Organ-Preserving Endoscopic Resection & Adjuvant RADIO-immuno-chemotherapy for Esophageal Cancer — OPERARADIO  

Esophageal Cancer Clinical Trial

Official title: A Phase I Study of Organ-Preserving Endoscopic Resection & Adjuvant RADIO-immuno-chemotherapy for Esophageal Cancer (OPERA-RADIO)

Status Recruiting

Clinical Trial Summary

The goal of this study is to assess the safety of delivering concurrent adjuvant chemoradiation or immuno-radiation therapy after EMR/ESD in pT1b/T2N0 esophageal cancer patients. The main objectives of the study are:

1. Assess the feasibility of enrolling 10 patients.

2. Assess the safety of delivering concurrent adjuvant chemoradiation or immunoradiation therapy after EMR/ESD in pT1b/T2 esophageal cancer patients

Clinical Trial Description

This is a single center trial to assess feasibility and safety of conducting a multicenter Phase I non-randomized trial of adjuvant Durvalumab therapy in the treatment of pT1b/T2N0 esophageal cancer. The investigatory treatment, ARM1, will be endoscopic resection followed by adjuvant immunoradiation therapy. Patients that are recruited but are unable to receive immunotherapy will be recruited to ARM2 the current standard of care in chemoradiation therapy The study will include patients diagnosed with pT1b/T2 esophageal cancer after endoscopic resection that are ineligible for an esophagectomy or for those who decline an esophagectomy as treatment.

The current standard of care for treatment of pT1b/T2 esophageal cancer is esophagectomy with postoperative adjuvant chemotherapy. Depending on the detection of nodal metastasis during intraoperative nodal sampling, patients that are truly N0 can avoid postoperative adjuvant chemotherapy. Patients that are ineligible for esophagectomy or decline an esophagectomy as treatment are directed to concurrent chemoradiation (Table ESOPH-F, Adjani et al. 2019). Combined modality chemoradiation therapy, paclitaxel and carboplatin concurrent with radiation therapy (50 to 50.4 Gy) is classified as Category One treatment regime according to the most current CROSS protocol (van Hagen et al. 2012). Chemoradiation is the recommended first-line of preoperative treatment for patients that can tolerate an esophagectomy (ESOPH-F). It is also recommended as the first-line of concurrent treatment for localized esophageal cancers that are ineligible for esophagectomy (ESOPH-17). In the current standard of treatment, patients that are ineligible for esophagectomy or decline an esophagectomy and cannot tolerate chemoradiation are directed to radiation therapy as a palliative treatment. The goal of the current study is to provide a curative multi-modal option to patients that are ineligible for esophagectomy and to provide an alternative systemic therapy for patients that are not candidates for the current standard in multimodal treatments such as chemoradiation therapy. Patients may be considered ineligible for esophagectomy due to 1) inoperability of the tumour due to location, 2) the patient is considered high risk for serious intra-operative or post-operative complications and 3) patients may decline an esophagectomy as a line of treatment. Esophagectomy is a complicated surgical procedure associated with serious intraoperative and postoperative complications. Loss of organ function can result in life-long risk of complications. Endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) is currently routinely performed as a diagnostic and sampling procedure. The current study will determine the therapeutic and quality of life benefits of ESD/EMR in combination with systemic monotherapy and radiation therapies in a patient population that is ineligible for esophagectomy. The current study will assess feasibility of patient recruitment over an 18 month period and safety profile of Durvalumab as an adjuvant treatment within this patient population.

In patients with early-stage esophageal cancer with clinical T1 or T2N0 stage, clinical staging alone is unreliable. EMR/ESD is done both as a diagnostic and potentially curative procedure. EMR/ESD will identify if a patient truly has pT1 or pT2 disease. In patients with fully resected pT1a or low risk pT1b cancer (i.e., resected via EMR/ESD), adjuvant treatment is not indicated and would be considered to have greater risks than benefits. Thus, pursuing a neo-adjuvant therapy approach (i.e. giving immunoradiation therapy before EMR/ESD) should be avoided for the following reasons: 1) it would obscure the true pathologic stage of the cancer 2) it would make the EMR/ESD more complicated due to submucosal fibrosis and would thus increase the risks of complications 3) it would put people through treatments they would never have needed and would only confer risks rather than benefits (i.e. patients with fully resected pT1a or low-risk pT1b cancer). ;

Related Conditions & MeSH terms

• Esophageal Cancer
• Esophageal Neoplasms

• NCT number: NCT05667298
• Study type: Interventional
• Source: University of Manitoba
• Contact: Biniam Kidane, MD
• Phone: 204-787-5625
• Email: bkidane@hsc.mb.ca
• Status: Recruiting
• Phase: Phase 1
• Start date: March 1, 2023
• Completion date: June 1, 2026