Nonsmall Cell Lung Cancer Stage III, Unresectable Non-Small Cell Lung Carcinoma, Nonsmall Cell Lung Cancer, Stage II
Conditions
Brief summary
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
DRUGDurvalumab
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).
OTHERthe 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_TESTCOPD 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_TESTModified 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.
Sponsors
Wake Forest University Health Sciences
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants to Achieve Fidelity to Early Treatment with Durvalumab - Early Initiation (1-14 days) | 48 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants to Achieve Fidelity to Early Treatment with Durvalumab - Very Early (1-7 days) | Up to 13 months | 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. |
| Number of Barriers to Initiation of Durvalumab - Very Early (Days 1-7) | Up to 13 months | 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. |
| Number of Barriers to Initiation of Durvalumab - Early (Days 8-14) | Up to 13 months | 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. |
| Number of Participants with All Adverse Events | Within 85 days of intervention (Cycles 1-3) | 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. |
| Number of Participants Who Have Immune-Mediated Pneumonitis | Within 85 days of intervention (Cycles 1-3) | 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 \[1-3 cycles\]). |
| Number of Participants Who Have All-Cause Any Grade Pneumonitis | Within 85 days of intervention (Cycles 1-3) | Participants with all-cause any-grade pneumonitis and early onset. |
| Number of Participants to Discontinue Durvalumab Due to Adverse Events | One year | Participants who discontinue Durvalumab at any point due to an adverse event of any cause. |
| Overall Survival | One year | 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. |
| Progression-Free Survival | One year | 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. |
| Response Rate | One year | 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. |
Countries
United States
Contacts
CONTACTStudy Coordinator
PRINCIPAL_INVESTIGATORThomas Lycan, MD
Wake Forest Baptist Comprehensive Cancer Center
Outcome results
None listed