Trial Title:
Liposomal Irinotecan Combination Regimen for First-line Treatment of Small Cell Lung Cancer
NCT ID:
NCT06462105
Condition:
Small Cell Lung Cancer
Conditions: Official terms:
Lung Neoplasms
Small Cell Lung Carcinoma
Carboplatin
Irinotecan
Etoposide
Study type:
Interventional
Study phase:
N/A
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Irinotecan Hydrochloride Liposome Injection；Carboplatin Injection；Serplulimab Injection
Description:
Cohort 1: Liposomal irinotecan: 50mg/m2, ivgtt, d1; Carboplatin AUC=5, ivgtt, d1;
Serplulimab: 4.5mg/kg, ivgtt, d1; The drug was administered once every three weeks for a
total of 4 cycles. After 4 cycles, serplulimab is maintained until disease progression or
toxicity becomes intolerable.
Cohort 2: Etoposide: 100 mg/m2, ivgtt, d1-3; Carboplatin AUC=5, ivgtt, d1; Serplulimab:
4.5mg/kg, ivgtt, d1; The drug was administered once every three weeks for a total of 4
cycles. After 4 cycles, serplulimab is maintained until disease progression or toxicity
becomes intolerable.
Arm group label:
Etoposide + Carboplatin + Serplulimab
Arm group label:
Liposomal irinotecan + Carboplatin + Serplulimab
Other name:
Etoposide Injection；Carboplatin Injection；Serplulimab Injection
Summary:
Lung cancer is a malignant tumor with high incidence and mortality in China and the
world, among which small cell lung cancer (SCLC) accounts for 13% to 17% of lung cancer,
and about 250,000 patients are diagnosed with SCLC every year in the world, and nearly
200,000 people die from it. Due to the high degree of malignancy of SCLC, it is easy to
develop distant metastasis in the early stage, and most of the patients are diagnosed in
the late stage with poor prognosis. Although SCLC is sensitive to chemotherapy and
radiotherapy and has a high remission rate after initial treatment, it is prone to
secondary drug resistance and relapse. SCLC is a low-differentiated, high-grade
neuroendocrine tumor that can be classified into limited-stage and extensive stage
(ES-SCLC). Etoposide combined with cisplatin (EP regimen) or carboplatin (EC regimen),
irinotecan combined with cisplatin (IP regimen) or carboplatin (IC regimen) are the basis
of standard first-line therapy for ES-SCLC. Immunocombined chemotherapy has also become
the first-line standard treatment for ES-SCLC, among which serplulimab + etoposide +
carboplatin is recommended by CSCO guidelines for first-line treatment. Liposomal
irinotecan is irinotecan encapsulated by liposomes, which has advantages in safety. The
study is expected to achieve good efficacy, improve the quality of life and prolong the
survival of patients by combining the immune drug serplulimab on the basis of IC regimen.
After replacing ordinary irinotecan with liposomal irinotecan, this study aims to compare
the efficacy and safety of liposomal irinotecan + carboplatin + serplulimab with the
first-line standard regimen (etoposide + carboplatin + serplulimab) in patients with
extensive stage small-cell lung cancer, providing a better basis for clinical use.
Detailed description:
Lung cancer is a malignant tumor with high incidence and mortality in China and the
world, among which small cell lung cancer (SCLC) accounts for 13% to 17% of lung cancer,
and about 250,000 patients are diagnosed with SCLC every year in the world, and nearly
200,000 people die from it. Due to the high degree of malignancy of SCLC, it is easy to
develop distant metastasis in the early stage, and most of the patients are diagnosed in
the late stage with poor prognosis. Although SCLC is sensitive to chemotherapy and
radiotherapy and has a high remission rate after initial treatment, it is prone to
secondary drug resistance and relapse. SCLC is a low-differentiated, high-grade
neuroendocrine tumor that can be classified into limited-stage and extensive stage
(ES-SCLC). Etoposide combined with cisplatin (EP regimen) or carboplatin (EC regimen),
irinotecan combined with cisplatin (IP regimen) or carboplatin (IC regimen) are the basis
of standard first-line therapy for ES-SCLC. Immunocombined chemotherapy has also become
the first-line standard treatment for ES-SCLC, among which serplulimab + etoposide +
carboplatin is recommended by CSCO guidelines for first-line treatment. Liposomal
irinotecan is irinotecan encapsulated by liposomes, which has advantages in safety. The
study is expected to achieve good efficacy, improve the quality of life and prolong the
survival of patients by combining the immune drug serplulimab on the basis of IC regimen.
After replacing ordinary irinotecan with liposomal irinotecan, this study aims to compare
the efficacy and safety of liposomal irinotecan + carboplatin + serplulimab with the
first-line standard regimen (etoposide + carboplatin + serplulimab) in patients with
extensive stage small-cell lung cancer, providing a better basis for clinical use.
Trial design: This is a multicenter, open-label, non-comparative, randomized Phase II
clinical study. Sixty patients with extensive stage small cell lung cancer were expected
to be enrolled and randomly assigned 1:1 to either liposomal irinotecan + carboplatin +
serplulimab or etoposide + carboplatin + serplulimab for treatment. The study included a
screening period (within 28 days), a treatment period (4 cycles planned), and a follow-up
period (safety follow-up and PFS follow-up). Subjects signed informed consent and
underwent baseline examination during the screening period. Patients who met the
inclusion and exclusion criteria entered the treatment period. All subjects completed
relevant examinations specified in the protocol during treatment to observe safety,
tolerability and efficacy. The same subject received only one dosing schedule during the
study. After the treatment period, the follow-up period was entered.
Treatment regimen: Cohort 1: Liposomal irinotecan: 50mg/m2, ivgtt, d1; Carboplatin AUC=5,
ivgtt, d1; Serplulimab: 4.5mg/kg, ivgtt, d1; The drug was administered once every three
weeks for a total of 4 cycles. After 4 cycles, serplulimab is maintained until disease
progression or toxicity becomes intolerable. Cohort 2: Etoposide: 100 mg/m2, ivgtt, d1-3;
Carboplatin AUC=5, ivgtt, d1; Serplulimab: 4.5mg/kg, ivgtt, d1; The drug was administered
once every three weeks for a total of 4 cycles. After 4 cycles, serplulimab is maintained
until disease progression or toxicity becomes intolerable.
Endpoint: Primary endpoint: Progression-free survival (PFS). Secondary endpoints:
Objective response rate (ORR), disease control rate (DCR), overall survival (OS), and
outcome in brain metastases (PFS).
Safety endpoints: Incidence and severity of hematologic and nonhematologic adverse events
(NCI-CTCAE5.0).
Follow-up: After the end of the treatment period, the follow-up period was entered, which
was once every 2 months in the first year and once every 3-4 months in the second to
third year.
Statistical analysis: IBM SPSS software (version 25.0 or above) was used for statistical
analysis in this study. The measurement data were described statistically with mean,
median, standard deviation, maximum and minimum values. Count data or grade data use case
number, percentage representation.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patients fully understand the study, voluntarily participate and sign an informed
consent form (ICF)；
- Age ≥18 years；
- Patients with pathologically or histologically confirmed extensive stage small cell
Lung cancer (according to the Veterans Administration Lung Study Group, VALG staging
system)；
- The patient had not previously received any form of antitumor therapy；
- According to RECIST1.1 criteria, the patient had at least one measurable target
lesion；
- Eastern Cooperative Oncology Group（ECOG）Physical status score: 0-2；
- The expected survival time is ≥3 months；
- Absolute neutrophil count (ANC) ≥1.5×10^9/L, platelets ≥100×10^9/L, and hemoglobin
≥90 g/L (no blood transfusion, blood products, correction with granulocyte colony
stimulating factor or other hematopoietic stimulating factor within 14 days prior to
laboratory examination)；
- Serum creatinine ≤1.5 times the upper limit of normal value; AST and ALT ≤2.5 times
the upper limit of normal (≤5 times the upper limit of normal for patients with
liver invasion); Total bilirubin ≤1.5 times the upper limit of normal (≤3 times the
upper limit of normal for patients with liver invasion)；
- Women of childbearing age must have had a pregnancy test (serological) negative
within 7 days prior to enrollment and be willing to use an appropriate method of
contraception during the trial period and for 6 months after the last dose of the
test drug.
Exclusion Criteria:
- Patients with large cell neuroendocrine tumor and mixed small cell carcinoma；
- Patients with active brain metastases or central nervous system invasion； confirmed
by imaging evaluation and/or biopsy (prednisone equivalent dose ≥10mg)；
- Allergic reaction to any investigational drug or its ingredients；
- The patient has previously received other antibodies/drugs that target immune
checkpoints, such as PD-1, PD-L1, CTLA4, etc；
- Serious, uncontrolled comorbidities that could affect the study results, including
but not limited to serious infections, diabetes, or cardiovascular and
cerebrovascular disease, were identified；
- Imaging confirmed intestinal obstruction；
- It has uncontrollable ascites, abdominal infection and pyloric obstruction；
- Cardiac function and disease: a history of myocardial infarction, unstable angina
pectoris, severe unstable ventricular arrhythmia or any other arrhythmia requiring
treatment, a history of clinically serious pericardial disease, or
electrocardiographic evidence of acute ischemic or active conduction system
abnormalities in the 6 months prior to recruitment；
- Hepatitis B, hepatitis C active infection (hepatitis B surface antigen positive and
hepatitis B DNA more than 1x103 copies /mL; more than 1x103 copies /mL of HCV RNA)；
- Human immunodeficiency virus (HIV) infection (HIV antibody positive);
- Previous or current co-occurrence of other malignancies (in addition to non-melanoma
basal cell carcinoma of the skin that is effectively controlled, breast/cervical
carcinoma in situ, and other malignancies that have been effectively controlled
without treatment within the past five years);
- Pregnant and lactating women and patients of childbearing age who do not want to use
contraception;
- The investigators determined that patients were not suitable to participate in this
study.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Start date:
July 5, 2024
Completion date:
June 30, 2027
Lead sponsor:
Agency:
Zhou Chengzhi
Agency class:
Other
Collaborator:
Agency:
Sun Yat-sen University
Agency class:
Other
Collaborator:
Agency:
Hunan Cancer Hospital
Agency class:
Other
Collaborator:
Agency:
Guangdong Provincial Hospital of Traditional Chinese Medicine
Agency class:
Other
Collaborator:
Agency:
First People's Hospital of Foshan
Agency class:
Other
Collaborator:
Agency:
Affiliated Hospital of Youjiang Medical University for Nationalities
Agency class:
Other
Source:
Guangzhou Institute of Respiratory Disease
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06462105
