Quick Start Durvalumab Following Chemoradiation for Stage III Nonsmall Cell Lung Cancer

Official title

Phase II Pilot Study of Quick Start Durvalumab Following Chemoradiation for Stage III Nonsmall Cell Lung Cancer

Overview

This research study aims to determine what effects (good and bad) Durvalumab has on participants and their cancer with a "quick start" of Durvalumab within 14 days of finishing chemotherapy and radiation. The study will also determine the logistic barriers to the quick start of Durvalumab.

Detailed description

Primary Objective: Assess the treatment fidelity for early Durvalumab initiation (i.e., within 14 days after the last day of radiation therapy) following chemoradiation for unresectable Stage II or Stage III nonsmall cell lung cancer.

Secondary Objectives:

* Assess the treatment fidelity for very early Durvalumab initiation (i.e., within seven days after the last day of radiation therapy) following chemoradiation for unresectable Stage II or Stage III nonsmall cell lung cancer. * Assess barriers to earlier Durvalumab initiation following chemoradiation for unresectable Stage II or Stage III nonsmall cell lung cancer. * Describe the toxicity of Durvalumab when initiated quickly after chemoradiation for unresectable Stage II or Stage III nonsmall cell lung cancer as compared to historical controls. * Describe the efficacy of Durvalumab when initiated quickly after chemoradiation for unresectable Stage II or Stage III nonsmall cell lung cancer as compared to historical controls.

Interventions

• Drug Durvalumab
  Participants will receive Durvalumab 1500 mg intravenously every two weeks for 60 minutes. Each treatment is called a cycle and lasts for four weeks (or 28 days).
• Other the EORTC Core Quality of Life Questionnaire (EORTC QLQ-C30)
  Participants will be asked to answer all 30 items on the EORTC Core Quality of Life questionnaire (EORTC QLQ-C30). This patient-reported outcome measure is designed to measure cancer patients' physical, psychological and social functions. The measure can be completed using a paper form, by verbally providing answers to the study team, or by entering the answers online into REDCap using a computer or mobile device. The total time to complete the questionnaire is approximately 11 minutes (
• Diagnostic test COPD Assessment Test (CAT)
  Participants will be asked to answer all items on the COPD assessment test (8 items) and the patient-reported outcome measures designed to measure respiratory function. The measures can be completed using a paper form, by verbally providing answers to the study team, or by entering the answers online into REDCap using a computer or mobile device. The total time to complete the questionnaire is less than 5 minutes.
• Diagnostic test Modified Medical Research Council (mMRC) dyspnea scale
  Participants will be asked to answer the modified medical research council dyspnea scale (1 item), and the patient-reported outcome measures designed to measure respiratory function. The measures can be completed using a paper form, by verbally providing answers to the study team, or by entering the answers online into REDCap using a computer or mobile device. The total time to complete the questionnaire is less than 5 minutes.

Primary outcome measures

• Number of Participants to Achieve Fidelity to Early Treatment with Durvalumab - Early Initiation (1-14 days) [Time frame: 48 weeks]

Secondary outcome measures (10)

• Number of Participants to Achieve Fidelity to Early Treatment with Durvalumab - Very Early (1-7 days) [Time frame: Up to 13 months]
• Number of Barriers to Initiation of Durvalumab - Very Early (Days 1-7) [Time frame: Up to 13 months]
• Number of Barriers to Initiation of Durvalumab - Early (Days 8-14) [Time frame: Up to 13 months]
• Number of Participants with All Adverse Events [Time frame: Within 85 days of intervention (Cycles 1-3)]
• Number of Participants Who Have Immune-Mediated Pneumonitis [Time frame: Within 85 days of intervention (Cycles 1-3)]
• Number of Participants Who Have All-Cause Any Grade Pneumonitis [Time frame: Within 85 days of intervention (Cycles 1-3)]
• Number of Participants to Discontinue Durvalumab Due to Adverse Events [Time frame: One year]
• Overall Survival [Time frame: One year]
• Progression-Free Survival [Time frame: One year]
• Response Rate [Time frame: One year]

Eligibility criteria

Inclusion criteria

• Patients must have stage II or stage III NSCLC confirmed by histologic or cytologic documentation and by clinical assessment. Staging is defined according to the AJCC Cancer Staging Manual, 8th Edition (2017).
• Unresectable or medically inoperable as determined by the investigator.
• The patient has definitive radiation therapy (e.g., 54 Gy to 66 Gy in 30 to 35 fractions) for lung cancer that is either (a) planned to start within the next 28 days, or (b) currently being administered, or (c) has been completed within the last 14 days.
• Platinum-based chemotherapy for lung cancer that is either (a) planned to start within the next 28 days, (b) currently being administered, or (c) has been completed within the last 14 days. Chemotherapy must be for at least two cycles and be administered either before radiation therapy ("induction" or "sequential") or during radiation therapy ("concurrent").
• Consolidation durvalumab is planned for NSCLC after radiation and chemotherapy.
• Eighteen years old or greater.
• ECOG performance status of 0-2.
• Life expectancy of greater than three months.
• Patients with sexual relationships in which either they or their partner may become pregnant must use contraception during the study treatment period.
• Ability to understand and be willing to sign an IRB-approved informed consent document directly or via a legally authorized representative.

Exclusion criteria

• Uncontrolled respiratory symptoms (i.e., cough, dyspnea, fevers, chest pain, or an increase from baseline oxygen requirements) that are interfering with activities of daily living.
• Nonsmall cell lung cancer is known to have a tumor with a mutation in EGFR associated with sensitivity to first-line therapy with a tyrosine kinase inhibitor (i.e., Ex19del or L858R). Testing for EGFR mutation must have been attempted for study enrollment. If EGFR testing is inconclusive (e.g., the biopsy's quantity or quality is not sufficient for testing to be performed) and there is low clinical suspicion for the presence of an EGFR mutation as determined by the investigator, then the patient is eligible.
• Prior exposure to an immune checkpoint inhibitor targeting CTLA-4, PD-1, or PD-L1.
• Active autoimmune disease requiring systemic immunosuppression at the time of enrollment.
• History of autoimmune pneumonitis requiring high-dose systemic steroids (equivalent prednisone >20 mg/day for more than one week).
• Uncontrolled intercurrent illness includes ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patients who are pregnant or breastfeeding.

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

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Wake Forest Baptist Comprehensive Cancer Center — Winston-Salem

Identifiers

NCT: NCT05696782 · IRB00092850 · WFBCCC 62422 · P30CA012197

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗