MR-guided radiotherapy dose escalation for esophageal squamous cell carcinoma
Improving Outcome of Patients With Squamous Cell ESophageal CArcinoma by Dose escaLATion Using High-prEcision Mr-guided Radiotherapy (ESCALATE): a Phase 1 Dose Finding Trial
This trial will try higher, MRI-guided radiation doses together with standard chemotherapy for adults with resectable, locally advanced esophageal squamous cell carcinoma to see if it improves tumor control before surgery.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 30 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | UMC Utrecht Academic / other |
| Drugs / interventions | chemotherapy, radiation |
| Locations | 1 site (Utrecht, Utrecht) |
| Trial ID | NCT07359417 on ClinicalTrials.gov |
What this trial studies
This is a phase 1, single-center trial using an MR-Linac to deliver adaptive radiotherapy with stepwise dose escalation alongside the CROSS neoadjuvant chemotherapy regimen for patients with resectable, locally advanced esophageal squamous cell carcinoma. Daily MRI guidance will be used to adapt treatment planning and better spare nearby organs while escalating radiation dose above the current neoadjuvant standard. The primary focus is on safety, tolerability, and feasibility of escalating dose with careful monitoring for acute and early late toxicity, and secondary data will include tumor response and pathologic complete response at surgery. Eligible tumors must be definable on baseline MRI, and patients proceed to planned esophagectomy after completion of chemoradiotherapy per standard care. All treatment and follow-up are conducted at University Medical Center Utrecht.
Who should consider this trial
Good fit: Adults (≥18) with histologically confirmed, potentially resectable locally advanced esophageal squamous cell carcinoma who are planned for CROSS neoadjuvant chemoradiotherapy and whose tumor is visible on MRI with WHO performance status 0–2.
Not a fit: Patients with non-squamous histology, metastatic or unresectable disease, tumors not visible on MRI, or those unable to tolerate the CROSS chemotherapy regimen are unlikely to benefit from this protocol.
Why it matters
Potential benefit: If successful, MRI-guided dose escalation could increase the chance of complete tumor response and potentially improve long-term local control or organ preservation.
How similar studies have performed: MR-guided adaptive radiotherapy is an emerging technique with encouraging early targeting and safety data in other tumor sites, but dose escalation specifically for esophageal squamous cell carcinoma remains largely unproven and is being tested in this early-phase trial.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion criteria In order to be eligible for this study, a subject must meet all of the following criteria: * Histologically confirmed squamous cell carcinoma of the esophagus or GE- junction (Siewert I/II) * Potentially resectable, locally advanced esophageal tumor (cT1bN+, cT2-3, N0-3, M0) based on standard primary staging by EUS and 18F-FDG PET-CT * Scheduled to receive neoadjuvant chemoradiotherapy according to CROSS-regimen: weekly administration of carboplatin and paclitaxel for 5 weeks and concurrent radiotherapy (41.4Gy in 23 fractions, 5 days per week), followed by esophagectomy (as judged by the multidisciplinary tumor board) * Tumor length ≤ 10 cm * Age ≥ 18 years * WHO performance status 0-2 * Signed informed consent * Tumor volume that can be defined on MRI at baseline (T2w and DW-MRI) * Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations. Exclusion criteria A subject who meets any of the following criteria will be excluded from participation in this study: * Adenocarcinoma of the esophagus * Non-resectable, inoperable or metastatic squamous cell carcinoma of the esophagus or GE-junction * Siewert type III * Squamous cell carcinoma of the cervical esophagus * Prior (chemo)radiotherapy to the mediastinum * Prior esophageal surgery that impedes the ability to perform an esophagectomy * Patients with multiple primary carcinomas of the esophagus * Patients who meet exclusion criteria for MRI * Irradical endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) of primary tumor prior to start of neoadjuvant chemoradiotherapy * Pregnant or breast-feeding patients * Patients in whom it is not in their best interest to participate (in the judgment of the PI)
Where this trial is running
Utrecht, Utrecht
- University Medical Center Utrecht — Utrecht, Utrecht, Netherlands (Recruiting)
Study contacts
- Study coordinator: drs. Sanders, MD
- Email: MRGuidedRTSlokdarm@umcutrecht.nl
- Phone: +31 (0)88-755-5555
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.