Predicting durvalumab toxicity using microbiome analysis in lung cancer patients

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

This study is testing if the bacteria in the gut can help predict how bad the side effects will be for lung cancer patients taking durvalumab after their treatment.

Quick facts

• Study type: Observational
• Enrollment: 44 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Kansas Medical Center (Academic / other)
• Drugs / interventions: durvalumab, chemotherapy, immunotherapy, radiation
• Locations: 2 sites (Kansas City, Kansas and 1 other locations)
• Trial ID: NCT04680377 on ClinicalTrials.gov

What this trial studies

This observational study aims to investigate whether the microbiome can be used to predict the toxicity of durvalumab in patients with stage III non-small cell lung cancer (NSCLC) who have undergone concurrent chemoradiation therapy. Participants will be monitored for treatment-related side effects while their microbiome composition is analyzed. The study seeks to establish a correlation between microbiome profiles and the severity of toxicity experienced during treatment. By understanding these relationships, the study hopes to improve patient management and treatment outcomes.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with locally advanced, unresectable stage III NSCLC who have completed specific prior chemotherapy and radiation therapy.

Not a fit: Patients with early-stage NSCLC or those who have not received the required prior treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to personalized treatment plans that minimize toxicity for lung cancer patients receiving durvalumab.

How similar studies have performed: While the use of microbiome analysis in predicting treatment outcomes is an emerging field, this specific approach to durvalumab toxicity prediction is novel and has not been extensively tested in prior studies.

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

Where this trial is running

Kansas City, Kansas and 1 other locations

• The University of Kansas Cancer Center, Westwood Campus — Kansas City, Kansas, United States (Recruiting)
• Rhode Island Hospital, Brown University — Providence, Rhode Island, United States (Not_yet_recruiting)

Study contacts

• Principal investigator: Jun Zhang, MD, PhD — The University of Kansas Cancer Center
• Study coordinator: KUCC Navigation

Conditions NSCLC, Stage III; Locally Advanced Lung Carcinoma