Observational Prospective Study of Quality of Life in Unresectable TNM Stage III NSCLC (OBSTINATE)

Study Overview
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Brief Summary
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OBSTINATE is an observational, national, prospective, multicentric study on Quality of life in patients with unresecable stade III non-small cell lung cancers. Locally advanced non-small cell lung cancers (NSCLCs with a Tumor, Node and Metastasis [TNM] stage III) patients represent approximately a third of newly discovered NSCLCs every year, and a very heterogeneous group of clinical situations. Therapies are multidisciplinary and very heterogeneous across oncology centers. Patients with locally advanced NSCLC have a high symptom burden that is known to affect their quality of life. Health-related quality of life (HR-QoL) is a specific and multidimensional type of patient-reported outcome (PRO) related to the physical, psychological and social impact of the disease and its treatment as perceived by patients. HR-QoL allows, together with data of efficacy and safety, a more complete assessment of risks and benefits of each treatment. Therefore, QoL maintenance is a valuable consideration for treatment decisions, especially in the rapidly evolving therapeutic landscape of unresectable NSCLC. The study is designed to collect PROs HR-QoL data from every new patient diagnosed with an unresectable stage III NSCLC over a period of 18 months. We also aim to describe clinical characteristics of these patients, the therapeutic strategies conducted, and outcomes in a real-word oncological practice.

Detailed Description
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OBSTINATE is an observational, prospective, national, multicentric study conducted in patients newly diagnosed with an unresectable stage III NSCLC (with exclusion of early stages NSCLC classified to pathological stage III). OBSTINATE is a study planned to include 450 patients between 50 to 70 GFPC-affiliates or GFPC-associated centers approximately. All centers are located in France. The participating Site Investigators will be treating physicians within one of the participating centers. After screening for eligibility checks, patients will receive the Patient Information Note from the Site Investigators. This Patient information Note will describe the study purpose and modalities. Patients who meet the eligibility criteria and do not oppose to data collection will be enrolled. The schedule of the medical visits in the study center will depend on the patient and his/her routine clinical care Protocol-relevant data will be collected by the treating physician within each center, for up to 5 years following the last patient's enrollment in the study. Patients included in the study will complete the self-assess questionnaires at enrollment and during routine care follow-up, according to pre-specified data collection schedule. Usual practices or modalities of follow-up of patients will remain unchanged compared to the current clinical practice as the study is designed to provide descriptive summary information.

Official Title
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Observational Prospective Study of Quality of Life in Unresectable TNM Stage III NSCLC (OBSTINATE)

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Other: Quality of Life Questionnaire-Core 30 (QLQ-C30)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathological confirmation of NSCLC obtained from a tumor cytology or biopsy Treatment-naïve unresectable TNM stage III NSCLC (according to the 8th TNM IASLC edition). Of note, unresectability could be due to either functional limitation or anatomical extension of the tumor. Patient willing and able to complete collection of data via self-assessment questionnaires Patient without any local or systemic anti-neoplastic treatment are eligible (palliative symptomatic radiotherapy is considered best supportive care) Patients participating in other interventional or non-interventional studies can be included. Exclusion Criteria: Early stage NSCLC initially treated locally (surgery or other) and classified as pathological TNM stage III (according to the 8th TNM IASLC edition) At the treating physician's discretion, patient not eligible physically or psychologically to be included in a clinical trial Inability to read and/or fill out self-assessment questionnaires Patient unable to express opposition to data collection

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cohort 1: cRT-CT+IO<br>Concomitant radio-chemotherapy and consolidation immunotherapy (cRT-CT+IO) | Other: Quality of Life Questionnaire-Core 30 (QLQ-C30)<br>* The HR-QoL evaluation is based on three self-assessment questionnaires distributed to the patients according to the pre-specified data collection schedule. Patients will also complete an additional questionnaire on socio-economic and occupational outcomes<br>* Other names: 5-level EuroQoL EQ5D (EQ5D-5L);|
| Cohort 2: sRT-CT+IO<br>Sequential radio-chemotherapy and consolidation immunotherapy (sRT-CT+IO) | Other: Quality of Life Questionnaire-Core 30 (QLQ-C30)<br>* The HR-QoL evaluation is based on three self-assessment questionnaires distributed to the patients according to the pre-specified data collection schedule. Patients will also complete an additional questionnaire on socio-economic and occupational outcomes<br>* Other names: 5-level EuroQoL EQ5D (EQ5D-5L);|
| Cohort 3: cRT-CT<br>Concomitant radio-chemotherapy (cRT-CT) | Other: Quality of Life Questionnaire-Core 30 (QLQ-C30)<br>* The HR-QoL evaluation is based on three self-assessment questionnaires distributed to the patients according to the pre-specified data collection schedule. Patients will also complete an additional questionnaire on socio-economic and occupational outcomes<br>* Other names: 5-level EuroQoL EQ5D (EQ5D-5L);|
| Cohort 4: sRT-CT<br>Sequential radio-chemotherapy (sRT-CT) | Other: Quality of Life Questionnaire-Core 30 (QLQ-C30)<br>* The HR-QoL evaluation is based on three self-assessment questionnaires distributed to the patients according to the pre-specified data collection schedule. Patients will also complete an additional questionnaire on socio-economic and occupational outcomes<br>* Other names: 5-level EuroQoL EQ5D (EQ5D-5L);|
| Cohort 5: CT<br>Chemotherapy only (CT) | Other: Quality of Life Questionnaire-Core 30 (QLQ-C30)<br>* The HR-QoL evaluation is based on three self-assessment questionnaires distributed to the patients according to the pre-specified data collection schedule. Patients will also complete an additional questionnaire on socio-economic and occupational outcomes<br>* Other names: 5-level EuroQoL EQ5D (EQ5D-5L);|
| Cohort 6: CT+IO<br>Chemotherapy plus immunotherapy (CT+IO) | Other: Quality of Life Questionnaire-Core 30 (QLQ-C30)<br>* The HR-QoL evaluation is based on three self-assessment questionnaires distributed to the patients according to the pre-specified data collection schedule. Patients will also complete an additional questionnaire on socio-economic and occupational outcomes<br>* Other names: 5-level EuroQoL EQ5D (EQ5D-5L);|
| Cohort 7: RT<br>Radiation therapy only (RT) | Other: Quality of Life Questionnaire-Core 30 (QLQ-C30)<br>* The HR-QoL evaluation is based on three self-assessment questionnaires distributed to the patients according to the pre-specified data collection schedule. Patients will also complete an additional questionnaire on socio-economic and occupational outcomes<br>* Other names: 5-level EuroQoL EQ5D (EQ5D-5L);|
| Cohort 8: IO<br>Immunotherapy only (IO) | Other: Quality of Life Questionnaire-Core 30 (QLQ-C30)<br>* The HR-QoL evaluation is based on three self-assessment questionnaires distributed to the patients according to the pre-specified data collection schedule. Patients will also complete an additional questionnaire on socio-economic and occupational outcomes<br>* Other names: 5-level EuroQoL EQ5D (EQ5D-5L);|
| Cohort 9: TT<br>Targeted therapy only (TT) | Other: Quality of Life Questionnaire-Core 30 (QLQ-C30)<br>* The HR-QoL evaluation is based on three self-assessment questionnaires distributed to the patients according to the pre-specified data collection schedule. Patients will also complete an additional questionnaire on socio-economic and occupational outcomes<br>* Other names: 5-level EuroQoL EQ5D (EQ5D-5L);|
| Cohort 10: BSC<br>Best supportive care only (BSC) | Other: Quality of Life Questionnaire-Core 30 (QLQ-C30)<br>* The HR-QoL evaluation is based on three self-assessment questionnaires distributed to the patients according to the pre-specified data collection schedule. Patients will also complete an additional questionnaire on socio-economic and occupational outcomes<br>* Other names: 5-level EuroQoL EQ5D (EQ5D-5L);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| QLQ-C30 (defined as the outcomes of a clinical intervention obtained by the patient) | Change in patient's QLQ-C30 during treatment and follow-up until confirmed progression, loss of follow-up or end of the study compared to Baseline in patients diagnosed with unresectable stage III NSCLC in a real-world oncological practice. This evaluation is based on self-assess questionnaire distributed to the patients according to pre-specified data collection schedule. The primary objective will be addressed in the cohort as a whole, and independently for every cohort of interest. | Up to 6,5 years (18 months of recruitment + 5 years). For Cohort 1 & 2, a follow-up post progression is planned | 
| QLQ-LC13 (defined as the outcomes of a clinical intervention obtained by the patient) | Change in patient's QLQ-LC13 during treatment and follow-up until confirmed progression, loss of follow-up or end of the study compared to Baseline in patients diagnosed with unresectable stage III NSCLC in a real-world oncological practice. This evaluation is based on self-assess questionnaire distributed to the patients according to pre-specified data collection schedule. The primary objective will be addressed in the cohort as a whole, and independently for every cohort of interest. | Up to 6,5 years (18 months of recruitment + 5 years). For Cohort 1 & 2, a follow-up post progression is planned | 
| EQ5D-5L (defined as the outcomes of a clinical intervention obtained by the patient) | Change in patient's EQ5D-5L during treatment and follow-up until confirmed progression, loss of follow-up or end of the study compared to Baseline in patients diagnosed with unresectable stage III NSCLC in a real-world oncological practice. This evaluation is based on self-assess questionnaire distributed to the patients according to pre-specified data collection schedule. The primary objective will be addressed in the cohort as a whole, and independently for every cohort of interest. | Up to 6,5 years (18 months of recruitment + 5 years). For Cohort 1 & 2, a follow-up post progression is planned | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline demographics | Stage III unresectable NSCLC patients characteristics: baseline patient demographics at stage III NSCLC diagnosis, clinical, pathological and molecular characteristics (e.g. age, race, comorbidities) | At Baseline | 
| Tumor characteristics as defined by TNM stage | Characterize the stage III unresectable NSCLC patients by TNM stage according to the 8th TNM IASLC edition | At Baseline | 
| Tumor characteristics as defined by PD-L1 expression status | Characterize the stage III unresectable NSCLC patients by PD-L1 expression status (tumor propensity score) | At Baseline | 
| Tumor characteristics as defined by mutational status of driver genes | Characterize the stage III unresectable NSCLC patients by mutational status of driver genes (e.g. epidermal growth factor receptor [EGFR]) anaplastic lymphoma kinase [ALK], reactive oxygen species 1 [ROS1], human epidermal growth factor receptor 2 [HER2], PI3KCA, BRAF, MET, rearranged during transfection [RET], neurotrophic receptor tyrosine kinase [NRTK]) | At Baseline | 
| Time from diagnosis to treatment |  | From date of diagnosis until the date of first documented treatment or start date of best supportive care through study completion, up to 5 year | 
| Modality of follow-up | Description of modality of follow-up (e.g. type of imagery used, frequency of medical visit) | From date of diagnosis until the date of first documented progression or or date of death from any cause, whichever came first, assessed up to 5 years maximum | 
| Median PFS | Time from date of first treatment administration until the date of first documented progression or date to death from any cause, whichever came first as evaluated by investigators. | From date of first treatment administration up to first documented disease progression and/or death from any cause, whichever came first, assessed up to 60 months | 
| Median time to progression | Time from date of first treatment administration until the date of first documented progression or date to death from any cause, whichever came first as evaluated by investigators. | From date of first treatment administration up to first documented disease progression and/or death from any cause, whichever came first, assessed up to 60 months | 
| Median OS (e.g. median PFS, median OS) | Time from date of first treatment administration until the date of first documented progression or date to death from any cause, whichever came first as evaluated by investigators. | From date of first treatment administration up to first documented disease progression and/or death from any cause, whichever came first, assessed up to 60 months | 
| Treatment characteristics | Describe the chemotherapy, radiation therapy and immunotherapy protocols used (e.g. dose, reduction, interruptions, duration) | From date of first treatment administration up to end of study, assessed up to 5 years maximum | 
| Best response of treatment |  | From date of first treatment administration up to end of study, assessed up to 5 years maximum | 
| Duration of response of treatment |  | From date of first treatment administration up to end of study, assessed up to 5 years maximum | 
| Toxicity of treatment | limited to Cohorts 1, 2, 3 and 4 (restricted to significant AEs, which include but are not limited to: serious AEs [SAEs], AEs that led to treatment discontinuation, or any AEs ≥ grade 3 judged clinically significant by the Site Investigator) | From date of first treatment administration up to end of study, assessed up to 5 years maximum | 
| Effective treatment compared to initial Multidisciplinary Tumor Board (MDTB) decision | Concordance between effective treatment compared to initial MDTB decision | From date of first treatment administration up to end of study, assessed up to 5 years maximum | 
| Type of progression (local, loco-regional, metastatic) |  | At date of first documented progression, assessed up to 5 years maximum | 
| Description of second line of treatment after disease progression | Treatment characteristics after disease progression including type of treatment (chemotherapy, radiotherapy, immunotherapy or Tyrosine-Kinase inhibitors), treatment duration, stop date of treatment and reason for end of treatment | From date of first documented progression up to end of study, assessed up to 5 years maximum | 
| Change in patients' socio-economic and occupational outcomes using unique self questionnaire | Change in patients' socio-economic and occupational outcomes during treatment and follow-up until confirmed progression (of note, for Cohorts 1 and 2, a follow-up post-progression is planned), loss of follow-up or end of the study using a dedicated self questionnaire on socio-economic and occupational outcomes | From Baseline, during treatment and follow-up until confirmed progression (of note, for Cohorts 1 and 2, a follow-up post-progression is planned), loss of follow-up or end of the study, assessed up to 5 years maximum | 
| Evaluate the cost-utility of the therapeutic strategy using Quality-Adjusted Life Years (QALYs) |  | From Baseline, during treatment and follow-up until confirmed progression (of note, for Cohorts 1 and 2, a follow-up post-progression is planned), loss of follow-up or end of the study, assessed up to 5 years maximum | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-Small-cell lung cancer, Unresectable, Advanced stage