Small Cell Lung Cancer who have Brain Metastases
Conditions
Interventions
Treatment Group:ACT001 400 mg, BID+WBRT
Placebo Group:Placebo, BID+WBRT
Sponsors
Affiliated Cancer Hospital of Shandong First Medical University (Shandong Institute of Cancer Prevention and Treatment and Shandong Cancer Hospital)
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Patients with histologically or cytologically confirmed small cell lung cancer (SCLC) (excluding patients with combined SCLC), patients have received second-line and developed brain metastases (regardless of the number of brain metastasis lesions). Patients can be included if new brain metastasis lesions occur during or after the first-line treatment, or if the original brain metastasis lesions progress. 2. Patients deemed suitable to receive whole brain radiation therapy assessed by the investigators. 3.Presence of at least one measurable intracranial lesion confirmed per RECIST v1.1 (determined by radiology and clinical assessment): The maximum diameter of the largest measurable lesions should generally be 4 cm or = 18 years old and = 1.5×10^9 /L, platelet >= 75×10^9/L, hemoglobin (Hb) >= 80 g/L, and without transfusion within 14 days prior to first dose (patients with values below these thresholds potentially attributable to prior systemic therapy (e.g., chemotherapy) may receive growth factor support (e.g., erythropoietin, thrombopoietin, G-CSF). Reassessment after treatment showing values meeting criteria permits enrollment.). Total bilirubin =50ml/min (as assessed by the investigator to be acceptable for enhanced MRI/CT); International Normalized ratio (INR) = 70 (excluding neurological deficits solely due to metastatic motor cortex involvement or unrelated limb disabilities). 8. Female patients should also meet the following criteria to be considered for inclusion: (1) No-childbearing potential, defined as: history of hysterectomy or bilateral oophorectomy, or status after bilateral tubal ligation, or postmenopausal status (complete cessation of menses >= 1 year). (2) Childbearing potential must demonstrate a negative serum pregnancy test at the time of screening (within 7 days prior to the first study drug administration) and who agreed to use medically approved contraceptive methods (such as intrauterine devices, contraceptives, or condoms) before and during the study until 28 days after the last study drug administration. 9. Sexually active male patients must agree to use a barrier contraception method or practice complete abstinence. 10. Consent to sign informed consent before enrollment.
Exclusion criteria
Exclusion criteria: 1. Patients who have previously received whole brain radiotherapy(WBRT) and / or tumor treating fields therapy (those who have received previous localized treatment for intracranial tumor, and are deemed by the investigators as eligible for additional WBRT may be enrolled.) 2. Patients with concomitant leptomeningeal metastasis. 3. Patients requiring urgent intervention for conditions such as superior vena cava syndrome, spinal cord compression, brain herniation, etc. 4. Patients experiencing repeated major seizures. 5. Patients assessed by the investigator as having an active infection at the time of screening. 6. Patients diagnosed with other malignancies other than the primary tumor within 5 years prior to screening (except for adequately treated carcinoma in situ of the cervix, basal cell or squamous cell skin cancer, localized prostate cancer treated with radical surgery, and ductal carcinoma in situ of the breast.) 7. Patients with uncontrolled pleural effusion, pericardial effusion, or ascites (requiring recurrent drainage once a month or more frequently, or drainage within 2 weeks prior to screening). 8. Patients with active hepatitis B and/or hepatitis C, i.e., HBsAg positive and/or HBcAb positive with HBV DNA positive and/or anti-HCV positive with HCV RNA positive; 9. Patients with a positive Human immunodeficiency virus (HIV) antibody test; 10. Patients with a history of major cardiovascular or cerebrovascular events within 6 months prior to the fist dose of the investigational drug, such as congestive heart failure (New York Heart Association Class >=2), acute myocardial infarction, unstable angina, QTc > 450 msec in males or 470 msec in females, stroke, transient ischemic attack, deep vein thrombosis or pulmonary embolism, etc. 11. Patients with hypertension that cannot be controlled by medication (systolic blood pressure =160 mmHg and/or diastolic blood pressure =100 mmHg despite antihypertensive medication). 12. Patients with gastrointestinal disorders that may interfere with oral administration or drug absorption, or patients with severe gastrointestinal disease with 4 weeks prior to the first dose (e.g., refractory nausea, refractory diarrhea, colitis, etc.) 13 Patients with a history of inflammatory bowel disease or an autoimmune disease deemed by the investigator as unsuitable for participation in this study (e.g., systemic lupus erythematosus, vasculitis, etc.) (this criterion applies only to subjects receiving immune checkpoint inhibitors such as PD-1/PD-l1 antibodies during the trial). 14. Patients requiring systemic glucocorticoid therapy (consecutive use > 3 days, equivalent to > 4 mg dexamethasone daily) or other immunosuppressive therapy with 14 days prior to the first investigational drug dose or planned during the study (excluding corticosteroids used for CNS metastases management and as premedication for chemotherapy) or patients with chronic conditions such as severe radiation pneumonitis or severe interstitial lung disease. 15. Patients with a history of allogeneic organ transplantation or allogeneic peripheral blood stem cell /bone marrow transplantation; 16. Patients who known allergy to the investigational drug, its analogs, or any components of the investigational drug formulation; 17. Patients who have received Bevacizumab or its biosimilars within 4 weeks prior to investigational drug administration (to aviod potential interference with baseline intracranial lesion MRI assessments); 18. Patien
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall survival; | — |
Secondary
| Measure | Time frame |
|---|---|
| ORR of intracranial tumors 3 months after radiotherapy;Intracranial tumors ORR;Intracranial tumors PFS;Intracranial tumors TTP;Intracranial tumors DPR;Intracranial tumors DoR;The incidence rate of SAE within 3 months after radiotherapy;The proportion of subjects who were visited 12 weeks after completing radiotherapy;The incidence rate of = grade 2 AE related to WBRT;Change in QLQ-C30 score;Change in the score of the Montreal Cognitive Assessment (MoCA) scale; | — |
Countries
China
Contacts
Public ContactJinming Yu
Affiliated Cancer Hospital of Shandong First Medical University (Shandong Institute of Cancer Prevention and Treatment and Shandong Cancer Hospital)
Outcome results
None listed