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

This is a prospective, randomized, open-label, two-arm phase 2 trial that will evaluate whether the use of Pulsed Low-Dose-Rate radiation technique, as compared to standard radiation, is associated with reduced rates of clinically significant esophagitis during and following chemoradiation.

Study Overview

• Status: Recruiting
• Conditions: Esophageal Cancer; Oesophageal Cancer; GastroEsophageal Cancer
• Intervention / Treatment: Drug: Chemotherapy; Radiation: Pulsed Low-Dose-Rate (PLDR) Radiation; Procedure: Surgery; Radiation: Conventional Radiation; Drug: Induction Chemotherapy (modified FLOT or modified FOLFOX-6)

Detailed Description

PLDR radiation technique has been shown to kill cancer cells while limiting normal tissue toxicity. In PLDR, subjects receive the same total dose of radiation for each treatment, but the treatment is delivered in a series of low-dose pulses which are separated by timed pauses. Radiation given with this approach may be less toxic but appears to be equally effective. This trial will evaluate the PLDR technique in combination with standard chemotherapy as part of definitive or curative treatment for locally advanced esophageal cancer.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Medical College of Wisconsin Cancer Center Clinical Trials Office; Phone Number: 8900 866-680-0505; Email: cccto@mcw.edu

Study Locations

• United States
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • Froedtert & the Medical College of Wisconsin
      • Contact: Lindsay Puckett, MD; Phone Number: 414-805-4400; Email: lpuckett@mcw.edu
      • Principal Investigator: Lindsay Puckett, MD

Participation Criteria

Eligibility Criteria

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

Description

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.

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
Experimental: Pulsed Low-Dose-Rate Radiation (PLDR); Neoadjuvant radiation delivered in short pulses; same dose as standard chemoradiation arm.	Drug: Chemotherapy; The preferred concurrent chemoradiation is carboplatin/paclitaxel weekly.; Radiation: Pulsed Low-Dose-Rate (PLDR) Radiation; For both standard conventional radiation therapy and PLDR radiation therapy, the standard dose (5000cGy/25fx default, 4140-5040 in 23-28 fractions) should be given. Fractions should consist of 180-200 cGy per treatment. For PLDR radiation therapy, each fraction will be delivered as a series of 20 cGy (or 0.2 Gy) pulses that are separated by 3-minute time intervals.; Procedure: Surgery; Esophagectomy is not required for trial and will be administered per medical judgement of the treating physicians. Surgery will take place at the time directed by the surgeon. This typically will take place approximately 6-13 weeks after chemoradiation therapy.; Drug: Induction Chemotherapy (modified FLOT or modified FOLFOX-6); Subjects are expected to receive 2-4 months of induction chemotherapy; the interval and dosages will be determined and can be modified at the discretion of their medical oncologist. The preferred induction chemotherapies are modified FLOT or FOLFOX-6. Subjects can enroll if they receive less than 2 months of induction chemotherapy as long as they are deemed to be a candidate for concurrent chemoradiation therapy.
Experimental: Standard Chemoradiation; Standard (non-pulsed) neoadjuvant radiation; same dose as PLDR arm.	Drug: Chemotherapy; The preferred concurrent chemoradiation is carboplatin/paclitaxel weekly.; Procedure: Surgery; Esophagectomy is not required for trial and will be administered per medical judgement of the treating physicians. Surgery will take place at the time directed by the surgeon. This typically will take place approximately 6-13 weeks after chemoradiation therapy.; Radiation: Conventional Radiation; For both standard conventional radiation therapy and PLDR radiation therapy, the standard dose (5000cGy/25fx default, 4140-5040 in 23-28 fractions) should be given. Fractions should consist of 180-200 cGy per treatment.; Drug: Induction Chemotherapy (modified FLOT or modified FOLFOX-6); Subjects are expected to receive 2-4 months of induction chemotherapy; the interval and dosages will be determined and can be modified at the discretion of their medical oncologist. The preferred induction chemotherapies are modified FLOT or FOLFOX-6. Subjects can enroll if they receive less than 2 months of induction chemotherapy as long as they are deemed to be a candidate for concurrent chemoradiation therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
New prescription for narcotics	The number of subjects requiring a new prescription for narcotics.	Up to 6 weeks after radiation treatment
Increasing existing narcotics	The number of subjects increasing existing narcotics by 25%.	Up to 6 weeks after radiation treatment
Oral intake	The number of subjects transitioning from solid to liquid or liquid to no oral intake.	Up to 6 weeks after radiation therapy

Collaborators and Investigators

• Sponsor: Medical College of Wisconsin
• Investigators: Principal Investigator: Lindsay Puckett, MD, Medical College of Wisconsin

Study record dates

Study Major Dates

• Study Start (Actual): June 17, 2025
• Primary Completion (Estimated): November 1, 2030
• Study Completion (Estimated): June 1, 2032

Study Registration Dates

• First Submitted: March 26, 2025
• First Submitted That Met QC Criteria: March 26, 2025
• First Posted (Actual): April 2, 2025

Study Record Updates

• Last Update Posted (Actual): June 29, 2025
• Last Update Submitted That Met QC Criteria: June 25, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Chemoradiation; Esophageal Cancer; Oesophageal Cancer; Esophagectomy; esophagitis; GastroEsophageal Cancer; Pulsed Low-Dose-Rate Radiation; Pulsed reduced dose rate radiation; Pulsed radiation
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Esophageal Neoplasms
• Other Study ID Numbers: PRO00049620

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes