Phase 2a Clinical Trial to Evaluate the Efficacy and Safety of HL301 on Radiation Pneumonitis in Non-small Cell Lung Cancer Patients

Study Overview
=================
Brief Summary
-----------------
The purpose of this clinical trial is to evaluate the safety when HL301 is administered to unresectable non-small cell lung cancer patients who receive chemoradiotherapy with Paclitaxel and Carboplatin and to search for a clinically appropriate dose by evaluating the efficacy by comparing the radiation pneumonia incidence rate with the control group.

Official Title
-----------------
A Multicenter, Randomized, Double-blinded, Placebo-controlled, Phase 2a Clinical Trial to Evaluate the Efficacy and Safety of HL301 Versus Placebo on Radiation Pneumonitis in Unresectable Non-small Cell Lung Cancer Patients Treated With Curative Concurrent Chemoradiotherapy Using Paclitaxel and Carboplatin

Conditions
-----------------
Radiation Pneumonitis, Lung Cancer

Intervention / Treatment
-----------------
* Drug: HL301 tablet 300mg
* Drug: Placebo of HL301 tablet


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or Female, age ≥ 19 years Stage III non-small cell lung cancer(NSCLC) patient who without surgical treatment Patients scheduled for curative concurrent chemoradiotherapy chemotherapy : paclitaxel and carboplatin radiation therapy : IMRT, total 60 70Gy Eastern Cooperative Oncology Group(ECOG) performance status of 0 to 2 at the screening visit Subject whose remaining life expectancy is more than 6 months according to the judgment of investigator Volunteer, be willing and able to provide written informed consent for the trial Exclusion Criteria: Subjects with pleural effusion Subjects with a weight loss of 10% or more within the last 6 months from the screening visit Subjects with a history of thoracic or neck radiotherapy or chemotherapy prior to screening visit Subjects with distant metastases Subjects with liver/renal dysfunction according to the following criteria on the screening test Total Bilirubin >1.5 mg/dL ALT or AST level is 2.0 times higher than the upper limit of normal (based on the institution) Serum Creatinine >1.5 mg/dL Subjects with serious cardiovascular disease within 3 months prior to the screening visit (ex. arrhythmia, congestive heart failure, infarction, unstable angina etc) Subjects with serious systemic infection (≥ Grade 3, evaluated by CTCAE v5.0) Patients with chronic or interstitial lung disease (excluding patients with chronic obstructive pulmonary disease (COPD)), patients with chronic bronchitis, patients with pneumonia Subjects with thyroid dysfunction as present illness at the screening visit Subjects who administered systemic steroids within 4 weeks prior to the date of randomization (except for cases when administered to prevent hypersensitivity reaction of paclitaxel) Subjects who are hypersensitive to investigational products and standard anticancer treatments Subjects who participate in other clinical trials within 30 days prior to the screening visit and administer investigational drugs or apply clinical trial medical devices Women of childbearing age or men who do not agree to use a medically accepted method of contraception during the clinical trial Pregnant or breast-feeding Subjects who have clinical significance that is considered inappropriate for this clinical trial as judged by the investigator

Ages Eligible for Study
-----------------
Minimum Age: 19 Years

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

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

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

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental group 1<br>HL301 1,200mg/day | Drug: HL301 tablet 300mg<br>* Experimental group 1 : 2 tablets at once, twice a day Experimental group 2 : 2 tablets at once, three times a day<br>|
| Experimental: Experimental group 2<br>HL301 1,800mg/day | Drug: HL301 tablet 300mg<br>* Experimental group 1 : 2 tablets at once, twice a day Experimental group 2 : 2 tablets at once, three times a day<br>|
| Placebo Comparator: Control group<br>Placebo | Drug: Placebo of HL301 tablet<br>* 2 tablets at once, three times a day<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of subjects with radiation pneumonia of ≥ Grade 2 | Percentage of subjects with radiation pneumonia of ≥ Grade 2 evaluated by CTCAE v5.0 | up to 24 weeks after completion of radiotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of radiation pneumonia | The incidence of radiation pneumonia | p to 24 weeks after completion of radiotherapy | 
| Percentage of subjects with radiation pneumonia of ≥ Grade 3 | Percentage of subjects with radiation pneumonia of ≥ Grade 3 evaluated by CTCAE v5.0 | up to 24 weeks after completion of radiotherapy | 
| Severity at the first diagnosis of radiation pneumonia | Severity at the first diagnosis of radiation pneumonia evaluated by CTCAE v5.0 | up to 24 weeks after completion of radiotherapy | 
| Maximum severity of radiation pneumonia | Maximum severity of radiation pneumonia evaluated by CTCAE v5.0 | up to 24 weeks after completion of radiotherapy | 
| Changes in lung function | Changes in lung function (FEV1, DL CO) at each time point after administration compared to before administration of investigational products | at 4 weeks and 12 weeks after completion of radiotherapy | 
| The incidence of pulmonary fibrosis | The incidence of pulmonary fibrosis | at 24 weeks after completion of radiotherapy | 
| Lung fibrosis area | Lung fibrosis area | at 24 weeks after completion of radiotherapy | 
| Lung volume reduction | Lung volume reduction | at 24 weeks after completion of radiotherapy | 
| Pulmonary toxicity grade | Pulmonary toxicity grade evaluated by Radiation Therapy Oncology Group (RTOG) Acute radiation morbidity | at the time of initial diagnosis of radiation pneumonia after completion of radiotherapy | 
| The maximum grade of lung toxicity | The maximum grade of lung toxicity evaluated by RTOG Acute radiation morbidity | up to 24 weeks after completion of radiotherapy |