MR-Guided Radiotherapy Dose Escalation Trial 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

MR-Guided Radiotherapy Dose Escalation Trial for Esophageal Squamous Cell Carcinoma (NCT07359417) is a Phase 1 interventional studying Esophageal Squamous Cell Carcinoma (ESCC) and Esophageal Cancer, Squamous Cell, sponsored by UMC Utrecht. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

About This Trial

SUMMARY Rationale: Esophageal cancer (EC) is the seventh most frequently diagnosed cancer and the sixth leading cause of cancer-related death worldwide. As a result of the late onset of symptoms, most patients with EC present in an advanced stage with a corresponding poor prognosis. Poor disease outcome after surgery alone (5-yr overall survival between 25-40%) prompted many researchers to explore neoadjuvant chemoradiotherapy (nCRT) or neoadjuvant or perioperative chemotherapy (nCT/pCT) approaches. nCRT has led to pathological complete response (pCR) rate in squamous cell EC of almost 50%. Patients with a pCR have a favorable prognosis with 5-year OS \>50%. In addition, patients who will achieve a pCR might be candidates for an organ preserving treatment strategy. Current standard nCRT consists of a relatively low dose of radiation compared to other tumors in the same area. The investigators hypothesize that increasing the dose of radiation will lead to increased local tumor control and pCR rates. Objective: The main objective of this study is to determine the maximum tolerated dose (MTD) of 2-fraction boost MRI-guided radiotherapy (MRgRT) for patients with SCC following CROSS therapy. The secondary objectives are feasibility, non-dose limiting toxicity, oncological outcomes and to explore variables for early response evaluation. Study design: 6+3 dose-escalation design with 3 radiotherapy dose levels. Study population: Patients with a resectable squamous cell esophageal carcinoma who are eligible for nCRT, surgery and MRgRT. Intervention: 2 sequential, homogenous boost fractions of 4-7 Gy on the gross tumor volume (GTV) in the week following CROSS using MR-guided online adaptive radiotherapy on the MR-linac. Start in dose level 0, of 2 x 5Gy boost per patient, and if safe this is increased step-wise to a maximum dose level 2 of 2 x 7Gy per patient. Main study parameters/endpoints: The primary endpoint is the incidence of a dose limiting toxicity (DLT). Early DLT is defined as radiation induced esophageal fistula/ perforation/ hemorrhage/ necrosis or tracheal, bronchial or bronchopleural fistula/tracheal or bronchopulmonary hemorrhage grade ≥ 3 or any non-hematological grade 4 toxicity according to Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0 occurring within 14 weeks after the start of radiotherapy and before surgery or the postponing of surgery \> 14 weeks after the end of radiotherapy due to any grade of treatment-related toxicity. Subacute DLT is defined as peri- and/or postoperative complications occurring within 30 days after surgery, defined as postoperative anastomotic leakage or pneumonitis ≥ 3b according to Clavien-Dindo. Secondary endpoints are non-DLT toxicity, the technical feasibility of dose delivery, perioperative complications, and oncological outcomes including R0 resection rate, histopathological tumor response, local and regional recurrence and death from any cause. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The benefits for the patients may include higher probability of complete pathological response that initially leads to increased survival and could eventually result in organ-sparing treatment programs. Compared to standard treatment, the CROSS regimen including the sequential boost will take 2 days extra in the final week of CROSS. Possible risks include higher radiation toxicity and surgical complication rates. However, it is expected this increase to be minor, for the investigators will use dose constraints on organs at risk, which are associated with low radiation-induced toxicity, and they will not be exceeded.

What Stage of Research Is This?

Phase 1 trials test a new treatment for the first time in humans, focusing on safety, dosing, and how the body processes the drug. For Esophageal Squamous Cell Carcinoma (ESCC), a Phase 1 study typically enrolls a small number of participants — often healthy volunteers or patients who have exhausted standard treatment options. Phase 1 results determine whether a treatment moves into larger Phase 2 efficacy studies.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

With a target enrollment of 30 participants, this is a small study — typical of early-phase research, rare-disease trials, or pilot studies designed to generate preliminary signal before a larger study is launched.

Who May Be Eligible (Plain English)

Inclusion criteria In order to be eligible for this study, a subject must meet all of the following criteria: - diagnosed by tissue sample (biopsy-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 willing to sign a consent form - 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 willing to sign a consent form 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 ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language

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)

Treatments Being Tested

OTHER

Radiation: MRI guided radiotherapy

MRI guided radiotherapy

Locations (1)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

University Medical Center Utrecht

Utrecht, Utrecht, Netherlands

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT07359417), the sponsor (UMC Utrecht), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT07359417 clinical trial studying?

Who can participate in NCT07359417?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT07359417?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT07359417. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT07359417. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-05-08 · Data from ClinicalTrials.gov.