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

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

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.

Study Overview

• Status: Unknown
• Conditions: Lung Cancer; Radiation Pneumonitis
• Intervention / Treatment: Drug: HL301 tablet 300mg; Drug: Placebo of HL301 tablet

• Study Type: Interventional
• Enrollment (Anticipated): 87
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Yonsei University Health System, Severance Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Experimental group 1; HL301 1,200mg/day	Drug: HL301 tablet 300mg; Experimental group 1 : 2 tablets at once, twice a day; Experimental group 2 : 2 tablets at once, three times a day
EXPERIMENTAL: Experimental group 2; HL301 1,800mg/day	Drug: HL301 tablet 300mg; Experimental group 1 : 2 tablets at once, twice a day; Experimental group 2 : 2 tablets at once, three times a day
PLACEBO_COMPARATOR: Control group; Placebo	Drug: Placebo of HL301 tablet; 2 tablets at once, three times a day

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

Collaborators and Investigators

• Sponsor: Hanlim Pharm. Co., Ltd.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): November 1, 2020
• Primary Completion (ANTICIPATED): January 1, 2022
• Study Completion (ANTICIPATED): February 1, 2022

Study Registration Dates

• First Submitted: November 13, 2020
• First Submitted That Met QC Criteria: November 13, 2020
• First Posted (ACTUAL): November 17, 2020

Study Record Updates

• Last Update Posted (ACTUAL): November 17, 2020
• Last Update Submitted That Met QC Criteria: November 13, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Wounds and Injuries; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases, Interstitial; Lung Injury; Radiation Injuries; Lung Neoplasms; Pneumonia; Radiation Pneumonitis
• Other Study ID Numbers: HL_HL301_203

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No