Nonsmall Cell Lung Cancer Stage III Clinical Trial
Official title:
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.
| Status | Recruiting |
| Enrollment | 28 |
| Est. completion date | July 2026 |
| Est. primary completion date | May 2025 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | Inclusion Criteria: - Patients must have Stage III nonsmall cell lung cancer confirmed by histologic or cytologic documentation and by clinical assessment. Stage III nonsmall cell lung cancer is defined according to the American Joint Committee on Cancer Staging Manual, 8th Edition (2017). - Unresectable or medically inoperable as determined by the investigator. - The participant 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 nonsmall cell lung cancer 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 progressed during radiation therapy. - 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, L858R, EGFR S768I, L861Q, or G719X). If not already known, testing for EGFR mutations is not required for study enrollment. - 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. |
| Country | Name | City | State |
|---|---|---|---|
| United States | Wake Forest Baptist Comprehensive Cancer Center | Winston-Salem | North Carolina |
| Lead Sponsor | Collaborator |
|---|---|
| Wake Forest University Health Sciences |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | 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 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 12 weeks after start of intervention | |
| Other | 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 12 weeks after start of intervention | |
| Other | 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 12 weeks after start of intervention | |
| Other | 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 12 weeks after start of intervention | |
| Primary | 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) 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 | 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 | |
| Secondary | Number of Barriers to Initiation of Durvalumab - Very Early (Days 1-7) | 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 | |
| Secondary | Number of Barriers to Initiation of Durvalumab - Early (Days 8-14) | 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 | |
| Secondary | Incidences of All Adverse Events | Adverse events, serious adverse events and immune-related adverse events will be tabulated by fidelity status (1-7 days vs. 8-14 days vs. neither) using National Cancer Institute Common Terminology Criteria, version 5.0. | Up to 13 months after intervention | |
| Secondary | Number of Participants Who Have Immune-Mediated Pneumonitis - Early Fidelity (1-14 days) | Participants with early (1-14 days) fidelity who have immune-mediated early-onset pneumonitis will be estimated and statistically compared in a one-sample test of proportions. | Within 85 days of intervention (Cycles 1-3) | |
| Secondary | Number of Participants Who Have All-Cause Pneumonitis - Early Fidelity (1-14 days) | Participants with all-cause early-onset pneumonitis among those with early (1-14 days) fidelity and statistically compare it, using a one-sample test of proportions. | Within 85 days of intervention (Cycles 1-3) | |
| Secondary | Number of Participants to Discontinue Durvalumab Due to Adverse Events | Participants with early fidelity who discontinue Durvalumab at any point due to an adverse event of any cause and compare it using a one-sample test of proportions. | One year | |
| Secondary | 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 | |
| Secondary | 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 | |
| Secondary | 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 |
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