Study of Low-Dose Radiotherapy Concurrent Chemotherapy With Serplulimab for Patients With ES-SCLC

Extensive-stage Small-cell Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05765825
• Other study ID #: SPUR
• Status: Recruiting
• Phase: Phase 2
• Start date: March 7, 2023
• Est. completion date: December 2025

Study information

• Verified date: June 2024
• Source: Sichuan University
• Contact: Zhuoran Yao, MD
• Phone: 13261660839
• Email: yaozhuoran[@]outlook.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

Enrolled patients will receive the following treatment regimen: LDRT-concurrent cisplatin/carboplatin plus etoposide in combination with serplulimab. The induction period consists of 4 cycles of 21 days each. Low-dose radiotherapy at 15Gy/5f will be performed concurrently from Day 1 to Day 5 (D1-D5) of Cycle 1. An efficacy assessment will be performed at the end of Cycle 2 and one week before the start of Cycle 3. For patients with primary lung lesions (intrathoracic lesions) evaluated as small PR (tumor shrinkage < 80%)/SD/PD, low-dose radiotherapy at 15Gy/5f will be performed in addition to serplulimab with chemotherapy in Cycle 3. For subjects evaluated as PD/SD/PR with extrathoracic residual metastases, low-dose radiotherapy at 15Gy/5f will be performed in addition to serplulimab with chemotherapy in Cycle 4. Definition of extrathoracic lesions for radiotherapy: Metastases to liver, metastases to adrenals and metastases to lymph nodes (at the discretion of the investigator).

After the induction period, the subjects will continue to receive maintenance treatment with serplulimab. Prophylactic cranial irradiation (PCI) is allowed for treatment according to local standard of care. Patients will be treated until loss of clinical benefit, unacceptable toxicity, withdrawal of informed consent, or death, whichever occurs first.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 61
• Est. completion date: December 2025
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Extensive-stage Small-cell Lung Cancer
• Lung Neoplasms
• Small Cell Lung Carcinoma

Intervention

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.
• 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).
• 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).
• 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).

Radiation:
• Thoracic radiation therapy (TRT)
Participants will receive concurrent low-dose radiotherapy 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, third cycle( For patients with primary lung lesions (intrathoracic lesions) evaluated as small PR (tumor shrinkage < 80%)/SD/PD),forth cycle(for subjects evaluated as PD/SD/PR with extrathoracic residual metastases).

Locations

Country	Name	City	State
China	China West Hospital	Chengdu	Sichuan
China	Chongqing University cancer hospital	Chongqing	Chongqing
China	GuiZhou Provincial People's Hospital	Guiyang
China	Shandong Provincial Hospital	Jinan	Shandong
China	Fudan University Shanghai Cancer Center	Shanghai	Shanghai
China	Cancer Hospital of Shantou University Medical College	Shantou	Guangdong
China	LiaoNing Cancer Hospital & Institute	Shenyang	Liaoning
China	Union Hospital, Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei

Sponsors (1)

Lead Sponsor	Collaborator
Sichuan University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival (PFS)	The time from the date of first dosing of serplulimab 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	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
Secondary	Overall Survival (OS)	The time from the date of first dosing of serplulimab to death from any cause.	Baseline up to approximately 24 months
Secondary	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.
Secondary	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)
Secondary	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
Secondary	Percentage of Participants With Adverse Event	• The incidence and severity of adverse events, with severity determined according to the U.S. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 5.0 (CTCAEv5.0)	Baseline up to approximately 36 months