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
Overview
- Phase
- Phase 2
- Intervention
- serplulimab
- Conditions
- Extensive-stage Small-cell Lung Cancer
- Sponsor
- Sichuan University
- Enrollment
- 61
- Locations
- 8
- Primary Endpoint
- Progression-free survival (PFS)
- Status
- Recruiting
- Last Updated
- last year
Overview
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.
Investigators
You Lu
professor
Sichuan University
Eligibility Criteria
Inclusion Criteria
- •Histologically or cytologically confirmed ES-SCLC
- •No prior treatment for ES-SCLC
- •Measurable disease, as defined by RECIST v1.
- •Previously irradiated lesions can be considered as measurable disease only if progressive disease has been unequivocally documented at that site since radiation.
- •ECOG performance status of 0 or 1
- •Life expectancy \>= 3 months
- •Adequate hematologic and end-organ function
- •For participants receiving therapeutic anticoagulation: stable anticoagulant regimen
- •Negative human immunodeficiency virus (HIV) test at screening
- •Negative hepatitis B surface antigen (HBsAg) test at screening
Exclusion Criteria
- •Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
- •Participants with pulmonary artery invasion
- •History of leptomeningeal disease
- •Uncontrolled tumor-related pain
- •Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
- •Uncontrolled or symptomatic hypercalcemia
- •Active or history of autoimmune disease or immune deficiency
- •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
- •Active tuberculosis
- •Significant cardiovascular disease within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
Arms & Interventions
LDRT concurrent cisplatin/carboplatin + etoposide + serplulimab
Participants will receive the following treatment regimens: The induction period consists of 4 cycles of 21 days each. Low-dose radiotherapy(LDRT) 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. For patients with primary lung lesions (intrathoracic lesions) evaluated as small PR (tumor shrinkage \< 80%)/SD/PD, ldrt 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, ldrt at 15Gy/5f will be performed in addition to serplulimab with chemotherapy in Cycle 4. After the induction period, the subjects will continue to receive maintenance treatment with serplulimab.
Intervention: serplulimab
LDRT concurrent cisplatin/carboplatin + etoposide + serplulimab
Participants will receive the following treatment regimens: The induction period consists of 4 cycles of 21 days each. Low-dose radiotherapy(LDRT) 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. For patients with primary lung lesions (intrathoracic lesions) evaluated as small PR (tumor shrinkage \< 80%)/SD/PD, ldrt 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, ldrt at 15Gy/5f will be performed in addition to serplulimab with chemotherapy in Cycle 4. After the induction period, the subjects will continue to receive maintenance treatment with serplulimab.
Intervention: Cisplatin
LDRT concurrent cisplatin/carboplatin + etoposide + serplulimab
Participants will receive the following treatment regimens: The induction period consists of 4 cycles of 21 days each. Low-dose radiotherapy(LDRT) 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. For patients with primary lung lesions (intrathoracic lesions) evaluated as small PR (tumor shrinkage \< 80%)/SD/PD, ldrt 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, ldrt at 15Gy/5f will be performed in addition to serplulimab with chemotherapy in Cycle 4. After the induction period, the subjects will continue to receive maintenance treatment with serplulimab.
Intervention: Carboplatin
LDRT concurrent cisplatin/carboplatin + etoposide + serplulimab
Participants will receive the following treatment regimens: The induction period consists of 4 cycles of 21 days each. Low-dose radiotherapy(LDRT) 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. For patients with primary lung lesions (intrathoracic lesions) evaluated as small PR (tumor shrinkage \< 80%)/SD/PD, ldrt 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, ldrt at 15Gy/5f will be performed in addition to serplulimab with chemotherapy in Cycle 4. After the induction period, the subjects will continue to receive maintenance treatment with serplulimab.
Intervention: Etoposide
LDRT concurrent cisplatin/carboplatin + etoposide + serplulimab
Participants will receive the following treatment regimens: The induction period consists of 4 cycles of 21 days each. Low-dose radiotherapy(LDRT) 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. For patients with primary lung lesions (intrathoracic lesions) evaluated as small PR (tumor shrinkage \< 80%)/SD/PD, ldrt 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, ldrt at 15Gy/5f will be performed in addition to serplulimab with chemotherapy in Cycle 4. After the induction period, the subjects will continue to receive maintenance treatment with serplulimab.
Intervention: Thoracic radiation therapy (TRT)
Outcomes
Primary Outcomes
Progression-free survival (PFS)
Time Frame: Baseline up to approximately 24 months
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).
Secondary Outcomes
- Disease control rate (DCR)(Baseline up to approximately 24 months)
- Overall Survival (OS)(Baseline up to approximately 24 months)
- OS Rate at 1 Year and 2 Years(Baseline to 2 years or death, whichever occurs first.)
- PFS Rate at 6 Months and 1 Year(Baseline up to 1 year)
- Duration of response (DOR)(Baseline to disease progression or death from any cause (whichever occurs first)(up to approximately 24 months))
- Percentage of Participants With Adverse Event(Baseline up to approximately 36 months)