Timing of Minimally Invasive Local Treatment After First-Line Systemic Therapy in Oligometastatic Esophageal or Gastric Adenocarcinoma

Sponsor
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Study ID
NCT07000253
Phase
PHASE2/PHASE3
Status
Recruiting
Apply to this trial

Conditions

  • Esophageal Cancer
  • Esophageal Carcinoma
  • Gastric (Cardia, Body) Cancer
  • Gastric (Stomach) Cancer
  • Gastric Adenocarcinoma
  • Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma or Esophageal Carcinoma

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Chemotherapy — DRUG
    Chemotherapy preferably CapOx (capecitabine + oxaliplatin) or FOLFOX (5-fluoruracil, leucovorin and oxaliplatin) will be combined with immunotherapy (preferably nivolumab or pembrolizumab) and/or targeted therapy (for example trastuzumab in the case of HER2 overexpression or zolbetuximab in the case of Claudin 18.2 overexpression). These regiments are the standard-of-care (SOC) combination therapies used in this study. Acceptable chemotherapy regimens predominantly for Asian centers include SOX (S-1 and Oxaliplatin).
  • Targeted Systemic Therapy — DRUG
    Biomarker selected patients will receive trastuzumab, zolbetuximab or any other targeted agent according to standard of care.
  • Immunotherapy — DRUG
    Biomarker selected patients will recieve checkpoint inhibitors according to standard care
  • Surgery — PROCEDURE
    If the primary tumor is present, this tumor will be surgically removed. Metastases may also be removed by surgery.
  • Radiotherapy — RADIATION
    Metastases may be irradiated

Study Details

Purpose of the Study: This clinical study investigates whether a shorter or longer duration of systemic therapy before local treatment (surgery or radiation) results in better disease control in patients with esophageal or gastric cancer with a limited number of metastases, also known as oligometastases. Background: In about 25% of patients with advanced esophageal or gastric cancer, the disease spreads to only a few sites (oligometastatic disease). Prior studies suggest that local treatment after systemic therapy may extend survival in this subgroup. However, it is unclear how long systemic therapy should last before initiating local treatment. The OMEC-5 study aims to clarify this and identify potential biomarkers for treatment response. Study Design: Initiated by Amsterdam UMC and UMCU and conducted in multiple hospitals across Europe. Total of 414 patients to be enrolled. Duration: \~53 months (35 months enrollment + 18 months follow-up). Approved by the medical ethics committee at Amsterdam UMC. Procedure: Eligibility screening: Includes physical exam, blood tests (incl. circulating tumor cells), medical history review, and confirmation of oligometastases by an expert panel. Initial treatment: All participants receive 4 months of standard systemic therapy (chemotherapy + immunotherapy and/or targeted therapy depending on tumor markers like HER2 or Claudin 18.2). Response assessment (Review 1): Imaging and/or laparoscopic examination. If oligometastases persist and tumors have not progressed, participants are randomized into two groups: Group A (longer systemic therapy): 4 more months of systemic therapy, then local treatment if disease is stable, followed by 4 months of immunotherapy ± targeted therapy. Group B (shorter systemic therapy): Immediate local treatment followed by 4 months of systemic therapy, then reassessment and potentially 4 months of immunotherapy ± targeted therapy. Follow-up: Regular scans and quality-of-life questionnaires (5 times), and periodic blood sampling (4 times). Treatments Involved: Chemotherapy: CapOx or FOLFOX Immunotherapy: nivolumab or pembrolizumab Targeted therapy: trastuzumab (HER2-positive) or zolbetuximab (Claudin 18.2-positive) Potential Benefits and Risks: Patients may benefit from better disease control and a personalized treatment strategy. Known side effects relate to the standard treatments used (chemo, immuno, targeted therapies), and no extra medical risk is expected beyond routine care. Possible inconveniences include blood draws, scans, minor surgery (laparoscopy), and time investment. Data and Sample Handling: Personal data and tumor/blood samples are coded and securely stored. Data may be used for future cancer research if the patient consents. Participants can withdraw at any time. Confidentiality and Privacy: Patient data are kept confidential, and participants have rights to access or delete their data. Privacy measures comply with GDPR and Dutch law. Compensation and Insurance: Participation is voluntary, with no financial compensation. Standard treatment costs are covered by healthcare insurance. No extra insurance is required, as the treatment aligns with standard care practices.

Key Dates

Start date
Apr 29, 2026
Status verified
May 2026
Primary completion
Jun 30, 2031
Completion
Jan 31, 2034

Study Design

Enrollment
290 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: long duration of systemic therapy
    Patients with no disease progression at 4 months (18 weeks) after systemic therapy with oxaliplatin, fluorpyrimidine, checkpoint inhibitor and/or taregted therapy and fit for local treatment will receive 4 additional months of systemic therapy and subsequent evaluation for local treatment to all disease sites.
  • Active Comparator: Short duration of systemic therapy
    Patients with no disease progression at 4 months (18 weeks) after systemic therapy oxaliplatin, fluorpyrimidine, checkpoint inhibitor and/or targeted therapy and fit for local treatment will recieve direct local treatment to all disease sites.

Primary Outcome Measure

progression free survival [ Time Frame: the time interval from the date of randomization to the date of first occurrence of the following events (or last follow-up) up to 53 months after study initiation: Disease progression, death ]

Central Contacts

Related Studies