plasma coagulation results in a low adenoma recurrence rate. Raju, GS., Lum, P., Abu-Sbeih, H., et al.[2020]

In a study involving 101 colorectal polyps from 84 patients, the use of hybrid argon plasma coagulation (h-APC) after endoscopic mucosal resection (EMR) resulted in a very low recurrence rate of only 2.2% during follow-up colonoscopies.

The procedure demonstrated a high technical success rate with minimal serious adverse events, indicating that EMR with h-APC is a safe and effective method for managing large colorectal polyps.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EMR combined with hybrid argon plasma coagulation to prevent recurrence of large nonpedunculated colorectal polyps (with videos). Motchum, L., Levenick, JM., Djinbachian, R., et al.[2022]

In a study of 22 patients, argon-plasma coagulation (APC) achieved a high complete ablation rate of 90.9% for flat colorectal adenomas, demonstrating its efficacy as a treatment method.

The procedure was found to be safe, with no major complications reported, although a recurrence rate of 20% was noted, primarily in the rectum, indicating the need for further research to confirm these results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of argon plasma coagulator ablation therapy for flat colorectal adenomas. García, A., Núñez, O., González-Asanza, C., et al.[2019]

In a pilot study involving 40 patients, the novel hybrid argon plasma coagulation-assisted EMR (hAPC-EMR) technique showed a 0% local recurrence rate of large, sessile colon polyps after 6 months, indicating high efficacy.

The safety profile of hAPC-EMR was favorable, with only 7.5% of patients experiencing post-polypectomy bleeding and no cases of post-polypectomy syndrome reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hybrid argon plasma coagulation-assisted endoscopic mucosal resection for large sessile colon polyps to reduce local recurrence: a prospective pilot study. Motz, VL., Lester, C., Moyer, MT., et al.[2023]

Argon plasma coagulation (APC) is a safe and effective alternative treatment for superficial esophageal cancer in patients who cannot undergo endoscopic mucosal resection (EMR), with no incidents of bleeding or infection reported in a study of 10 patients.

While APC is easier to perform and has a lower risk of complications compared to EMR, it is less effective in achieving complete resection of cancerous lesions, making it suitable only for specific cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Argon plasma coagulation for the treatment of superficial esophageal carcinoma. Nomura, T., Miyashita, M., Makino, H., et al.[2019]

Carbon ion radiotherapy (RT) demonstrated high efficacy in treating chordomas and low-grade chondrosarcomas, achieving 100% local control for chondrosarcomas and 87% for chordomas at a 3-year follow-up with a median follow-up of 15 months.

The treatment was safe, with no severe side effects observed, and indicated potential for higher biological effectiveness of carbon ions, as evidenced by partial tumor remission in 31% of chordoma patients and 17% of chondrosarcoma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carbon ion radiotherapy for chordomas and low-grade chondrosarcomas of the skull base. Results in 67 patients. Schulz-Ertner, D., Nikoghosyan, A., Thilmann, C., et al.[2019]

Carbon ion therapy offers precise targeting of tumors through the spread out Bragg peak, which maximizes energy delivery to the tumor while minimizing damage to surrounding healthy tissues.

This therapy is particularly effective against radioresistant tumors, making it a preferred option for treating non-resectable tumors that pose a local threat, as it has a higher biological efficiency compared to traditional X-rays or protons.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Particle therapy: carbon ions]. Pommier, P., Hu, Y., Baron, MH., et al.[2018]

Carbon-ion radiotherapy (C-ion RT) demonstrated long-term efficacy for treating oral mucosal malignant melanoma (OMM), with 5-year local control, overall survival, and progression-free survival rates of 89.5%, 57.4%, and 51.6%, respectively, based on a study of 19 patients followed for a median of 61 months.

While C-ion RT showed effectiveness, it also had some associated risks, including grade 2 and 3 osteoradionecrosis in a number of patients, particularly those with teeth in the treatment area, highlighting the need for careful planning in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcomes after carbon-ion radiotherapy for oral mucosal malignant melanoma. Naganawa, K., Koto, M., Takagi, R., et al.[2020]

Carbon ion radiotherapy (C-ion RT) demonstrated a high 5-year local control rate of 92% in treating locally advanced adenoid cystic carcinoma (ACC) of the tongue base, indicating its efficacy for this challenging cancer type.

While C-ion RT was effective, it did have some safety concerns, with 2 patients experiencing severe mandible osteoradionecrosis and 1 patient suffering from significant hemorrhage, highlighting the need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the safety and efficacy of carbon ion radiotherapy for locally advanced adenoid cystic carcinoma of the tongue base. Koto, M., Hasegawa, A., Takagi, R., et al.[2018]

In a study of 11 patients with locally advanced hepatocellular carcinoma (HCC), carbon ion radiotherapy (C-ion RT) demonstrated a 3-year overall survival rate of 64% and a local control rate of 78%, indicating its effectiveness in managing this challenging condition.

C-ion RT was well-tolerated, with no patients experiencing severe toxicities or radiation-induced liver diseases, suggesting it is a safe treatment option for patients with LAHCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical impact of Hypofractionated carbon ion radiotherapy on locally advanced hepatocellular carcinoma. Shiba, S., Shibuya, K., Okamoto, M., et al.[2021]

References

1. Greece pubmed.ncbi.nlm.nih.gov

Argon plasma coagulation for the treatment of early gastric cancer. [2013]

2. Germany pubmed.ncbi.nlm.nih.gov

Cap-fitted endoscopic mucosal resection of ≥ 20 mm colon flat lesions followed by argon plasma coagulation results in a low adenoma recurrence rate. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

EMR combined with hybrid argon plasma coagulation to prevent recurrence of large nonpedunculated colorectal polyps (with videos). [2022]

4. Spain pubmed.ncbi.nlm.nih.gov

Safety and efficacy of argon plasma coagulator ablation therapy for flat colorectal adenomas. [2019]

5. Germany pubmed.ncbi.nlm.nih.gov

Hybrid argon plasma coagulation-assisted endoscopic mucosal resection for large sessile colon polyps to reduce local recurrence: a prospective pilot study. [2023]

6. Japan pubmed.ncbi.nlm.nih.gov

Argon plasma coagulation for the treatment of superficial esophageal carcinoma. [2019]

7. Germany pubmed.ncbi.nlm.nih.gov

Carbon ion radiotherapy for chordomas and low-grade chondrosarcomas of the skull base. Results in 67 patients. [2019]

8. France pubmed.ncbi.nlm.nih.gov

[Particle therapy: carbon ions]. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Long-term outcomes after carbon-ion radiotherapy for oral mucosal malignant melanoma. [2020]

10. United States pubmed.ncbi.nlm.nih.gov

Evaluation of the safety and efficacy of carbon ion radiotherapy for locally advanced adenoid cystic carcinoma of the tongue base. [2018]

11. England pubmed.ncbi.nlm.nih.gov

Clinical impact of Hypofractionated carbon ion radiotherapy on locally advanced hepatocellular carcinoma. [2021]