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

NCT ID: NCT06906887

Last Updated: 2025-06-29

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-06-17
• Study Completion Date: 2032-06-01

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.

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.

Conditions

Esophageal Cancer; Oesophageal Cancer; GastroEsophageal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pulsed Low-Dose-Rate Radiation (PLDR)

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

Group Type: EXPERIMENTAL

Induction Chemotherapy (modified FLOT or modified FOLFOX-6)

Intervention Type: 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.

Chemotherapy

Intervention Type: DRUG

The preferred concurrent chemoradiation is carboplatin/paclitaxel weekly.

Pulsed Low-Dose-Rate (PLDR) Radiation

Intervention Type: 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.

Surgery

Intervention Type: 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.

Standard Chemoradiation

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

Group Type: EXPERIMENTAL

Induction Chemotherapy (modified FLOT or modified FOLFOX-6)

Intervention Type: 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.

Chemotherapy

Intervention Type: DRUG

The preferred concurrent chemoradiation is carboplatin/paclitaxel weekly.

Conventional Radiation

Intervention Type: 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.

Surgery

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

Chemotherapy

The preferred concurrent chemoradiation is carboplatin/paclitaxel weekly.

Intervention Type: DRUG

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.

Intervention Type: 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.

Intervention Type: RADIATION

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.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

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

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medical College of Wisconsin

OTHER

Sponsor Role: lead

Responsible Party

Lindsay Puckett, MD

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lindsay Puckett, MD

Role: PRINCIPAL_INVESTIGATOR

Medical College of Wisconsin

Locations

Froedtert & the Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Medical College of Wisconsin Cancer Center Clinical Trials Office

Role: CONTACT

cccto@mcw.edu

866-680-0505 ext. 8900

Facility Contacts

Lindsay Puckett, MD

Role: primary

lpuckett@mcw.edu

414-805-4400

Other Identifiers

PRO00049620

Identifier Type: -

Identifier Source: org_study_id