Best time for minimally invasive local treatment after first-line systemic therapy for limited (oligo) esophageal or stomach cancer
Timing of Minimally Invasive Local Treatment After First-Line Systemic Therapy in Oligometastatic Esophageal or Gastric Adenocarcinoma: A Randomized Prospective Clinical Study (OMEC-5)
This trial will test whether giving local treatment (surgery or radiation) earlier or later after first-line systemic therapy works better for people whose esophageal or stomach cancer has spread to only a few sites.
Quick facts
| Phase | Phase2; Phase3 |
|---|---|
| Study type | Interventional |
| Enrollment | 290 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) Academic / other |
| Drugs / interventions | trastuzumab, zolbetuximab, immunotherapy, prednisone, nivolumab, pembrolizumab, chemotherapy, radiation |
| Locations | 2 sites (Amsterdam and 1 other locations) |
| Trial ID | NCT07000253 on ClinicalTrials.gov |
What this trial studies
Patients with oligometastatic esophageal or gastric adenocarcinoma receive standard first-line systemic therapy including chemotherapy, targeted agents and/or immunotherapy, then are assigned to shorter versus longer systemic therapy duration before minimally invasive local treatment to primary and metastatic sites. The trial enrolls about 414 patients across multiple European centers led by Amsterdam UMC and UMC Utrecht and follows participants for disease control and related outcomes for about 18 months after enrollment completes. Local treatment options include surgery or radiotherapy when the multidisciplinary team considers radical local therapy feasible. The study also collects tissue and blood samples to search for biomarkers that predict who benefits from this timing strategy.
Who should consider this trial
Good fit: Adults (≥18) with histologically confirmed esophageal, gastric, or gastroesophageal junction adenocarcinoma who have OMEC-consensus oligometastatic disease, a resectable primary and metastases deemed amenable to radical local treatment, WHO performance status 0–2, and an indication for checkpoint inhibition or targeted therapy (e.g., PD-L1 CPS ≥1).
Not a fit: Patients with widespread metastatic disease beyond OMEC-defined oligometastases, unresectable primary or metastatic sites, poor performance status, or no indication for the systemic therapies used in the protocol are unlikely to benefit from this timing approach.
Why it matters
Potential benefit: If successful, this could help doctors choose the best timing for local treatment to improve disease control and potentially extend survival for patients with oligometastatic esophageal or gastric cancer.
How similar studies have performed: Prior retrospective and smaller prospective studies have suggested adding local treatment after systemic therapy can extend survival in oligometastatic esophagogastric cancer, but high-quality data on optimal timing are limited.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Age ≥18 years * Ability to provide written informed consent * Histologically confirmed esophageal, gastric or gastroesophageal junction tumor with oligometastatic (M1) disease defined according to the OMEC consensus statement: * One organ with ≤3 metastases or 1 involved extra-regional lymph node station (based on the TNM 8 classification) * ≤3 unilobar liver metastases or ≤2 bilobar liver metastases * ≤ 3 unilateral lung metastases * Unilateral adrenal gland involvement * Metastasis confined to 1 bone structure or 1 soft tissue compartment * Synchronous oligometastatic disease with a resectable primary tumor or metachronous oligometastatic disease (in the event of a locoregional recurrence this should be resectable) * Metastases should be deemed amenable by the international multidisciplinary expert team for radical local treatment * WHO performance status 0-2 * Indication for checkpoint inhibition and/or targeted therapy * PD-L1 with a CPS of 1 or higher as per local clinical practice for immunotherapy use * HER2 overexpression as per local clinical practice for trastuzumab use * Claudin 18.2 overexpression as per local clinical practice for zolbetuximab use. * Any other biomarker that allows targeted therapy in first line approved by EMA * No prior systemic therapy for metastatic disease * CT-scan ≤8 weeks prior to inclusion * Ability to undergo local treatment and start systemic treatment beyond 18 weeks of total systemic treatment. Exclusion Criteria: * Squamous cell carcinoma * Brain metastases * Peritoneal or pleural carcinomatosis * Patients with MSI dMMR * Uncontrolled immunodeficiency (e.g. AIDS) * Peripheral neuropathy \>CTCAE grade 1, precluding start of full dose oxaliplatin treatment * Both organ metastasis and extra-regional lymph node metastasis * Conditions precluding local treatment or systemic therapy for oligometastatic disease: * Serious medical comorbidities precluding local treatment (e.g., interstitial lung disease in patients with pulmonary metastasis) * Clinical or radiological evidence of spinal cord compression or epidural tumor within 2 mm of the spinal cord * Simultaneous other malignancy or previous other malignancy with a disease-free period of \<5 years, except adequately treated non-melanoma skin cancer or in-situ cancers * Uncontrolled (bacterial) infections * Significant concomitant diseases preventing the safe administration of study drugs or likely to interfere with study assessments * Uncontrolled angina pectoris, cardiac failure or clinically significant arrhythmias * Continuous use of immunosuppressive agents equivalent to \>10 mg daily prednisone * Concurrent use of the antiviral agent sorivudine or chemically related analogues, such as brivudine * Pregnancy or breast feeding * Patients (M/F) with reproductive potential not implementing adequate contraceptive measures
Where this trial is running
Amsterdam and 1 other locations
- Amsterdam University Medical Center — Amsterdam, Netherlands (Recruiting)
- UMC Utrecht — Utrecht, Netherlands (Not_yet_recruiting)
Study contacts
- Principal investigator: Peter van Rossum, MD, PhD — Amsterdam UMC
- Study coordinator: Hanneke van Laarhoven, MD, PhD, PhD
- Email: h.vanlaarhoven@amsterdamumc.nl
- Phone: +31204444321
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.