Mobile Devices to Detect Early Pneumonitis in Stage III NSCLC Patients on Durvalumab.

Study Overview
=================
Brief Summary
-----------------
A study of whether mobile devices can improve the detection of pulmonary AEs (including pneumonitis) in stage III NSCLC patients post-CRT, while on durvalumab.

Detailed Description
-----------------
Patients undergoing post-CRT treatment for lung cancer with consolidation durvalumab can experience pulmonary AEs that could become severe if not recognized and treated in time. Data collected will be used to evaluate the likelihood of early detection of pulmonary AEs in unresectable Stage III NSCLC patients on durvalumab. This project seeks to understand if multiparametric mobile technology collecting patient reported outcomes, vital signs, and respiratory function, integrate well into a patients daily life and aid physicians in early detection of pulmonary AEs.

Official Title
-----------------
Prospective, Interventional Pilot Study of Mobile Devices and Digital Applications to Detect Early Pneumonitis and Other Pulmonary Adverse Events in Unresectable Stage III Non-Small Cell Lung Cancer Patients on Durvalumab

Conditions
-----------------
Unresectable Stage III NSCLC

Intervention / Treatment
-----------------
* Device: Multiparametric Mobile Technology


Participation Criteria
=================
Eligibility Criteria
-----------------
Select Inclusion Criteria: Patient has unresectable Stage III NSCLC that has not progressed following concurrent platinum-based chemotherapy and radiation therapy and is eligible to receive durvalumab according to the US FDA approved package insert. Patient is able and willing to use the mobile application and connected devices. Patient is able to complete QoL assessments. Select Exclusion Criteria: Patient is currently oxygen dependent. Patient has comorbidities that will prevent consistent and reliable measurement assessments with multiparametric mobile technology including severe chronic obstructive pulmonary disorder (COPD), severe asthma, congestive heart failure [CHF], interstitial lung disease [ILD], and others. Patients on other immunotherapy or systemic immunosuppressants. Patients with active or prior autoimmune disease or history of immunodeficiency. Currently pregnant women.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 130 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Observational/Other<br>Patients will be enrolled after their treating physician has prescribed durvalumab and before they start durvalumab treatment. Patients will receive mobile and wearable devices alongside their durvalumab treatment without any additional interventions. | Device: Multiparametric Mobile Technology<br>* Using a spirometer, an armband, and a tablet to collect data.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-Emergent Adverse Event (TEAE) of Pneumonitis by Grade | An AE was occurrence of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product or device, whether or not considered causally related to the product or device medical occurrence in a participant. The TEAEs of pneumonitis were defined as any pneumonitis event that occurred or worsened at any time after the start of administration of the first dose of durvalumab and through 30 days after the last dose of durvalumab. Severity (intensity of any event) was assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse events (CTCAE) v5. The AEs were assigned to a Grade from 1 through 5 as follows: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life-threatening requiring hospitalization; Grade 4: Life-threatening consequences; Grade 5: Death due to any AE. | TEAEs were reported from the first dose of durvalumab up to 30 days after the last dose of durvalumab, a maximum of approximately 13 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Permanent Discontinuation of Durvalumab Due to Pulmonary TEAEs | Pulmonary TEAEs were defined as any pulmonary AEs that occurred or worsened at any time after the start of administration of the first dose of durvalumab and through 30 days after the last dose of durvalumab. Number of participants with permanent discontinuation of durvalumab due to pulmonary TEAEs including pneumonitis are reported. | TEAEs were reported from the first dose of durvalumab up to 30 days after the last dose of durvalumab, a maximum of approximately 13 months | 
| Duration of Durvalumab Treatment | The overall duration of durvalumab treatment, while participants were a part of this wearable study, was calculated as end date of durvalumab treatment minus first dose of durvalumab (Day 1) plus 1. | Up to Month 12 | 
| Number of Participants With Early Discontinuation of Durvalumab | Number of participants who discontinued durvalumab early due to any reason are reported. | Up to Month 12 | 
| Number of Participants With Treatment Interruptions | Treatment interruptions were defined as at least 1 temporary withholding of durvalumab treatment. Treatment withheld was defined as temporarily withheld of durvalumab recorded in case report form. Short interruptions defined as the durvalumab infusion interruption during the administration recorded in CRF in a single visit were excluded from the analysis. Due to data issue, the reason for treatment withheld was not captured in the database. | Up to Month 12 | 
| Duration of Durvalumab Treatment Interruption | The overall duration of durvalumab treatment interruption was calculated as the sum of the duration of each treatment withheld/resumed. The duration of interruption included only treatment withheld. Short interruption which resumed during the same visit was not included in the calculation for duration of interruption. | Up to Month 12 | 
| Number of Participants With Pulmonary TEAEs Excluding Pneumonitis | Pulmonary TEAEs were defined as any pulmonary AEs that occurred or worsened at any time after the start of administration of the first dose of durvalumab and through 30 days after the last dose of durvalumab. | TEAEs were reported from the first dose of durvalumab up to 30 days after the last dose of durvalumab, a maximum of approximately 13 months | 
| Duration of Pulmonary TEAEs Excluding Pneumonitis | Pulmonary TEAEs were defined as any pulmonary AEs that occurred or worsened at any time after the start of administration of the first dose of durvalumab and through 30 days after the last dose of durvalumab. Duration of pulmonary TEAEs was calculated as end date of pulmonary TEAE minus onset date of pulmonary TEAE plus 1. For AEs that were missing an end date, the data cut-off date was used as the AE end date for calculation of AE duration. | TEAEs were reported from the first dose of durvalumab up to 30 days after the last dose of durvalumab, a maximum of approximately 13 months | 
| Number of Participants Who Received Prescription Medication to Manage Pneumonitis TEAEs | Pneumonitis TEAEs were defined as any pneumonitis AEs that occurred or worsened at any time after the start of administration of the first dose of durvalumab and through 30 days after the last dose of durvalumab. | Up to Month 12 | 
| Duration of Prescription Medication Received by Participants to Manage Pneumonitis TEAEs | Pneumonitis TEAEs were defined as any pneumonitis AEs that occurred or worsened at any time after the start of administration of the first dose of durvalumab and through 30 days after the last dose of durvalumab. | Up to Month 12 | 
| Duration of Development of Grade 3 to Grade 5 TEAEs, Including Pneumonitis | Duration of development of Grade 3 to 5 pneumonitis AEs is defined as the period from Day 1 to earliest of each grade of pneumonitis AE (grade 3, grade 4, and grade 5). Severity (intensity of an event) was assessed using the NCI-CTCAE v5. AEs were assigned to a Grade from 1 through 5 as follows: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life-threatening requiring hospitalization; Grade 4: Life-threatening consequences; Grade 5: Death due to any AE. | TEAEs were reported from the first dose of durvalumab up to 30 days after the last dose of durvalumab, a maximum of approximately 13 months | 
| Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) in Participants With Pneumonitis TEAEs | The EORTC QLQ-C30 consisted of 30 questions and included functional scales (FS) (items 1-7 and items 20-27), symptom scales (items 8-19 and item 28) and global measure of health status (GHS) (items 29-30). The scale ranged from 1-4 for most outcome measures of systems, with 1 rated as not at all and 4 rated as very much. Scores were averaged and transformed to 0 to 100, a high score for functional scales/GHS represented better functioning ability/QoL, whereas a high score for symptom scales represented stronger symptoms/worse QoL. Participants with pneumonitis TEAEs with causal relationship with durvalumab are presented. Time point 1: prior to occurrence of initial pneumonitis AE; Time point 2: at same time point as initial pneumonitis AE; Time point 3: when highest CTCAE grade of pneumonitis AE occurred. Baseline was defined as the date of informed consent for this parameter. | Baseline visit (Day 1), every 2 weeks for the first 3 months and once monthly thereafter, and at End-of-Study visit (Month 12) | 
| Change From Baseline in EORTC QLQ-Lung Cancer (LC)13 in Participants With Pneumonitis TEAEs | The EORTC QLQ-LC13 was a disease-specific 13-item questionnaire for lung cancer used in conjunction with the EORTC QLQ-C30. It comprised both multi-item and single-item measures of lung cancer associated symptoms (LCAS) (items 31-35 and items 40-42), treatment related side effects (TREF) (items 36-39) and pain medication (item 43). The scale ranged from 1-4 for most outcome measures of systems, 1 rated as not at all and 4 rated as very much. Scores were averaged and transformed to 0 to 100, higher scores for LCAS and TREF: greater level of symptoms/worse QoL and higher scores for pain medication: better pain relief from medication. Participants with pneumonitis TEAEs with causal relationship with durvalumab are presented. Time point 1: prior to occurrence of initial pneumonitis AE; Time point 2: at same time point as initial pneumonitis AE; Time point 3: when highest CTCAE grade of pneumonitis AE occurred. Baseline was defined as the date of informed consent for this parameter. | Baseline visit (Day 1), every 2 weeks for the first 3 months and once monthly thereafter, and at End-of-Study visit (Month 12) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
NSCLC, Non-Small Cell Lung Cancer, durvalumab, Stage III, Stage IIIA, Spirometer, Spirometry, PROs, Mobile Applications, Digital Applications, Stage IIIB, Stage IIIC, Device, Parametric, Pneumonitis