Safety Trial of Antimicrobial Therapy and Precision Radiation Therapy in Patients With Oligoprogressive Non-small Cell Lung Cancer

The first phase of this study was an open label, randomized pilot study. Enrollment for this phase is now complete.

The second phase is a single arm phase 1 safety study. Patients planned to undergo precision hypofractionated radiation to all sites of oligoprogression will receive vancomycin for 1 week before RT and for 1 month after start of RT, and asked to provide stool and blood samples as outlined in the Safety Trial study table.

Study Overview

• Status: Recruiting
• Conditions: Early Stage Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Vancomycin; Radiation: Precision hypofractionated radiation

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Ching Lai; Phone Number: 267-250-9244; Email: Ching.Lai@pennmedicine.upenn.edu
• Study Contact Backup: Name: RadOnc Clinical Research Unit; Email: radonccru@pennmedicine.upenn.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania
      • Contact: Ching Lai; Phone Number: 267-250-9244; Email: Ching.Lai@pennmedicine.upenn.edu
      • Principal Investigator: Steven Feigenberg, MD
      • Contact: RadOnc Clinical Research Unit; Email: radonccru@pennmedicine.upenn.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Randomized Pilot Inclusion

• Patients planned to receive Stereotactic Body Radiotherapy (SBRT) to a biopsy-proven or clinically-suspected NSCLC
• Age >18 years' old
• Patient capable of giving informed consent

Randomized Pilot Exclusion

• Use of antibiotics, antifungal, antivirals or antiparasitics during the 4 weeks prior to registration
• Active infection with oral temperature >100°F
• Use of corticosteroids, methotrexate or immunosuppressive drugs during the 4 weeks prior to registration
• Use of chemotherapy during the 4 weeks prior to radiotherapy or during radiotherapy. Chemotherapy cannot begin before the collection of the 30-day post treatment sample (S4).
• Documented history of HIV, HBV or HCV
• Active uncontrolled gastrointestinal disorders such as inflammatory bowel disease, moderate/severe irritable bowel syndrome, persistent, infectious gastroenteritis, colitis or gastritis, persistent or chronic diarrhea of unknown etiology, Clostridium Difficile infection (within 2 years of lung cancer diagnosis) or Helicobacter Pylori infection (untreated)
• Major surgery of the GI tract, with the exception of cholecystectomy and appendectomy, in the past five years. Any major bowel resection at any time
• Patients on anti-diarrheal medications
• Patients on probiotics

Safety Trial Inclusion

• Patients planned to receive precision hypofractionated radiation (SBRT or an ablative dose of radiation is used if SBRT is not appropriate or if insurance does not approve - i.e. > 30 Gy in 10 fraction equivalent) to all sites of oligoprogressive NSCLC who progressed after 1st line systemic therapy for metastatic disease which included immunotherapy or a tyrosine kinase inhibitors (TKI) for NSCLC
• The number of sites of progression are < 5 sites.
• Age >18 years' old
• Patient capable of giving informed consent

Safety Trial Exclusion

• Evidence of untreated CNS or leptomeningeal disease
• Use of antibiotics, antifungal, antivirals or antiparasitics during the 4 weeks prior to registration
• Active infection with oral temperature >100°F
• Use of oral corticosteroids, methotrexate or immunosuppressive drugs during the 4 weeks prior to registration
• Use of chemotherapy during the 4 weeks prior to radiotherapy or during radiotherapy. Chemotherapy cannot begin before the collection of the 30-day post treatment sample (S3).
• Documented history of HIV, HBV or HCV
• Patients on daily anti-diarrheal medications
• Use of probiotics during the 4 weeks prior to radiotherapy or during radiotherapy

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: Arm 1 - Experimental; Patients planned to undergo precision hypofractionated radiation to all sites of oligoprogression will receive vancomycin for 1 week before RT and for 1 month after start of RT, and asked to provide stool and blood samples as outlined in the Safety Trial study table.	Drug: Vancomycin; 125 mg, 4x daily for 5 weeks; Radiation: Precision hypofractionated radiation; Patients planned to undergo precision hypofractionated radiation to all sites of oligoprogression and will receive vancomycin for 1 week before RT and for 1 month after start of RT, and asked to provide stool and blood samples as outlined in the Safety Trial study table.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Randomized Pilot: Th1 immune response measured by cytokine expression (IFN gamma).	The primary endpoint is IFN-gamma cytokine expression at Day 30 (+/- 2) collection compared to the pre-radiation level. It will be analyzed using generalized linear mixed models.	2 years
Randomized Pilot: the safety of the addition of vancomycin to Stereotactic Body Radiotherapy	The primary safety endpoint is uncontrolled diarrhea, as defined by CTCAE v4.0 > or = grade 3 (Increase of >=7 stools per day over baseline; incontinence; hospitalization indicated; severe increase in ostomy output compared to baseline; limiting self-care ADL). This will be evaluated during treatment and at 1 month, 3 months, 6 months and 12 months.	2 years
Safety Trial: the safety of the addition of vancomycin to precision hypofractionated radiation	Safety Trial: The primary safety endpoint is uncontrolled diarrhea, as defined by CTCAE v5.0 > or = grade 3 Increase of >=7 stools per day over baseline; hospitalization indicated; severe increase in ostomy output compared to baseline; limiting self care ADL). This will be evaluated weekly during vancomycin use and RT, at 1 month post-vancomycin, 3 months post-vancomycin, 6 months post-vancomycin and 12 months post-vancomycin.	3 years

Collaborators and Investigators

• Sponsor: Abramson Cancer Center at Penn Medicine
• Investigators: Principal Investigator: Steven Feigenberg, MD, University of Pennsylvania

Publications and helpful links

General Publications

• Feigenberg SJ, Costabile F, Tanes C, Bittinger K, O'Connor R, Agarwal D, Skoufos G, Salaris S, Hatzigeorgiou A, Kostopoulos N, Lloyd S, Friedes C, Chen L, Yegya-Raman N, Cengel K, Levin W, Valentic B, Quarton T, Shestov AA, Berman A, Bradley J, Maity A, Koumenis C, Ben-Josef E, Facciabene A. Enhancing outcomes in medically inoperable early-stage NSCLC with gut-targeted antibiotics and stereotactic body radiotherapy: results from a randomized pilot study. J Immunother Cancer. 2025 Jul 10;13(7):e011356. doi: 10.1136/jitc-2024-011356.

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2019
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: May 23, 2018
• First Submitted That Met QC Criteria: May 23, 2018
• First Posted (Actual): June 6, 2018

Study Record Updates

• Last Update Posted (Estimated): January 14, 2026
• Last Update Submitted That Met QC Criteria: January 13, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Peptides; Amino Acids, Peptides, and Proteins; Carbohydrates; Glycoconjugates; Glycopeptides; Vancomycin
• Other Study ID Numbers: UPCC 08517; 827551 (Other Identifier: University of Pennsylvania IRB)

Drug and device information, study documents

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