Neoplasms

Digestive System Diseases

All Conditions

Rare Diseases

Esophageal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Esophageal Cancer

All Drugs and Chemicals

Antineoplastic Agents

Immunomodulating Agents

Durvalumab

Immunologic Factors

The primary/preferred adjuvant therapy will be immunoradiotherapy (ARM1); however, if this combination is felt to be too high-risk for specific patients, the next preferred therapy will be immunotherapy without radiation (ARM1B).

Some patients have medical conditions, i.e., severe auto-immune disease that prohibits them from receiving immunotherapy. In such patients, adjuvant therapy will be provided in the form of concurrent chemoradiotherapy (ARM2).

Durvalumab treatment is to begin six weeks following patient ESD/EMR surgery.

Patients may delay dosing under the following certain circumstances:

1. Dosing may be delayed per Toxicity Management Guidelines (Appendix IV), due to either an immune or a non-immune-related AE.
2. Dosing intervals of subsequent cycles may be shortened as clinically feasible in order to gradually align treatment cycles with the schedule of tumor efficacy (RECIST) and PRO assessments. Subsequent time between 2 consecutive doses cannot be less than 22 days, based on the half-lives of durvalumab (see current Investigator Brochure for durvalumab).
3. Standard of Care Arm (CROSS):
4. Patients may delay and subsequently resume dosing per local standard clinical practice.

If dosing must be delayed for reasons other than treatment-related toxicity, dosing will occur as soon as feasible.

Adjuvant Immunoradiotherapy (ARM1) and Adjuvant Immunotherapy (ARM1B)

Adjuvant chemoradiotherapy

Biniam Kidane, MD

Jennifer Basa

Carla Dizon

Biniam Kidane

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

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).

The primary/preferred adjuvant therapy will be immunoradiotherapy (ARM1); however, if this combination is felt to be too high-risk for specific patients, the next preferred therapy will be immunotherapy without radiation (ARM1B). Some patients have medical conditions, i.e., severe auto-immune disease that prohibits them from receiving immunotherapy. In such patients, adjuvant therapy will be provided in the form of concurrent chemoradiotherapy (ARM2).

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

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

Assess the feasibility of enrolling 10 patients (i.e. Raw count of number of patients enrolled in 1.5 years)

Assess the safety of delivering concurrent adjuvant chemoradiation or immunoradiation therapy after EMR/ESD in pT1b/T2 esophageal cancer patients. This will be done using CTCAE. This will be descriptive and be based on proportion of patients developing Grade 3 or above adverse events.

Determine health-related quality of life, based on longitudinal assessment of validated FACT-E scale (Functional Assessment of Cancer Therapy - Esophageal). This will be descriptive and be based on the change from pretreatment/baseline score to the score at the 2-year mark post-resection. FACT-E has 44 questions scored on a 5-point Likert scale, with lower scoring indicating less effects on quality of life.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Organ-Preserving Endoscopic Resection & Adjuvant RADIO-immuno-chemotherapy for Esophageal Cancer	NCT05667298	Esophageal Canc...	Adjuvant Immuno... Adjuvant chemor...	18 Years -	University of Manitoba
Organ-Preserving Endoscopic Resection & Adjuvant RADIO-immuno-chemotherapy for Esophageal Cancer	NCT05667298	Esophageal Canc...	Adjuvant Immuno... Adjuvant chemor...	18 Years -	University of Manitoba

Spots Global Cancer Trial Database for adjuvant immunoradiotherapy (arm1) and adjuvant immunotherapy (arm1b)