Brief Summary

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.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

290

participants targeted

Target at P75+ for phase_2

Timeline

93mo left

Started Apr 2026

Longer than P75 for phase_2

Geographic Reach

1 country

2 active sites

Status

recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

7.7 years study duration

First Submitted

Initial submission to the registry

May 8, 2025

Completed

25 days until next milestone

First Posted

Study publicly available on registry

June 2, 2025

Completed

11 months until next milestone

Study Start

First participant enrolled

April 29, 2026

Completed

5.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2031

Expected

2.6 years until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2034

Last Updated

May 7, 2026

Status Verified

May 1, 2026

Enrollment Period

5.1 years

First QC Date

May 8, 2025

Last Update Submit

May 3, 2026

Conditions

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

Outcome Measures

Primary Outcomes (1)

progression free survival
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 (consisting of either progression in the number of metastases, recurrence at surgically treated metastasis, progression of ablated or irradiated metastasis, or recurrence of the primary tumor or regional lymph node metastasis) * Death due to any cause.
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

Secondary Outcomes (2)

Overall survival (OS)
Interval between randomization and death or last follow-up up to 53 months after study initiation
2. Quality of Life (QoL)
At 12 months after randomization.

Other Outcomes (2)

Levels of ctDNA circulating in plasma
before start of systemic treatment (t=0), at restaging (t=4 months) and during follow-up (at t= 8 months and t = 12 months)
Potential new (blood or tissue based) biomarkers that predict clinical outcome and response to treatment
before start of systemic treatment (t=0), at restaging (t=4 months) and during follow-up (at t= 8 months and t = 12 months)

Study Arms (2)

long duration of systemic therapy

EXPERIMENTAL

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.

Drug: ChemotherapyDrug: Targeted Systemic TherapyDrug: ImmunotherapyProcedure: SurgeryRadiation: Radiotherapy

Short duration of systemic therapy

ACTIVE COMPARATOR

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.

Drug: ChemotherapyDrug: Targeted Systemic TherapyDrug: ImmunotherapyProcedure: SurgeryRadiation: Radiotherapy

Interventions

ChemotherapyDRUG

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).