Trial Title:
Adebelizumab Combined With Chemotherapy and Radiotherapy Treat ES-SCLC
NCT ID:
NCT06125041
Condition:
Extensive Small Cell Lung Cancer
Conditions: Official terms:
Lung Neoplasms
Small Cell Lung Carcinoma
Carboplatin
Etoposide
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Adebelizumab+Carboplatin+Etoposide+Concurrent Radiotherapy
Description:
Eligible patients will receive the following treatment schemes:
adebelizumab+carboplatin+etoposide, with one treatment cycle every three weeks. After 4-6
cycles, adebelizumab maintenance therapy combined with concurrent radiotherapy will be
given, and conventional radiotherapy will be given to chest lesions (2Gy*(20-30)f), brain
(3Gy*10f)/ bone (3Gy*10f)/ adrenal gland. Immunotherapy is suspended during radiotherapy
for chest lesions and lymph nodes in mediastinum, and immunotherapy is given 1-2 weeks
after radiotherapy. Radiotherapy for other metastatic lesions can be carried out
simultaneously with immunotherapy.
Arm group label:
treatment group
Other name:
Adebelizumab Combined With Chemotherapy and Sequential Adebelizumab Combined With Radiotherapy in the Treatment of Newly Diagnosed Extensive Small Cell Lung Cancer
Summary:
To observe the efficacy and safety of adebelizumab combined with chemotherapy and
sequential adebelizumab combined with radiotherapy in the treatment of newly diagnosed
extensive small cell lung cancer.
Detailed description:
This study is a one-arm, multi-center and exploratory study. Eligible patients will
receive the following treatment schemes: adebelizumab+carboplatin+etoposide, with one
treatment cycle every three weeks. After 4-6 cycles, adebelizumab maintenance therapy
combined with concurrent radiotherapy will be given, and conventional radiotherapy will
be given to chest lesions (2Gy*(20-30)f), brain (3Gy*10f)/ bone (3Gy*10f)/ adrenal gland.
Immunotherapy is suspended during radiotherapy for chest lesions and lymph nodes in
mediastinum, and immunotherapy is given 1-2 weeks after radiotherapy. Radiotherapy for
other metastatic lesions can be carried out simultaneously with immunotherapy.
Research population: patients with extensive small cell lung cancer diagnosed by
histopathology or cytology, both male and female, aged 18-75 years old, who have not
received systemic treatment for small cell lung cancer before. 51 patients are planned to
be enrolled.
Main research end point： PFS(RECIST v1.1 standard) evaluated by researchers. Secondary
end point
Key secondary study endpoints:
The incidence of adverse reactions above grade 3 in patients evaluated according to
CTCAE5.0 version 5.0.
Other secondary study endpoints:
OS； ORR(RECIST v1.1 standard) evaluated by researchers; DoR； evaluated by the researcher;
DCR； assessed by the researcher; PFS rate at 6 months and 1 year OS rate at 1 year and 2
years. The end point of exploratory research Explore the biomarker related to curative
effect.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Age 18-75 years old, both male and female;
- Extensive small cell lung cancer (metastatic lesions ≤3 organs, ≤5 lesions)
confirmed by histology or cytology (according to the Veterans Administration Lung
Study Group (VALG staging), including asymptomatic brain metastasis, multiple lung
metastases, supraclavicular or mediastinal lymph node metastasis, bone metastasis,
adrenal metastasis, retroperitoneal lymph node metastasis, etc.;
- The score of ECOG physical condition is 0~1;
- Never received first-line systemic therapy for ES-SCLC or immune checkpoint
inhibitors before;
- Previous surgical treatment did not include adjuvant therapy such as radiotherapy
and chemotherapy, and there was a five-treatment interval of at least 6 months from
the diagnosis of extensive SCLC to the last chemotherapy and radiotherapy.
- It is necessary to be able to provide tumor tissue samples before the experimental
treatment, which can be archived within 6 months before the first dose of the
research drug or freshly obtained. Specimens should be fixed in formalin and
embedded in paraffin (FFPE), and at least 10 4~6μm thick sections can be cut out for
staining and detection. Specimens that do not accept fine needle aspiration biopsy,
cytological smears of pleural effusion drainage and centrifugation, bone lesions
without soft tissue components or decalcified bone tumor specimens, and tissues
drilled for biopsy are not enough for biomarker detection; Tissue samples should be
submitted within 4 weeks before or after signing the notice, allowing research
participants to provide Before the tumor tissue samples were taken into the study;
- Estimated survival time ≥8 weeks;
- There is a measurable lesion defined by RECIST standard v1.1: only when a previously
irradiated lesion shows definite disease progression after radiotherapy and the
previous lesion is not the only lesion can it be considered as a measurable lesion;
- Women of childbearing age must have a serum pregnancy study within 7 days before the
first medication, and the result is negative. Participants in the study of women of
childbearing age and male participants whose partners are women of childbearing age
must agree to contraception within 24 weeks after signing the informed consent form
to the last administration of the study drug;
- Before the first dose of study drug, the laboratory test value meets the following
conditions:
1. Blood routine (no blood transfusion and no use of hematopoietic stimulating
factors within 14 days before screening) Material correction): White blood cell
(WBC) ≥ 3.0× 10^9/L; Absolute neutrophil count (ANC) ≥ 1.5× 10^9/L; Platelet
(PLT) ≥ 100× 10^9/L； Hemoglobin (HGB) ≥ 9.0g/dl;
2. Liver function: aspartate aminotransferase (AST) ≤ 2.5 x ULN; Alanine
aminotransferase (ALT) ≤ 2.5 x ULN, and ALT and AST≤5 x ULN； of participants in
liver metastasis study; Total bilirubin (TBIL) ≤ 1.5 x ULN (except Gilbert
syndrome ≤ 3.0 mg/dl);
3. Renal function: serum creatinine ≤1.5 x ULN or creatinine clearance rate (CRCL)
≥ 50 ml/minute;
4. Coagulation function: international normalized ratio (INR) ≤ 1.5 x ULN,
activated partial thromboplastin time (APTT) ≤ 1.5 x ULN (only applicable to
patients who have not received anticoagulant therapy at present, and patients
who are currently receiving anticoagulant therapy should receive stable dose of
anticoagulant therapy);
5. Others: lipase ≤1.5 x ULN (if lipase > 1.5 x ULN without clinical or imaging
confirmation of pancreatitis, you can be included in the group); Amylase ≤1.5 x
ULN (if amylase > 1.5 x ULN without clinical or imaging confirmation of
pancreatitis, you can be included in the group); Alkaline phosphatase (ALP) ≤
2.5 ULN, and ALP ≤ 5 ULN for participants in liver metastasis or bone
metastasis research.
- The study participants voluntarily joined the study, signed the informed consent,
and had good compliance and cooperated with the follow-up.
Exclusion Criteria:
- Symptomatic brain metastasis and liver metastasis;
- The effusion in the third space with clinical symptoms needs repeated drainage, such
as pericardial effusion, pleural effusion and peritoneal effusion that cannot be
controlled by pumping or other treatments;
- Uncontrollable or symptomatic hypercalcemia;
- Other malignant tumors occurred less than 5 years before the first dose, except for
cervical carcinoma in situ, basal cell or squamous cell skin cancer, local prostate
cancer after radical surgery and ductal carcinoma in situ after radical surgery
(hormone therapy for non-metastatic prostate cancer or breast cancer is allowed);
- Active, known or suspected autoimmune diseases (see Annex 4) include but are not
limited to myasthenia gravis, autoimmune hepatitis, systemic lupus erythematosus,
rheumatoid arthritis and inflammatory bowel disease. Allow type I diabetes (blood
sugar can be controlled by insulin treatment), residual hypothyroidism caused by
autoimmune thyroiditis that only needs hormone replacement therapy, or the situation
that it is not expected to recur in the absence of external stimulus; In patients
with eczema, psoriasis, chronic lichen simplex or only vitiligo (psoriasis arthritis
should be excluded), if the skin rash coverage area is less than 10% of the body
surface area, the disease has been fully controlled at baseline and only low titer
is needed.
- Local steroid therapy, the basic disease did not appear acute aggravation in the
past 12 months (without psoralen plus ultraviolet radiation [PUVA], methotrexate,
retinoids, biological agents, oral calcineurin inhibitors, high titer or oral
steroids) can enter the study;
- Previously received any T cell co-stimulation or immune checkpoint treatment,
including but not limited to cytotoxic T lymphocyte associated antigen-4 (CTLA-4)
inhibitor, PD-1 inhibitor, PD-L1/2 inhibitor or other drugs targeting T cells;
- Use corticosteroids (> 10 mg/day prednisone or equivalent dose) or other
immunosuppressants within 14 days or less before the first dose of study drug.
Inhalation or local use of steroids and adrenal glands instead of steroids is
allowed without active autoimmune diseases;
- HBsAg positive and the number of copies of HBV DNA is greater than the upper limit
of the normal value of the laboratory of the research center (1000 copies /ml or
500IU/ml), or HCV positive (HCV RNA or HCV Ab detection indicates acute and chronic
infection); Known HIV positive history or known Acquired Immune Deficiency Syndrome
(AIDS);
- Suffering from a history of idiopathic pulmonary fibrosis, organized pneumonia (such
as bronchiolitis obliterans), drug-induced pneumonia, radiation pneumonia requiring
steroid treatment or active pneumonia with clinical symptoms; Or other moderate or
severe lung diseases that seriously affect lung function (patients with a history of
radiation pneumonia (fibrosis) in the radiation area can participate in this study);
- Active pulmonary tuberculosis, TB) or research participants with a history of active
pulmonary tuberculosis infection within 48 weeks or less before screening,
regardless of treatment;
- There are severe infections when entering the group, including but not limited to
infection complications, bacteremia, severe pneumonia, etc. that require
hospitalization;
- Have undergone major surgery within 28 days before joining the group, or plan to
undergo major surgery during the study period;
- Use attenuated live vaccine within 28 days before enrollment, or expect to use such
attenuated live vaccine during the study period (patients are not allowed to receive
attenuated live influenza vaccine within 4 weeks before randomization, during the
treatment period and within 5 months after the last administration of SHR-1316/
placebo);
- Have serious cardiovascular diseases, such as heart failure of new york Heart
Association (NYHA) grade 2 or above, unstable angina pectoris, unstable arrhythmia,
myocardial infarction or cerebrovascular accident within the first 3 months at
random;
- patients who have received allogeneic bone marrow transplantation or solid organ
transplantation in the past;
- It is known to be allergic to research drugs or excipients, and it is known to have
a serious allergic reaction to any kind of monoclonal antibody; Have a history of
carboplatin or etoposide allergy;
- Have received any other experimental drug treatment or participated in another
interventional clinical study within 4 weeks before signing ICF;
- Within one week before joining the group, he received systemic immunosuppressive
drugs (including but not limited to glucocorticoid, cyclophosphamide, azathioprine,
methotrexate, thalidomide and anti-tumor necrosis factor [anti -TNF] drugs).
Patients receiving short-term, systemic immunosuppressant therapy, such as
glucocorticoid for nausea, vomiting, or allergic reaction management or preventive
medication, can be enrolled in the study with the approval of the researcher.
Inhaled corticosteroids are allowed to treat patients with chronic obstructive
pulmonary disease, mineralocorticoids such as hydrocortisone to treat postural
hypotension, and low-dose glucocorticoid supplements to treat adrenal insufficiency;
- Known mental illness, alcoholism, inability to quit smoking, drug abuse or substance
abuse; According to the judgment of the researcher, there are other factors that may
lead to the forced termination of the study, such as non-compliance with the
protocol, other serious diseases (including mental illness) requiring combined
treatment, serious abnormal laboratory examination, family or social factors, which
will affect the safety of the study participants, or the collection of data and
samples.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
The First Affiliated Hospital of Shandong First Medical University
Address:
City:
Jinan
Country:
China
Status:
Recruiting
Contact:
Last name:
Jiandong Zhang
Phone:
+8653189268118
Email:
zhangid165@sina.com
Start date:
October 30, 2023
Completion date:
December 31, 2026
Lead sponsor:
Agency:
Qianfoshan Hospital
Agency class:
Other
Source:
Qianfoshan Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06125041
