Sequential Chemo-immunotherapy Plus Thoracic Radiotherapy for Elderly and/or Frail Stage III Non-small-cell Lung Cancer

Study Overview
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Brief Summary
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Concurrent chemoradiotherapy without disease progression followed by consolidation durvalumab is standard of care for unresectable, stage III non-small-cell lung cancer (NSCLC) (the 'PACIFIC regimen'). However, many patients with poor performance status, older age or comorbidities may be ineligible for chemotherapy due to expected high toxicity. The present study aim to investigate the efficacy and toxicities of sequential chemo-immunotherapy plus thoracic radiotherapy for elderly and/or frail stage III NSCLC patients unfit for concurrent chemoradiotherapy, and to identify the optimal thoracic dose for this patient population.

Official Title
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Sequential Chemo-immunotherapy Plus Thoracic Radiotherapy for Elderly and/or Frail Stage III Non-small-cell Lung Cancer Patients Unfit for Concurrent Chemoradiotherapy: an Open Label, Two Cohorts, Prospective Trial

Conditions
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Non-small Cell Lung Cancer Stage III

Intervention / Treatment
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* Radiation: standar thoracic RT dose
* Radiation: decreased thoracic RT dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years at time of study entry Histologically documented diagnosis of unresectable stage III NSCLC; Fully-informed written consent obtained from patients; Unfit for concurrent chemoradiotherapy as determined by the multi-disciplinary team board due to one of the following reasons: (1) ECOG 2; (2)age≥70;(3) ECOG 1 and CCI≥1； Adequate bone marrow, liver and kidney function Life expectancy of at least 3 months At least one measurable (RECIST 1.1), thoracic lesion that can be irradiated Histologic or cytologic confirmation of small cell lung cancer Adequate pulmonary function with FEV1 >1 L or >30 % of predicted value and DLCO >30 % of predicted value Exclusion Criteria: Previous chemo-, immuno- or radiotherapy for NSCLC Major surgical procedure last 28 days History of allogenic organ transplantation, autoimmune disease, immunodeficiency, hepatitis or HIV Uncontrolled intercurrent illness Other active malignancy Leptomeningeal carcinomatosis Immunosuppressive medication Pregnant or breastfeeding women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: standar thoracic RT dose<br>Sequential chemo-immunotherapy plus standard dose of thoracic radiotherapy followed by anti-PD-1/PD-L1 maintenance therapy | Radiation: standar thoracic RT dose<br>* All the enrolled patients will be patients with NSCLC who did not have PD (determined as per the RECIST v1.1) after 4 cycle of platinum-based chemotherapy in combination with an anti-PD-1/L1. Then, those enrolled patients would be treated with standard dose thoracic radiotherapy of 60 Gy/30Fx concurrently with PD-1/PD-L1 maintenance therapy, and the total maintenance therapy time should at least more than 6 months.<br>|
| Experimental: decreased thoracic RT dose<br>Sequential chemo-immunotherapy plus decreased thoracic radiotherapy followed by anti-PD-1/PD-L1 maintenance therapy | Radiation: decreased thoracic RT dose<br>* All the enrolled patients will be patients with NSCLC who did not have PD (determined as per the RECIST v1.1) after 4 cycle of platinum-based chemotherapy in combination with an anti-PD-1/L1. Then, those enrolled patients would be treated with decreased thoracic radiotherapy of 50Gy/25Fx concurrently with PD-1/PD-L1 maintenance therapy, and the total maintenance therapy time should at least more than 6 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression-free survival | time from treatment start until death or progression of tumor disease within one year | 12 months after last patient entry | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1-year overall survial | time from treatment start until death with in one year | 12 months after last patient entry | 
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 within one year | Safety and Tolerability | 12 months after last patient entry | 
| 5-year overall survival | Time from treatment start until death | 5-years after last patient entry | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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thoradic radiotherapy, non-small-cell lung cancer, chemo-immunotherapy, survival