Pulsed low-dose-rate radiation plus chemotherapy versus standard chemoradiation for esophageal cancer

PULSO Trial: Pulsed Low-Dose-Rate (PLDR) Radiation Chemoradiation (CRT) vs. Standard CRT for Esophageal Cancer

This trial will test whether delivering radiation as pulsed low-dose-rate together with chemotherapy reduces serious esophagitis compared with standard chemoradiation in adults with locally advanced esophageal adenocarcinoma.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Medical College of Wisconsin (Academic / other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 1 site (Milwaukee, Wisconsin)
• Trial ID: NCT06906887 on ClinicalTrials.gov

What this trial studies

This randomized, open-label phase 2 trial assigns adults with locally advanced esophageal adenocarcinoma to receive either pulsed low-dose-rate (PLDR) radiation or conventional radiation, each given with standard concurrent chemotherapy and possible esophagectomy. PLDR delivers the same total radiation dose as standard treatment but in a series of small pulses separated by timed pauses, which may reduce normal tissue injury. The trial's primary focus is rates of clinically significant esophagitis during and after chemoradiation, with safety, feasibility, and oncologic outcomes also monitored. Eligible participants must have ECOG 0–2 and adequate blood, liver, and kidney function and will be treated at Froedtert & the Medical College of Wisconsin.

Who should consider this trial

Good fit: Adults (≥18) with stage II–IVb (oligometastatic only) esophageal adenocarcinoma planned for definitive chemoradiation, who have ECOG 0–2 and meet organ function requirements, are the intended participants.

Not a fit: Patients with widespread metastatic disease, ECOG >2, significant organ dysfunction, or non-adenocarcinoma histology are unlikely to receive benefit from this approach.

Why it matters

Potential benefit: If successful, PLDR could reduce severe esophagitis and make chemoradiation easier to complete, improving symptoms and quality of life.

How similar studies have performed: Early preclinical work and small clinical reports indicate PLDR can spare normal tissues while maintaining tumor control, but randomized data in esophageal cancer are limited.

Eligibility criteria

Inclusion Criteria:

A potential study subject who meets all of the following inclusion criteria is eligible to participate in the study.

1. Age ≥ 18 years.
2. Stage II-IVb adenocarcinoma of the esophagus (if IVb, oligometastatic only, felt to be eligible for definitive dose CRT treatment by treating physician).
3. Currently receiving or have received induction chemotherapy and planned for definitive dose chemoradiation (+/- esophagectomy).
4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
5. Adequate hematologic function within 30 days prior to registration defined as follows:

   1. Absolute Neutrophil Count ≥ 1,500/mcg
   2. Hemoglobin ≥ 8 gm/dL
   3. Platelets ≥ 100,000/mcL.
6. Adequate renal function within 30 days prior to registration, defined as a creatinine clearance of ≥ 50 ml/min as calculated by the Cockcroft-Gault equation.
7. Adequate hepatic function within 30 days prior to registration, defined as total bilirubin ≤ 1.5 x ULN

   a. Note: patients with known Gilbert Syndrome can have a total bilirubin \< 2.5 x upper limit of normal (ULN).
8. Female patients \<65 years of age and of childbearing potential must have a negative serum/urine pregnancy test within 14 days prior to study entry. A female not of childbearing potential is one who has undergone a hysterectomy, bilateral oophorectomy, tubal ligation, or who has had no menses for 12 consecutive months.
9. Patients of reproductive potential must agree to use effective contraception for the duration of study treatment. Effective contraception includes oral contraceptives, implantable hormonal contraception, double-barrier method, or intrauterine device.
10. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
11. Ability to understand a written informed consent document, and the willingness to sign it.

Exclusion Criteria:

A potential study subject who meets any of the following exclusion criteria is ineligible to participate in the study.

1. Age \< 18 years.
2. Extensive distant metastatic cancer, defined as \>5 metastases.
3. Recurrent esophageal cancer.

   a. Note: prior or concurrent malignancies are allowed if they do not impact the study's primary endpoint (i.e., treatment-associated toxicity).
4. Prior non-approved chemotherapy for the treatment of cancer.
5. Prior radiotherapy to the region of the study cancer that would result in an overlap of radiation therapy fields.
6. Women must not be pregnant or breast-feeding.

Where this trial is running

Milwaukee, Wisconsin

• Froedtert & the Medical College of Wisconsin — Milwaukee, Wisconsin, United States (Recruiting)

Study contacts

• Principal investigator: Lindsay Puckett, MD — Medical College of Wisconsin
• Study coordinator: Medical College of Wisconsin Cancer Center Clinical Trials Office

Conditions Esophageal Cancer; Oesophageal Cancer; GastroEsophageal Cancer; Pulsed Low-Dose-Rate Radiation; Chemoradiation; esophagitis; Esophagectomy; Pulsed reduced dose rate radiation