Chemoimmunotherapy Followed by Surgery for Oligometastatic Esophagogastric Cancer: (TORO Protocol)

NCT ID: NCT06668454

Last Updated: 2025-05-16

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-05-09
• Study Completion Date: 2035-05-09

Brief Summary

Esophageal cancer and cancers of the gastroesophageal junction (GEJ) are among the most common malignancies worldwide. The outcome for these patients remains very poor. Patients with limited spread of their cancer (oligometastatic disease) have a better prognosis than those with widespread disease. Recent advances in treatment therapies, including use of pre-operative immunotherapy, surgery and/or targeted radiation (SBRT) may help to prolong lifespan in patients with oligometastatic disease. Patients will undergo treatment for their oligometastatic esophageal or gastric cancer with pre-operative chemoimmunotherapy followed by surgery and possibly SBRT to evaluate the value of adding surgery and possibly SBRT to their treatment.

Detailed Description

Esophageal cancer and cancers of the gastroesophageal junction (GEJ) are among the most common malignancies worldwide, and the prognosis for patients with metastatic disease remain very poor. However, recent advances in systemic treatment modalities have shown promise for patients with oligometastatic disease, in particular with the incorporation of immunotherapy an targeted agents into systemic treatment regimens. The definition of oligometastatic disease varies across studies and primary sites, but it is generally agreed that patients with oligometastatic disease have a more favorable prognosis than those with widespread metastases. For patients with oligometastatic disease, which is variably defined as the presence of a limited number of metastases, the role of local treatment remains controversial. Chemoimmunotherapy followed by surgery has emerged as a potential treatment option for oligometastatic esophageal and gastric cancer, but further research is needed to evaluate its efficacy and safety and to provide prospective survival and recurrence information.

Several studies have investigated the use of surgery for oligometastatic esophageal cancer after chemo-immunotherapy. A retrospective study of 47 patients with oligometastatic esophageal cancer who underwent immunotherapy and surgery found that the median overall survival was 22 months, and the 2-year overall survival rate was 47.8%. A phase II study of chemoimmunotherapy followed by surgery for patients with oligometastatic esophageal cancer found that the 2-year progression-free survival rate was 60%, and the median overall survival had not been reached at the time of analysis. These studies suggest that surgery after immunotherapy may be associated with better survival outcomes for patients with oligometastatic esophageal cancer, but further research is needed to confirm these findings. SBRT has been evaluated previously in oligometastatic disease in a number of different settings, including in our own institution in studies that included esophageal cancer patients, although in very small numbers. These studies were encouraging but a more thorough evaluation in combination with surgical resection has not been completed.

Conditions

Esophageal Cancer; Gastric Cancer; Oligometastatic Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Surgical Arm

Surgical resection followed by preoperative chemoimmunotherapy for oligometastatic esophagogastric cancer

Group Type: OTHER

Surgical resection followed by preoperative chemoimmunotherapy for oligometastatic esophagogastric cancer

Intervention Type: PROCEDURE

Surgical resection followed by preoperative chemoimmunotherapy for oligometastatic esophagogastric cancer

Interventions

Surgical resection followed by preoperative chemoimmunotherapy for oligometastatic esophagogastric cancer

Surgical resection followed by preoperative chemoimmunotherapy for oligometastatic esophagogastric cancer

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Histologically-proven cT1-4aN0-3M1 adenocarcinoma or squamous cell carcinoma of the esophagus, or EGJ according to the 8th edition of the Union for International Cancer Control (UICC) TNM classification for Esophageal Cancer;
• Oligometastatic disease, which is defined as a maximum of five metastatic lesions, that is treatable by surgical resection or radiation. These five lesions can be present in a maximum of two organs (eg, liver, lung or adrenal gland). Lymph nodes are not counted as an organ. If metastatic retroperitoneal or supraclavicular lymph nodes are present, this lymph node site counts as one metastatic lesion, and together with the possible metastases in organs cannot exceed the number of five lesions.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1;
• Adequate cardiac and respiratory function by standard electrocardiogram and additional diagnostics in case of cardiopulmonary complaints or comorbidity (i.e. lung function test, or echocardiography)
• Adequate blood work parameters for systemic therapy as per treating medical oncologist in terms of ANC, platelet count and hemoglobin.
• Adequate renal function (glomerular filtration rate >50 mL/min or serum creatinine ≤1.5x upper level of normal (ULN)) and adequate liver function (total bilirubin < 2.5x ULN and alanine transaminase (ALT) < 3x ULN);
• A negative serum pregnancy test in women of child-bearing potential during screening period.
• Age >18 and <80 years old

Exclusion Criteria

• Multiple bone or brain metastases - up to one solitary bone met and/one solitary brain met is allowable as a metastatic site, if curative ablative radiotherapy can be given at the discretion of the treating physicians. Patients with multiple brain metastases or multiple bone metastases will be excluded.
• Any other condition that, in the opinion of the investigator, would make the patient unsuitable for the study; particularly any condition that would make the patient unfit for surgery, radiation, chemotherapy or a combination thereof.
• Active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs) except vitiligo or resolved childhood asthma/atopy. Replacement therapy, such as thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, is not considered a form of systemic treatment and is allowed. Use of non-systemic steroids is permitted.
• Patients with active pregnancy, or lactation.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Health Network, Toronto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dr. Elliot Wakeam

Role: PRINCIPAL_INVESTIGATOR

Toronto General Hospital-UHN

Locations

Toronto General Hospital, University Health Network

Toronto, Ontario, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Frances Allison

Role: CONTACT

Frances.Allison@uhn.ca

437-233-4303

Facility Contacts

Frances Allison

Role: primary

Frances.Allison@uhn.ca

437-233-4303

Other Identifiers

CTO Project 4717

Identifier Type: -

Identifier Source: org_study_id