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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Nonsmall Cell Lung Cancer Stage III; Unresectable Non-Small Cell Lung Carcinoma; Nonsmall Cell Lung Cancer, Stage II
• Intervention / Treatment: Drug: Durvalumab; Other: the EORTC Core Quality of Life Questionnaire (EORTC QLQ-C30); Diagnostic test: COPD Assessment Test (CAT); Diagnostic test: Modified Medical Research Council (mMRC) dyspnea scale

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.

• Study Type: Interventional
• Enrollment (Estimated): 28
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Study Coordinator; Phone Number: 336-713-0901; Email: Jada.Kluttz@wakehealth.edu

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Recruiting
      • Wake Forest Baptist Comprehensive Cancer Center
      • Contact: Study Nurse; Phone Number: 336-713-7748; Email: saverill@wakehealth.edu
      • Principal Investigator: Thomas Lycan, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Quick Start Durvalumab; Standard of care test and procedures for cancer treatments along with Durvalumab treatment at physician's discretion

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants to Achieve Fidelity to Early Treatment with Durvalumab - Early Initiation (1-14 days)	Fidelity is defined as a dichotomous composite indicator (yes/no) that describes whether the patient received very early (1-7 days) or early (days 8-14 days) initiation of Durvalumab as per protocol with all four of the following criteria having been met: (i) CT chest obtained after the last day of radiation therapy and before the first infusion of Durvalumab, (ii) first infusion within 14 days of completing radiation therapy, (iii) second and third doses received within 63 days of the first dose, and (iv) all infusions at least 28 days apart.	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants to Achieve Fidelity to Early Treatment with Durvalumab - Very Early (1-7 days)	Fidelity is defined as a dichotomous composite indicator (yes/no) that describes whether the patient received very early (1-7 days) initiation of Durvalumab as per protocol with all four of the following criteria having been met: (i) CT chest obtained after the last day of radiation therapy and before the first infusion of Durvalumab, (ii) first infusion within 7 days of completing radiation therapy, (iii) second and third doses received within 63 days of the first dose, and (iv) all infusions at least 28 days apart.	Up to 13 months
Overall Survival	Using Kaplan-Meier life table methods, overall survival is defined as the number of participants alive at 12 months after the first dose of Durvalumab.	One year
Progression-Free Survival	Using Kaplan-Meier methods, progression-free survival is defined as the number of participants alive and without disease progression as documented by the treating provider at 12 months after the first dose of Durvalumab.	One year
Response Rate	Best objective response rate (ORR) to Durvalumab is defined by either a complete response (CR) or partial response (PR) as per RECIST 1.1 criteria by investigator assessment and confirmed on at least two sequential imaging studies that are at least four weeks apart.; Complete Response (CR): Disappearance of all target lesions.; Partial Response (PR): Decrease by ≥ 30% in sum of longest diameter of target lesions.	One year
Number of Barriers to Initiation of Durvalumab - Very Early (Days 1-7)	Assess the barriers to the very early (1-7 days) initiation of durvalumab using a survey and free text reporting by study personnel and participants. Descriptive frequencies of participant survey answers will be examined to conduct qualitative analyses and determine appropriate categories of answers on the free text responses. We will examine barriers/obstacles for everyone in the sample, even those who achieve fidelity; such patients could have experienced delays even if they were still able to achieve fidelity. We will stratify answers/responses by fidelity status.	Up to 13 months
Number of Barriers to Initiation of Durvalumab - Early (Days 8-14)	Assess the barriers to the early (8-14 days) initiation of durvalumab using a survey and free text reporting by study personnel and participants. Descriptive frequencies of participant survey answers will be examined to conduct qualitative analyses and determine appropriate categories of answers on the free text responses. We will examine barriers/obstacles for everyone in the sample, even those who achieve fidelity; such patients could have experienced delays even if they were still able to achieve fidelity. We will stratify answers/responses by fidelity status.	Up to 13 months
Number of Participants with All Adverse Events	The number of participants with adverse events, serious adverse events, and immune-related adverse events (irAEs) within 85 days (i.e., 1-3 cycles) of the first infusion of durvalumab.	Within 85 days of intervention (Cycles 1-3)
Number of Participants Who Have Immune-Mediated Pneumonitis	The proportion of patients who have immune-mediated pneumonitis (i.e., excluding pneumonitis due to radiation), any grade, and early onset (i.e., within 85 days [1-3 cycles]).	Within 85 days of intervention (Cycles 1-3)
Number of Participants Who Have All-Cause Any Grade Pneumonitis	Participants with all-cause any-grade pneumonitis and early onset.	Within 85 days of intervention (Cycles 1-3)
Number of Participants to Discontinue Durvalumab Due to Adverse Events	Participants who discontinue Durvalumab at any point due to an adverse event of any cause.	One year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Patient-Reported Outcomes Scores (PROs) - European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Version 3	The change in PROs scores from baseline to cycle 4 using paired t-tests and compare mean difference scores to the null hypothesis value of zero change to compare between fidelity status (1-7 days vs. 8-14 days vs. neither). Scale scores range from 0 to 100. A high score for a functional scale represents a high level of functioning, whereas a high score for a symptom scale/single item represents a high level of symptomatology.	Baseline to cycle 4 (85 days) after start of intervention
Change in Patient-Reported Outcomes Scores (PROs) - Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13) Questionnaire	The QLQ-LC13 includes questions assessing lung cancer-associated symptoms (cough, hemoptysis, dyspnea and site specific pain), treatment-related side effects (sore mouth, dysphagia, peripheral neuropathy and alopecia) and pain medication. The change in PROs scores from baseline to week 12 using paired t-tests and compare mean difference scores to the null hypothesis value of zero change to compare between fidelity status (1-7 days vs. 8-14 days vs. neither). Scale scores range from 0 to 100. A high score for a functional scale represents a high level of functioning, whereas a high score for a symptom scale/single item represents a high level of symptomatology.	Baseline to cycles 4 (day 85), cycle 7 (day 169), cycle 10 (day 253) and cycle 13 (day 337) after start of intervention
Change in Respiratory Patient Reported Outcomes (PROs) - COPD Assessment Test (CAT)	The COPD Assessment Test (CAT) is a questionnaire for people with Chronic Obstructive Pulmonary Disease (COPD). It is designed to measure the impact of COPD on a person's life and how this changes over time. Range of CAT scores from 0-40. Higher scores denote a more severe impact of COPD. The change in PROs scores using paired t-tests and compare mean difference scores to the null hypothesis value of zero change to compare between fidelity status (1-7 days vs. 8-14 days vs. neither).	Baseline to cycles 4 (day 85), cycle 7 (day 169), cycle 10 (day 253) and cycle 13 (day 337) after start of intervention
Change in Respiratory Patient Reported Outcomes (PROs) - Modified Medical Research Council (mMRC) Dyspnea Scale	The mMRC (Modified Medical Research Council) Dyspnea Scale is used to assess the degree of baseline functional disability due to dyspnea.The mMRC breathlessness scale ranges from grade 0 to 4 with grade 4 indicating a higher level of respiratory disease severity.	Baseline to cycles 4 (day 85), cycle 7 (day 169), cycle 10 (day 253) and cycle 13 (day 337) after start of intervention
Changes in Sleep Scores - Sleep Questionnaires	We will examine risk of clinical sleep disorders and whether there is significant change in this score, using a paired sample t-test. The participant will be asked to answer all 7 items on the Insomnia Severity Index (ISI) and 10 items from the Berlin Sleep Questionnaire, a risk assessment for obstructive sleep apnea. The Insomnia Severity Index (ISI) is a 7-question tool (0-28 scale) that evaluates insomnia severity based on scores: 0-7 (no clinically significant insomnia), 8-14 (subthreshold), 15-21 (moderate clinical), and 22-28 (severe clinical). Scores of 15 or higher are generally considered clinically significant, often warranting further evaluation. The Berlin Questionnaire assesses the risk of obstructive sleep apnea (OSA) through three categories: snoring, sleepiness, and hypertension/obesity. High Risk if two or more categories are positive. Low risk only one or no categories are positive.	Baseline to cycles 4 (day 85), cycle 7 (day 169), cycle 10 (day 253) and cycle 13 (day 337) after start of intervention

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Thomas Lycan, MD, Wake Forest Baptist Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): July 26, 2023
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: January 12, 2023
• First Submitted That Met QC Criteria: January 12, 2023
• First Posted (Actual): January 25, 2023

Study Record Updates

• Last Update Posted (Actual): March 23, 2026
• Last Update Submitted That Met QC Criteria: March 18, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents, Immunological; Antineoplastic Agents; durvalumab
• Other Study ID Numbers: IRB00092850; P30CA012197 (U.S. NIH Grant/Contract); WFBCCC 62422 (Other Identifier: Wake Forest Baptist Comprehensive Cancer Center)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No