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

NCT03546829 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: UPCC 08517827551
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Early Stage Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (3)

• 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

Study Arms (1)

Arm 1 - Experimental

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; Radiation: Precision hypofractionated radiation

Interventions

Vancomycin DRUG

125 mg, 4x daily for 5 weeks

Arm 1 - Experimental

Precision hypofractionated radiation 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.

Arm 1 - Experimental

Eligibility Criteria

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

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Abramson Cancer Center at Penn Medicine: lead

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Related Publications (1)

• 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.

  PMID: 40639850 DERIVED

MeSH Terms

Interventions

Vancomycin

Intervention Hierarchy (Ancestors)

Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Steven Feigenberg, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ching Lai

CONTACT

267-250-9244; ching.lai@pennmedicine.upenn.edu

RadOnc Clinical Research Unit

CONTACT

radonccru@pennmedicine.upenn.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2018
• First Posted: June 6, 2018
• Study Start: March 5, 2019
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: January 14, 2026

Record last verified: 2026-01

Locations

US (1)