Study of Low-Dose Radiotherapy Concurrent Cisplatin/Carboplatin Plus Etoposide With Serplulimab for Patients With ES-SCLC

Phase II, Single-Arm Study of Low-Dose Radiotherapy (LDRT) Concurrent Cisplatin/Carboplatin Plus Etoposide With Serplulimab for Patients With Extensive-Stage Small Cell Lung Cancer

This is a Phase II, single arm, multicenter study designed to evaluate the safety and efficacy of low-dose radiotherapy (LDRT) concurrent cisplatin/carboplatin plus etoposide with serplulimab in participants who have extensive-stage small cell lung cancer (ES-SCLC) and are chemotherapy-navïe for their extensive-stage disease.

Study Overview

• Status: Recruiting
• Conditions: Extensive-stage Small-cell Lung Cancer
• Intervention / Treatment: Drug: Carboplatin; Drug: Etoposide; Drug: serplulimab; Drug: Cisplatin; Radiation: Thoracic radiation therapy (TRT)

• Study Type: Interventional
• Enrollment (Estimated): 61
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zhuoran Yao, MD; Phone Number: 13261660839; Email: yaozhuoran@outlook.com
• Study Contact Backup: Name: Li Li, BA; Phone Number: 02885424619; Email: tracy.li_2010@hotmail.com

Study Locations

• China
  • GuangGong
    • Guangzhou, GuangGong, China, 510405
      • Recruiting
      • The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine
      • Contact: LIzhu Lin
  • Guangdong
    • Shantou, Guangdong, China, 515041
      • Recruiting
      • Cancer Hospital of Shantou University Medical College
      • Contact: Zhixiong Lin
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Recruiting
      • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
      • Contact: Sheng Zhang
  • Liaoning
    • Shenyang, Liaoning, China, 110801
      • Recruiting
      • Liaoning cancer Hospital & Institute
      • Contact: Deyu Sun
  • Shandong
    • Jinan, Shandong, China, 250021
      • Recruiting
      • Shandong Provincial Hospital
      • Contact: Zhe Yang
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Recruiting
      • Fudan University Shanghai Cancer Center
      • Contact: Weixin Zhao
  • Sichuan
    • Chengdu, Sichuan, China, 610000
      • Recruiting
      • China West Hospital
      • Contact: Zhuoran Yao, MD; Phone Number: 13261660839; Email: yaozhuoran@outlook.com
      • Contact: You Lu, MD; Phone Number: 00862885423571; Email: radyoulu@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Main Inclusion Criteria:

1. Histologically or cytologically confirmed ES-SCLC
2. No prior treatment for ES-SCLC
3. Measurable disease, as defined by RECIST v1.1. Previously irradiated lesions can be considered as measurable disease only if progressive disease has been unequivocally documented at that site since radiation.
4. ECOG performance status of 0 or 1
5. Life expectancy >= 3 months
6. Adequate hematologic and end-organ function
7. For participants receiving therapeutic anticoagulation: stable anticoagulant regimen
8. Negative human immunodeficiency virus (HIV) test at screening
9. Negative hepatitis B surface antigen (HBsAg) test at screening
10. Positive hepatitis B surface antibody (HBsAb) test at screening, or negative HBsAb at screening accompanied by either of the following: Negative total hepatitis B core antibody (HBcAb), or positive total HBcAb test followed by a negative hepatitis B virus (HBV) DNA test. The HBV DNA test will be performed only for participants who have a negative HBsAg test, a negative HBsAb test, and a positive total HBcAb test.
11. Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening. The HCV RNA test will be performed only for participants who have a positive HCV antibody test.
12. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception
13. For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm

Main Exclusion Criteria:

1. Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
2. Participants with pulmonary artery invasion
3. History of leptomeningeal disease
4. Uncontrolled tumor-related pain
5. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
6. Uncontrolled or symptomatic hypercalcemia
7. Active or history of autoimmune disease or immune deficiency
8. History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
9. Active tuberculosis
10. Significant cardiovascular disease within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
11. History of malignancy other than small cell lung cancer (SCLC) within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: LDRT concurrent cisplatin/carboplatin + etoposide + serplulimab; Participants will receive the following treatment regimens: LDRT concurrent cisplatin/carboplatin + etoposide + serplulimab. Induction treatment will be administered on a 21-day cycle for four cycles. Concurrent radiation therapy will be conducted from Day 1 - Day 5 in the first cycle. Following the induction phase, participants will continue maintenance therapy with serplulimab and thoracic radiation therapy (30Gay/10f）. Participants will be treated until loss of clinical benefit, or unaccepted toxicity, or withdrawal of consent, or death (whichever occurs first).

Drug: Carboplatin; Carboplatin will be administered as intravenous infusion at a dose of area under the concentration-time curve (AUC) of 5 mg/mL/min on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4).; Drug: Etoposide; Etoposide will be administered intravenously at a dose of 100 mg/m^2 on Days 1, 2 and 3 of each 21-day cycle during the induction phase (Cycles 1-4).; Drug: serplulimab; Serplulimab will be administered by intravenous infusion at a dose of 4.5mg/kg on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, and clinical status.; Drug: Cisplatin; Cisplatin will be administered as intravenous infusion at a dose of 75 mg per meter squared (75 mg/m^2) after completion of serplulimab on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4).; Radiation: Thoracic radiation therapy (TRT); Participants will receive concurrent thoracic radiation therapy (TRT) treatment, in once daily fractions, 3 Gy per fraction, to a target dose of 15 Gy in 5 fractions from Day 1-Day 5 in the first cycle.Following the induction phase, participants will continue maintenance therapy with serplulimab thoracic radiation therapy (TRT) treatment, in once daily fractions, 3 Gy per fraction, to a target dose of 30 Gy in 10 fractions in the fifth and sixth cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	The time from the date of first dosing of durvalumab to the first appearance of objective disease progression (according to RECIST1.1) or death from any cause (if it occurs before disease progression).	Baseline up to approximately 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS Rate at 6 Months and 1 Year	PFS rate at 6 months and 1 year, defined as the proportion of patients who have not experienced disease progression or death from any cause at 6 months and 1 year separately, as determined by the investigator according to RECIST v1.1.	Baseline up to 1 year
OS Rate at 1 Year and 2 Years	OS rate at 1 year and 2 years, defined as the proportion of patients who have not experienced death from any cause at 1 year and 2 years.	Baseline to 2 years or death, whichever occurs first.
Percentage of Participants With Adverse Event		Baseline up to approximately 36 months
Overall Survival (OS)	OS, defined as the time from initiation of study treatment to death from any cause.	Baseline up to approximately 24 months
Duration of response (DOR)	defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1.	Baseline to disease progression or death from any cause (whichever occurs first)(up to approximately 24 months)
Disease control rate (DCR)	defined as the proportion of participants who have a best overall response of CR or PR or stable disease (SD), as determined by the investigator according to RECIST v1.1.	Baseline up to approximately 24 months

Collaborators and Investigators

• Sponsor: Sichuan University
• Investigators: Study Chair: You Lu, MD, West China Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 7, 2023
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: March 1, 2023
• First Submitted That Met QC Criteria: March 1, 2023
• First Posted (Actual): March 13, 2023

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Carboplatin; Etoposide
• Other Study ID Numbers: ASTRUM-LC04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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