First Line gastroeSOphageal metastatiC canceR primAry and disTant (if Oligometastatic) lEsions-directed Radiotherapy, a Multicentric, Phase III, Randomized Controlled Trial (SOCRATE)

The aim of the study is to evaluate the efficacy of radiotherapy on the primary site of gastroesophageal cancer and extracranial stereotactic radiotherapy on metastases before the use of standard systemic therapy, in cases of limited disease burden (in the experimental group), compared to the standard group, which does not receive radiotherapy. This prospective, multicenter, randomized trial aims to evaluate the efficacy of the unconventional approach versus the conventional one in increasing the percentage of asymptomatic patients due to the direct effect of the primary tumor or metastases. "Randomized" means that the assignment to one of the treatment groups mentioned above will be random, not influenced by the physician or the patient's condition. Therefore, your participation in either of the two treatments under study will be assigned randomly and not predetermined. This randomness is crucial for a proper analysis of the results at the end of the study, which will help clarify whether there are differences between the two proposed treatments. This also means that you may not receive direct benefits from participating in this study, as it is a research study.

Study Overview

• Status: Active, not recruiting
• Conditions: Gastroesophageal Cancer (GC)
• Intervention / Treatment: Drug: Standard systemic therapy (chemotherapy); Radiation: Radiation Therapy + standard sistemic therapy (chemoteraphy)

• Study Type: Interventional
• Enrollment (Estimated): 108
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • RM
    • Rome, RM, Italy, 00168
      • Policlinico Universitario Agostino Gemelli IRCSS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients diagnosed with gastroesophageal cancer (i.e.: esophagus, gastroesophageal junction, stomach), for both major squamous cell (SCC) and adenocarcinomatous (ADK) histologies, metastatic, candidate for first-line standard systemic treatment; either newly diagnosed in metastatic stage or first progression to metastasis.
• Obtaining informed consent.
• Patients >18 years of age
• ECOG 0-2
• Performance of imaging (CT with mdc, MRI with mdc, CT-PET with appropriate tracer) adequate for baseline local and systemic staging and likely to be similarly repeatable at 6 and 12 months after randomization
• Confirmation at the time of randomization, by the Radiation Therapy Center, that all potentially planned treatments can be performed for the patient (if enrolled in experimental arm) within a maximum of 25 days total before referral to the Medical Oncology Center for systemic therapy

Exclusion Criteria:

• Metastatic picture of line following the first
• Technical or organizational inability to the eventual deadline for radiation treatments within 25 days of randomization
• Inability to express independent consent to treatments
• Pregnancy
• Patient in hospice or with prognosis < 6 months
• Predicted unavailability for follow-up at 6 months
• Absence of adequate or likely non-repeatable pretreatment imaging study at 6 and 12 months
• Previous radiation therapy
• Previous radiometabolic therapy
• Inability to maintain treatment position for SBRT
• Symptomatic emergent or other presentation precluding study development as planned (e.g., epidural compression of the spinal cord or cauda equina)
• Previous chemotherapy, immunotherapy or target therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Standard systemic therapy without RT/SBRT combination; The patients will go to standard therapy (chemotherapy treatment with carboplatin-taxol or with drugs that the oncologist that the oncologist considers most useful.) without RT/SBRT combination	Drug: Standard systemic therapy (chemotherapy); The patients will go to standard therapy (chemotherapy treatment with carboplatin-taxol or with drugs that the oncologist that the oncologist considers most useful.) without RT/SBRT combination; Other Names: standard; sistemic therapy; No radiation
Experimental: Standard systemic therapy with RT/SBRT combination; Standard systemic therapy (chemotherapy treatment with carboplatin-taxol or with drugs that the oncologist considers most useful) + combination of RT on the primary gastroesophageal Gross Tumor Volume (GTV) + SBRT on each of the distal lesions for oligometastatic or limited metastatic spread patients (to be delivered prior to initiation of systemic therapy).	Radiation: Radiation Therapy + standard sistemic therapy (chemoteraphy); Standard systemic therapy (chemotherapy treatment with carboplatin-taxol or with drugs that the oncologist considers most useful) + combination of RT on the primary gastroesophageal Gross Tumor Volume (GTV) + SBRT on each of the distal lesions for oligometastatic or limited metastatic spread patients (to be delivered prior to initiation of systemic therapy).; Other Names: SBRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disappearance of symptoms	Percentage difference in the rate of patients with symptom (from primary tumor or metastasis) developed within the first 6 months.	From the week after the treatment up to 12 months after

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain level	Level of metastasis-associated or primary pain (presence/absence, level and response) at 6 months	From the week after the treatment up to 12 months after
Radiotherapy use	Rate of recourse to Radiotherapy for pain, obstruction, bleeding or other symptom referable to the primary at 6 months from randomization (and not present at randomization)	From the week after the treatment up to 12 months after

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2024
• Primary Completion (Estimated): October 30, 2029
• Study Completion (Estimated): November 30, 2029

Study Registration Dates

• First Submitted: March 26, 2025
• First Submitted That Met QC Criteria: April 3, 2025
• First Posted (Actual): April 10, 2025

Study Record Updates

• Last Update Posted (Actual): May 11, 2025
• Last Update Submitted That Met QC Criteria: May 7, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Gastroesophageal cancer; metastatic gastroesophageal cancer
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis
• Other Study ID Numbers: 0001634/24

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No