Radiotherapy Combined With Thymosin for Metastatic NSCLC Patients Who Showed Stable Disease After First Line TKI Therapy

Study Overview
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Brief Summary
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The investigators postulated that the exploitation of the pro-immunogenic effects of radiotherapy with thymosin might result in abscopal responses among patients with metastatic cancer. The research is designed to evaluate the efficacy and toxicity of patients treated with hypofractionated radiotherapy combined with thymosin alpha 1. An exploratory biomarker analysis in blood and tumor samples is also planned.

Official Title
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A Phase II Trial of Hypofractionated Radiotherapy Combined With Thymosin for Metastatic NSCLC Patients Who Showed Stable Disease After First Line TKI Therapy

Conditions
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Lung Adenocarcinoma

Intervention / Treatment
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* Drug: TKI
* Radiation: Thoracic Hypofractionated Radiotherapy
* Drug: Thymosin Alpha 1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newly diagnosed metastatic lung adenocarcinoma harboring sensitizing EGFR mutations (L858R, exon 19 deletion), and showed stable disease after 3 months TKI, evaluated twice by PET/CT scan, brain MRI, and abdomen ultrasound (≥3 measurable lesions, and these lesions haven't received local therapy) Age 18 years or older ECOG Performance Status 0-2 Adequate bone marrow, liver and renal function, as specified below: Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L; Hemoglobin ≥ 8 g/dL; Platelets ≥ 100 x 109/L; Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN) ; AST and ALT ≤ 2.5 x ULN or ≤ 5 x ULN if liver metastases are present; Serum creatinine ≤ 1.5 x upper limit of normal or creatinine clearance ≥ 60ml/min for patients with creatinine levels above institutional normal For women of child-bearing potential, negative pregnancy test within 14 days prior to starting treatment Men and women of childbearing age must be willing to use effective contraception while on treatment and for at least 3 months thereafter Patients and their family signed the informed consents Exclusion Criteria: Received chemotherapy before TKI therapy Brain parenchyma or leptomeningeal disease Concurrent malignancies other than non-melanoma skin cancer that require active ongoing treatment Any medical co-morbidities that would preclude radiation therapy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>After 3 mos TKI, patients showed stable disease take TKI, radiotherapy and thymosin alpha 1 till tumor progression. | Drug: TKI<br>* Gefitinib 250mg po qd or Erlotinib 150mg po qd or Icotinib 125mg po tid<br>* Other names: Gefitinib/Erlotinib/Icotinib;Radiation: Thoracic Hypofractionated Radiotherapy<br>* 40-45 Gy/5-15f<br>Drug: Thymosin Alpha 1<br>* Initiating thymosin alpha 1 therapy(1.6mg, qd, d1-d14;1.6mg, biw, d15-d90) at the second week of radiotherapy.<br>* Other names: Zadaxin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of patients with an abscopal response assessed at 1-6 months after the radiation therapy | To assess the proportion of patients with an abscopal response (defined as at least a 30% decrease in the longest diameter of the best responding abscopal lesion) at 1-6 months after the radiation therapy | 1-6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the short-term quality of life (QOL) | FACT-E score at the 4 months after docetaxel consolidation therapy | 4 months | 
| Rate of CTCAE grade 2 or higher radiation pneumonitis | The investigators will assess the rate of symptomatic radiation pneumonitis in patients who received the radiation therapy | 1 years | 
| Overall Survival |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypofractionated Radiotherapy, Thymosin Alpha 1, Lung Adenocarcinoma, Tyrosine Kinase Inhibitors