Feasibility Study of Personalized Ultra-fractionated Stereotactic Ablative Radiotherapy (PULSAR) for Cancers of the Central Lung

The objective of this study is to enhance the safety profile of SAbR in ultra-central tumors of the lung (primary or metastatic) without compromising its effectiveness.

Study Overview

• Status: Recruiting
• Conditions: Metastasis; Cancer, Lung
• Intervention / Treatment: Radiation: Personalized Ultra-fractionated stereotactic ablative radiotherapy (PULSAR)

Detailed Description

This will be achieved by demonstrating the feasibility of applying adaptive radiation therapy given in PULSAR fractionation and using a 1.5T MR-guided linac system with real-time motion monitoring (Unity, Elekta). The hypothesis is that safety can be improved through: (1) better visualization of tumors, leading to less uncertainty when delineating GTVs; (2) reduced margins for setup, motion, or other sources of uncertainty; and (3) improved normal tissue healing between radiation fractions. To achieve this, we propose a personalized ultrafractionated stereotactic adaptive radiotherapy (PULSAR) delivery schedule, administering 5 fractions total, given as one fraction every 3 weeks (Fig. 3) and using MRI-guided adaptive treatment planning.

This study is single arm in nature and in the feasibility phase

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: SARAH NEUFELD, MS, MBA; Phone Number: 214-645-8525; Email: sarah.hardee@UTSouthwestern.edu
• Study Contact Backup: Name: KENNETH WESTOVER, MD, PhD; Phone Number: 214 645 0323; Email: Kenneth.Westover@UTSouthwestern.edu

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75390
      • Recruiting
      • University of Texas Southwestern Medical Center
      • Contact: SARAH NEUFELD SUPERVISOR OF CLINICAL RESEARCH, MS, MBA; Phone Number: 214 648 1836
      • Contact: Email: Sarah.Hardee@UTSouthwestern.edu
      • Principal Investigator: KENNETH WESTOVER, MD, PhD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age ≥ 18 years of age.
2. Histologically proven diagnosis of cancer. At a minimum, the lung tumor in consideration for treatment must be clinically judged as related to the biopsied site.
3. Stage: Tumor (ITV) 1.5 - 5 cm in maximum diameter.
4. Tumor entirely within the 2 cm "central zone" or within 1 cm of the mediastinum, esophagus or proximal bronchial tree by investigator assessment.
5. Zubrod/ECOG Performance Status 0-2 within 30 days prior to registration.
6. Ability to tolerate MRI.
7. All men, as well as women of child-bearing potential* must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) from the time of consent, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

Note: A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).

Exclusion Criteria:

1. Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields.
2. Plans for the patient to receive other local therapy in lung (including standard fractionated radiotherapy and/or surgery) while on this study, except at disease progression.
3. Females of reproductive potential who are not using an effective method of birth control and females who are pregnant or breastfeeding or have a positive (urine or serum) pregnancy test prior to study entry.
4. Prior administration of anti-VEGF (vascular endothelial growth factor) therapy within 1 year.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Feasibility; Patients treated with PULSAR will undergo treatment over a total duration of 2-5 months with 3-4 weeks between each fraction. PULSAR treatments completed within 6 months will be acceptable if treatment breaks are required. In the event of a complete response between fractions, remaining fractions will be withheld at the discretion of the treating physician. Treatment may also be terminated for selected grade 3 or higher AEs. Treatment may also be terminated for regional or systemic progression detected during the PULSAR treatment interval.

Radiation: Personalized Ultra-fractionated stereotactic ablative radiotherapy (PULSAR); Radiation Therapy Prescription Dose: A dose of 40-50 Gy in 5 fractions prescribed to the PTV will be used for all cases

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy- Survivability and response	Rates of overall response will be assessed by RECIST criteria.Efficacy will be compared between PULSAR and historical controls from HILUS using ANOVA and chi-square test. Kaplan-Meier methods will be used to estimate progression-free survival, time to subsequent SABR, overall survival, clinical benefit rate, time to treatment discontinuation, duration of response, and time to new metastases. Response duration will be summarized for patients who responded. Descriptive summary statistics such as median and interquartile range (25% and 75% percentiles) will be used.	4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Tumor Volume	Change in tumor volume will be measured by comparing pre-treatment tumor volume to during-treatment tumor volumes as measured by MRI and will be analyzed using an independent t-test.	1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dosimetry	Dosimetry will be compared for relevant OARs, including heart, esophagus, and lung, and will be analyzed using an independent t-test.	1 year

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Collaborators: Elekta Limited
• Investigators: Principal Investigator: KENNETH WESTOVER, MD, PhD, UT Southwestern Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): September 19, 2025
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: November 26, 2024
• First Submitted That Met QC Criteria: November 26, 2024
• First Posted (Actual): December 2, 2024

Study Record Updates

• Last Update Posted (Actual): November 10, 2025
• Last Update Submitted That Met QC Criteria: November 6, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: lung; NSCLC; cancer; metastasis; non small cell lung cancer; PULSAR; central lumg
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplastic Processes; Carcinoma, Bronchogenic; Bronchial Neoplasms; Pathological Conditions, Signs and Symptoms; Neoplasms; Lung Neoplasms; Neoplasm Metastasis; Carcinoma, Non-Small-Cell Lung; Carbohydrates; Polysaccharides; Glucans; Dextrans; DEAE-Dextran
• Other Study ID Numbers: STU-2024-1215

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No