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

NCT06906887 | Recruiting Phase 2 DMC FDA Drug FDA Device

• 1 other identifier: PRO00049620
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Esophageal Cancer; Oesophageal Cancer; GastroEsophageal Cancer

Keywords

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

Outcome Measures

Primary Outcomes (3)

• 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

Study Arms (2)

Pulsed Low-Dose-Rate Radiation (PLDR)

EXPERIMENTAL

Neoadjuvant radiation delivered in short pulses; same dose as standard chemoradiation arm.

Drug: Induction Chemotherapy (modified FLOT or modified FOLFOX-6); Drug: Chemotherapy; Radiation: Pulsed Low-Dose-Rate (PLDR) Radiation; Procedure: Surgery

Standard Chemoradiation

EXPERIMENTAL

Standard (non-pulsed) neoadjuvant radiation; same dose as PLDR arm.

Drug: Induction Chemotherapy (modified FLOT or modified FOLFOX-6); Drug: Chemotherapy; Radiation: Conventional Radiation; Procedure: Surgery

Interventions

Induction Chemotherapy (modified FLOT or modified FOLFOX-6) DRUG

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.

Pulsed Low-Dose-Rate Radiation (PLDR); Standard Chemoradiation

Chemotherapy DRUG

The preferred concurrent chemoradiation is carboplatin/paclitaxel weekly.

Pulsed Low-Dose-Rate Radiation (PLDR); Standard Chemoradiation

Conventional Radiation 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.

Standard Chemoradiation

Pulsed Low-Dose-Rate (PLDR) Radiation 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.

Pulsed Low-Dose-Rate Radiation (PLDR)

Surgery PROCEDURE

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.

Pulsed Low-Dose-Rate Radiation (PLDR); Standard Chemoradiation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years.
• Stage II-IVb adenocarcinoma of the esophagus (if IVb, oligometastatic only, felt to be eligible for definitive dose CRT treatment by treating physician).
• Currently receiving or have received induction chemotherapy and planned for definitive dose chemoradiation (+/- esophagectomy).
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Adequate hematologic function within 30 days prior to registration defined as follows:
• Absolute Neutrophil Count ≥ 1,500/mcg
• Hemoglobin ≥ 8 gm/dL
• Platelets ≥ 100,000/mcL.
• 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.
• 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).
• 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.
• 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.
• 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.
• Ability to understand a written informed consent document, and the willingness to sign it.

You may not qualify if:

• Age \< 18 years.
• Extensive distant metastatic cancer, defined as \>5 metastases.
• 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).
• Prior non-approved chemotherapy for the treatment of cancer.
• Prior radiotherapy to the region of the study cancer that would result in an overlap of radiation therapy fields.
• Women must not be pregnant or breast-feeding.

Sponsors & Collaborators

• Medical College of Wisconsin: lead

Study Sites (1)

Froedtert & the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

MeSH Terms

Conditions

Esophageal Neoplasms; Esophagitis

Interventions

Induction Chemotherapy; Drug Therapy; Heart Rate; Radiation; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Gastroenteritis

Intervention Hierarchy (Ancestors)

Therapeutics; Remission Induction; Vital Signs; Physical Examination; Diagnostic Techniques and Procedures; Diagnosis; Hemodynamics; Cardiovascular Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena; Physical Phenomena

Study Officials

• Lindsay Puckett, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Medical College of Wisconsin Cancer Center Clinical Trials Office

CONTACT

866-680-0505; cccto@mcw.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: March 26, 2025
• First Posted: April 2, 2025
• Study Start: June 17, 2025
• Primary Completion (Estimated): November 1, 2030
• Study Completion (Estimated): June 1, 2032
• Last Updated: June 29, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)