PULSAR in Systemic Therapy for Pancreatic Cancer

NCT07269626 | Recruiting Phase 2 DMC

• 2 other identifiers: PARIS-PC2025-09-076
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

Brief Summary

Pancreatic cancer remains one of the malignancies with the lowest survival rates, largely due to late-stage diagnosis and the difficulty of achieving curative resection. A substantial proportion of patients present with locally advanced, unresectable disease at the time of diagnosis, making intensive systemic therapy the current standard of care. For selected patients, radiation therapy (RT) is integrated to improve local control. Local progression in the pancreas can lead to severe complications, including intractable pain, gastric outlet obstruction, and biliary obstruction, which ultimately contribute to morbidity, deteriorating quality of life, and reduced overall survival. Therefore, effective local therapy remains a critical component of comprehensive management. However, delivering high-dose radiation to pancreatic tumors is particularly challenging because the pancreas is anatomically surrounded by radiation-sensitive organs such as the stomach, duodenum, liver, kidneys, and small bowel. Conventional RT and stereotactic body RT (SBRT) have both been limited by gastrointestinal toxicity, making substantial dose escalation difficult and resulting in modest local control outcomes. Previous studies combining systemic therapy with radiotherapy have shown signals of improved local progression-free survival (LPFS) and progression-free survival (PFS). Still, results have been inconsistent across trials, highlighting the need for rigorous clinical evaluation of the true therapeutic benefit of integrating radiotherapy with systemic treatment in this disease population. Conventional RT often requires several weeks of treatment, during which interruption or modification of systemic therapy may increase the risk of distant progression. SBRT shortens the treatment duration but exposes patients to large per-fraction radiation doses, increasing the risk of gastrointestinal injury and limiting eligibility to highly selected cases. Against this backdrop, the recently proposed PULSAR (Personalized Ultra-fractionated Stereotactic Adaptive Radiotherapy) strategy offers an innovative approach to overcome the limitations of traditional radiation therapy. PULSAR delivers 3-4 ultra-fractionated, stereotactic "pulses" of radiation at intervals of approximately 3-4 weeks. Each pulse is delivered with adaptive planning based on interval changes in tumor anatomy and nearby organs at risk. This wide spacing minimizes interruptions to systemic therapy and provides time for tumor shrinkage and normal tissue recovery before subsequent pulses. These features may reduce toxicity while enabling more effective dose delivery to the tumor. Such advantages are particularly relevant for pancreatic tumors located adjacent to sensitive gastrointestinal structures, potentially improving upon the limitations of SBRT. The proton beam therapy offers additional precision through the physical characteristics of proton beams, particularly the Bragg peak, which allows for high-dose deposition within the tumor while sparing surrounding normal tissues. The combination of proton therapy with the PULSAR framework may provide a highly targeted, organ-preserving local treatment strategy for a disease known for its complex anatomy and therapeutic difficulty. Within this context, a clinical strategy that integrates intensive first-line systemic therapy followed by PULSAR-based adaptive proton radiotherapy holds promising potential. Systemic therapy may reduce tumor burden, after which personalized, pulse-based proton irradiation can be tailored according to treatment response, delivering biologically effective doses to maximize local control while maintaining systemic treatment intensity. This approach may enhance survival outcomes by addressing both local disease control and risk of distant metastasis. In summary, given the critical need to improve survival in locally advanced pancreatic cancer and the inherent limitations of existing radiation approaches, combining PULSAR-guided adaptive proton therapy with contemporary systemic therapy represents a compelling new treatment paradigm. This study aims to systematically evaluate the clinical feasibility, safety, and therapeutic effectiveness of this integrated approach in patients with locally advanced pancreatic cancer.

Conditions

Locally Advanced Pancreatic Ductal Adenocarcinoma; Borderline Resectable Pancreatic Ductal Adenocarcinoma; Oligometastatic Pancreatic Ductal Adenocarcinoma

Keywords

Pancreatic cancer; proton beam radiotherapy; PULSAR

Outcome Measures

Primary Outcomes (3)

• progression-free survival at 1-year after enrollment

  PFS is defined as the period from the date of the first PULSAR session to the date of documented disease progression, death, or last follow-up, whichever occurs first.

  PFS rate at 1 year is defined as the proportion of patients who have not experienced disease progression or death within 12 months from study enrollment.

• Progression-free survival

  Defined as the period from the date of the study enrollment to the date of documented disease progression, death, or last follow-up, whichever occurs first.

  at 1 year-progression-free survival (PFS_, defined as the proportion of patients who have not experienced disease progression or death within 12 months from study enrollment.

• Local control (LC)

  LC is defined as proportion of patients without local tumor progression based on RECIST version 1.1 criteria.

  The 2-year LC rate will be defined as the proportion of patients who remain free from local tumor progression at 2 years after study enrollment.

Secondary Outcomes (2)

• Overall survival

  OS rate at 2-year, is defined as the proportion of patients who remain alive at 2 years after study enrollment.

• Objective Response Rate (ORR)

  ORR will be assessed according to RECIST version 1.1 at 1 month after completion of PULSAR (with an allowable window of up to 8 weeks).

Study Arms (1)

PULSAR

EXPERIMENTAL

Standard systemic therapy with PULSAR

Radiation: Personalized Ultrafractionated Adaptive Radiotherapy

Interventions

Personalized Ultrafractionated Adaptive Radiotherapy RADIATION

Proton therapy will be delivered at 12 gray (relative biological effectiveness, RBE) per fraction, administered once every 3 to 4 weeks, for a total of 2 to 3 fractions.

PULSAR

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 19 years.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Histologically confirmed pancreatic ductal adenocarcinoma.
• Disease extent classified as borderline resectable, locally advanced, or oligometastatic disease (defined as ≤ 3 metastatic lesions) at the time of staging evaluation.
• Completion of at least 2-4 cycles of first-line systemic therapy (FOLFIRINOX, gemcitabine/nab-paclitaxel, or NALIRIFOX) without evidence of distant progression.
• Presence of a lesion suitable for radiotherapy, as determined by the investigator, and measurable disease per RECIST 1.1 criteria.
• Ability to understand the study requirements and voluntarily provide written informed consent.

You may not qualify if:

• Pregnant or breastfeeding women.
• Presence of brain metastases or leptomeningeal disease.
• History of prior radiotherapy to the intended treatment area.
• Significant comorbid conditions that may interfere with study participation or the ability to safely receive study treatment, as determined by the investigator (e.g., uncontrolled infection, congestive heart failure, clinically significant arrhythmia, or severe psychiatric illness).
• Patients deemed unlikely to comply with study procedures or follow-up requirements.
• Any condition that, in the opinion of the principal investigator or treating physician, makes the patient inappropriate for participation in this trial.

Sponsors & Collaborators

• Samsung Medical Center: lead

Study Sites (1)

Samsung Medical Center

Seoul, Select Province/State, 06351, South Korea

RECRUITING

MeSH Terms

Conditions

Pancreatic Neoplasms

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Study Officials

• Jeong Il Yu

  Samsung Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jeong Il Yu, MD, PhD

CONTACT

+82234109598; ro.yuji651@gmail.com

Hee Chul Park, MD, PhD

CONTACT

02-3410-2612; jeongil.yu@samsung.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Standard systemic therapy with PULSAR

Study Record Dates

• First Submitted: November 25, 2025
• First Posted: December 8, 2025
• Study Start: November 14, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: December 8, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)