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

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.

Conditions

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

Interventions

DRUG

Chemotherapy

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).

DRUG

Targeted Systemic Therapy

Biomarker selected patients will receive trastuzumab, zolbetuximab or any other targeted agent according to standard of care.

DRUG

Immunotherapy

Biomarker selected patients will recieve checkpoint inhibitors according to standard care

PROCEDURE

Surgery

If the primary tumor is present, this tumor will be surgically removed. Metastases may also be removed by surgery.

RADIATION

Radiotherapy

Metastases may be irradiated

Sponsors & Collaborators

• UMC Utrecht

  collaborator OTHER

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

  lead OTHER

Principal Investigators

• Peter van Rossum, MD, PhD · Amsterdam UMC

• Richard van Hillgersberg, MD, PhD · UMC Utrecht

• Hanneke van Laarhoven, MD, PhD, PhD · Amsterdam UMC

• Tiuri Kroese, MD, PhD · University of Zurich

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-04-29

Primary Completion

2031-06-30

Completion

2034-01-31

Countries

• Netherlands

Study Locations