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

Official title

Using Microbiome to Predict Durvalumab Toxicity in Post-CCRT NSCLC Patients (Microdurva)

Overview

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.

Primary outcome measures

• Grade 3 or higher adverse events (AE's) [Time frame: Up to 18 months]
• Longitudinal changes in Microbiome [Time frame: Up to 18 months from study start]
• Longitudinal changes in bacterial metabolic pathway [Time frame: Up to 18 months from study start]

Secondary outcome measures (3)

• Time-to-treatment withheld due to AEs [Time frame: Up to 18 months from study start]
• Time to immune-mediated AEs requiring systemic intervention [Time frame: Up to 18 months from study start]
• Progression free survival [Time frame: Up to 36 months from study start]

Eligibility criteria

Inclusion criteria

• 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

Exclusion criteria

• 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 unresolved toxicity CTCAE ≥ Grade 2 from the prior chemoradiation / anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
• 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
• History of primary immunodeficiency
• History of another primary malignancy
• History of allogenic organ transplantation/organ transplant that requires therapeutic immunosuppression
• History of leptomeningeal carcinomatosis
• Participants with active ventricular arrhythmia requiring medication
• Uncontrolled intercurrent illness
• Participants who have progressed following definitive, platinum-based, concurrent chemoradiation therapy
• Known allergy or hypersensitivity to durvalumab or any of durvalumab's excipients
• Psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the patient to give written informed consent

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

United States · 2 centers

• The University of Kansas Cancer Center, Westwood Campus — Kansas City
• Rhode Island Hospital, Brown University — Providence

Publications

• 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
• 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

Identifiers

NCT: NCT04680377 · IIT-2019-AZmicrobiome

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗