Chemoimmunotherapy Followed by Surgery for Oligometastatic Esophagogastric Cancer: (TORO Protocol) (TORO)
Chemoimmunotherapy Followed by Surgery for Oligometastatic Esophageal and Gastric Cancer: A Phase II Clinical Trial (TORO Protocol)
Study Overview
Status
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.
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Frances Allison
- Phone Number: 437-233-4303
- Email: Frances.Allison@uhn.ca
Study Locations
-
-
Ontario
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Toronto, Ontario, Canada, M5G 2C4
- Recruiting
- Toronto General Hospital, University Health Network
-
Contact:
- Frances Allison
- Phone Number: 437-233-4303
- Email: Frances.Allison@uhn.ca
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
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:
- Patients with overt peritoneal or pleural dissemination, as detected on PET-CT or regular CT-scan. In patients in whom a diagnostic laparoscopy is indicated (to assess gastric involvement and the possibility to perform gastric tube reconstruction or to exclude peritoneal disease), tumor-positive cytology peritoneal fluid is also an exclusion criteria. Of note, positive microscopic peritoneal cytology which converts to negative after treatment is not an exclusion criteria (i.e. peritoneal or pleural fluid cytology must be negative at the time of enrollment, with no gross disease identified initially).
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Other: Surgical Arm
Surgical resection followed by preoperative chemoimmunotherapy for oligometastatic esophagogastric cancer
|
Surgical resection followed by preoperative chemoimmunotherapy for oligometastatic esophagogastric cancer
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Overall survival
Time Frame: 5 years
|
Overall survival outcomes for patients undergoing systemic treatment, primarily with chemoimmunotherapy, followed by surgery in patients with oligometastatic esophageal and GEJ cancer
|
5 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Surgical safety
Time Frame: Within first 30 days after surgery
|
Review of surgical safety, defined by surgical complications
|
Within first 30 days after surgery
|
|
Mortality
Time Frame: Within first 30 days after surgery
|
Review of surgical safety, defined by mortality within the first 30 days
|
Within first 30 days after surgery
|
|
Progression free survival
Time Frame: 2 years and 5 years
|
Review of distant and loco-regional recurrence
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2 years and 5 years
|
|
Quality of Life questionnaires
Time Frame: Pre-treatment, post-chemoimmunotherapy/pre-op, post op visit @ 30 days, 6 months, 1 year, 18 months and 2 and 5 years
|
Use of FACT E questionnaires at different timepoints to assess patient reported outcomes
|
Pre-treatment, post-chemoimmunotherapy/pre-op, post op visit @ 30 days, 6 months, 1 year, 18 months and 2 and 5 years
|
Collaborators and Investigators
Investigators
- Principal Investigator: Dr. Elliot Wakeam, Toronto General Hospital-UHN
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CTO Project 4717
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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