Using Microbiome to Predict Durvalumab Toxicity in Post- Concurrent Chemoradiation Therapy (CCRT) NSCLC Patients

NCT04680377 | Recruiting DMC

• 1 other identifier: IIT-2019-AZmicrobiome
• Study Type: observational
• Target: 44
• Locations: 1 country
• Sites: 2

Brief Summary

This phase IV study is hoping to determine if examining the microbiome in non-small cell lung cancer participants who will receive durvalumab can predict treatment toxicity.

Conditions

NSCLC, Stage III; Locally Advanced Lung Carcinoma

Outcome Measures

Primary Outcomes (3)

• Grade 3 or higher adverse events (AE's)

  CTCAE 5.0

  Up to 18 months

• Longitudinal changes in Microbiome

  Metagenomic sequencing and taxonomic analysis

  Up to 18 months from study start

• Longitudinal changes in bacterial metabolic pathway

  Metagenomic sequencing and Kyoto Encyclopedia of Genes and Genomes (KEGG) mapping

  Up to 18 months from study start

Secondary Outcomes (3)

• Time-to-treatment withheld due to AEs

  Up to 18 months from study start

• Time to immune-mediated AEs requiring systemic intervention

  Up to 18 months from study start

• Progression free survival

  Up to 36 months from study start

Study Arms (1)

Participants receiving standard of care durvalumab

Prior to receiving treatment participants will have samples taken from three different sources to test the microbiome bacteria to determine if it will help predict toxicity to the treatment

Eligibility Criteria

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

Study Population

Participants must have histologically- or cytologically-documented NSCLC who present with locally advanced, unresectable (Stage III) disease. Participants must have not progressed following definitive, platinum-based, concurrent chemoradiation therapy.

You may qualify if:

• Ability of participant OR Legally Authorized Representative (LAR) to understand this study, and participant or LAR willingness to sign a written informed consent
• Participant is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up
• Life expectancy ≥12 weeks
• Males and females age ≥ 18 years
• Allowable type and amount of prior therapy:
• Participants must have received two or more cycles of platinum-based chemotherapy (containing etoposide, vinblastine, vinorelbine, a taxane \[paclitaxel or docetaxel\], or pemetrexed) concurrently with definitive radiation therapy (54-66 Gy)
• Eastern Cooperative Oncology Group (ECOG) Performance Status = 0 or 1
• Body weight \>30 kg (66.14 lbs)
• Participants must have histologically- or cytologically-documented NSCLC who present with locally advanced, unresectable (Stage III) disease
• Participants must have not progressed following definitive, platinum-based, concurrent chemoradiation therapy
• Adequate organ function based on laboratory results
• Women of child-bearing potential and men with partners of child-bearing potential must agree to practice sexual abstinence, or to use an acceptable form of contraception for the duration of study participation, and for the time specified following completion of therapy

You may not qualify if:

• Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or if the participant is in the follow-up period of an interventional study
• Participation in another clinical study with an investigational product during the last 4 weeks prior to enrollment on this study
• Prior randomization or treatment in a previous durvalumab clinical study regardless of treatment arm assignment
• Mixed small cell and non-small cell lung cancer histology
• Participants who receive sequential chemoradiation therapy for locally advanced NSCLC
• Participants with locally advanced NSCLC who have progressed whilst definitive platinum based, concurrent chemoradiation therapy
• Receipt of any investigational drug within 4 weeks prior to the first dose of durvalumab; and in the case of monoclonal antibodies (not immunotherapy) 6 weeks prior to the first dose of durvalumab
• Participants who have received prior anti-programmed death (PD)-1, anti- programmed death ligand (PD-L)1 or anti- cytotoxic T-lymphocyte-associated protein (CTLA)-4
• Participants who have received prior immunotherapy
• Receipt of live attenuated vaccine within 30 days prior to the first dose of investigational product (IP). Note: Participants, if enrolled, should not receive live vaccine whilst receiving durvalumab and up to 30 days after the last dose of IP
• Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab
• Any grade pneumonitis from prior chemoradiation therapy
• Active infection
• Recent major surgery within 28 days prior to the first dose of study therapy
• Active or prior documented autoimmune or inflammatory disorders

Sponsors & Collaborators

• Jun Zhang, MD, PhD: lead
• Rhode Island Hospital: collaborator

Study Sites (2)

The University of Kansas Cancer Center, Westwood Campus

Kansas City, Kansas, 66205, United States

RECRUITING

Rhode Island Hospital, Brown University

Providence, Rhode Island, 02905, United States

NOT YET RECRUITING

Related Publications (2)

• Swami U, Zakharia Y, Zhang J. Understanding Microbiome Effect on Immune Checkpoint Inhibition in Lung Cancer: Placing the Puzzle Pieces Together. J Immunother. 2018 Oct;41(8):359-360. doi: 10.1097/CJI.0000000000000232.

  PMID: 29781826 BACKGROUND

• Strouse C, Mangalam A, Zhang J. Bugs in the system: bringing the human microbiome to bear in cancer immunotherapy. Gut Microbes. 2019;10(2):109-112. doi: 10.1080/19490976.2018.1511665. Epub 2018 Sep 5.

  PMID: 30183502 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

nasal and buccal swabs, and stool

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Jun Zhang, MD, PhD

  The University of Kansas Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

KUCC Navigation

CONTACT

9135883671; kucc_Navigation@kumc.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: December 17, 2020
• First Posted: December 23, 2020
• Study Start: April 12, 2021
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: May 8, 2024

Record last verified: 2024-05

Locations

US (2)