Clinical trial NCT05765825: Study of Low-Dose Radiotherapy Concurrent Chemotherapy With Serplulimab for Patients With ES-SCLC
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Extensive-stage Small-cell Lung Cancer
Lead sponsor: Sichuan University
Sponsor class: OTHER
First posted: 2023-03-13
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: Baseline up to approximately 24 months
Secondary outcomes:
measure: PFS Rate at 6 Months and 1 Year
timeFrame: Baseline up to 1 year
measure: Overall Survival (OS)
timeFrame: Baseline up to approximately 24 months
measure: OS Rate at 1 Year and 2 Years
timeFrame: Baseline to 2 years or death, whichever occurs first.
measure: Duration of response (DOR)
timeFrame: Baseline to disease progression or death from any cause (whichever occurs first)(up to approximately 24 months)
measure: Disease control rate (DCR)
timeFrame: Baseline up to approximately 24 months
measure: Percentage of Participants With Adverse Event
timeFrame: Baseline up to approximately 36 months
Other outcomes:
Locations:
city: Chongqing
country: China
facility: Chongqing University cancer hospital
state: Chongqing
city: Shantou
country: China
facility: Cancer Hospital of Shantou University Medical College
state: Guangdong
city: Wuhan
country: China
facility: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Shenyang
country: China
facility: LiaoNing Cancer Hospital & Institute
state: Liaoning
city: Jinan
country: China
facility: Shandong Provincial Hospital
state: Shandong
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Chengdu
country: China
facility: China West Hospital
state: Sichuan
city: Guiyang
country: China
facility: GuiZhou Provincial People's Hospital
Study officials:
affiliation: West China Hospital
name: You Lu, MD
role: STUDY_CHAIR
References: