Small cell lung cancer and non-small cell lung cancer with brain metastases
Conditions
Interventions
Treatment group:ACT001 400 mg BID+ whole brain Radiation Therapy
Placebo group:Placebo, BID plus whole brain radiation therapy
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: To be included in this study, the following inclusion criteria must be met: 1. Patients with histologically or cytologically confirmed lung cancer (small cell lung cancer and non-small cell lung cancer) with brain metastases: small cell lung cancer: two lines above treatment, and patients with brain metastasis; non-small cell lung cancer: drive negative genetic only.Second-line treatment and above with brain metastases. 2. Subjects assessed by the investigators could receive whole brain radiation therapy. 3. > 3 brain metastases (small cell lung cancer patients do not limit the number of brain metastases). 4. Confirm that there is at least one measurable lesion in the brain according to RECIST v1.1 criteria (as determined by radiologists and clinicians) : maximum measurable lesions is not more than 4 cm diameter ( 4 cm and 6 cm do after lesions and consider into the group of local plus the amount of radiation, the researchers can also be considered after assessment group); metastases with important distance conform to the requirements of the related radiotherapy of brain functional area. 5. Age =18 years old and =75 years old, regardless of gender. 6. Normal organ function:Absolute neutrophil count (ANC) = 1.5×10^9 /L, platelet =75×10^9/L, hemoglobin (Hb) = 80 g/L, and no blood transfusion or treatment with growth factors such as erythropoietin, thrombopoietin, and granulocyte colony stimulating factor within 14 days prior to the first dose;Total bilirubin = 2.0× upper normal limit (ULN);Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 3.0×ULN (5.0 ×ULN if liver metastasis exists);Serum creatinine = 1.5×ULN or creatinine clearance =50ml/min (as assessed by the investigator to be acceptable for enhanced MRI/CT);International Normalized ratio (INR) =1.5×ULN and activated partial thromboplastin time (APTT) =1.5×ULN. 7. Life expectancy is at least 12 weeks. 8. KPS score =70 (excluding motor dysfunction due to brain tumor involvement in motor areas or limb insufficiency). 9. Female patients should also meet the following criteria to be considered for inclusion: a) Sterile, defined as: have received a hysterectomy and bilateral oophorectomy, and or have received bilateral tubal ligation, or postmenopausal (completely menopause or 1 year). b) Fertile female patients with 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. 10. Sexually active male patients must consent to barrier contraception or complete abstinence. 11. Consent to sign informed consent before enrollment.
Exclusion criteria
Exclusion criteria: Those who meet any of the following criteria will be excluded: 1. Patients who had previously received whole brain radiotherapy (those who had previously received local treatment for intracranial tumor lesions, and the researchers believed that they could receive whole brain radiotherapy again were allowed to be included in the group). 2. Patients with meningeal metastasis. 3. Patients with positive driver genes such as EGFR, ALK, ROS1, NTRK and MET. 4. Patients complicated with superior vena cava syndrome, spinal cord compression, cerebral hernia, etc., requiring timely intervention. 5. The investigators assessed that the patient had active infection at the time of screening. 6. Other malignancies other than the primary tumor within 5 years prior to screening (except adequately treated cervical carcinoma in situ, skin basal cell or squamous cell skin cancer, local prostate cancer after radical surgery, and ductal carcinoma in situ of the breast). 7. Patients with active hepatitis B and/or hepatitis C, i.e., HBsAg positive and/or HBcAb positive with HBV DNA positive (i.e. =2000 IU/ml or 104 copy numbers /ml) and/or anti-HCV positive with HCVRNA positive. 8. Human immunodeficiency virus (HIV) antibody positive patients. 9. Major cardiovascular and cerebrovascular diseases occurred within 6 months prior to drug administration in the first study.Such as congestive heart failure (New York College of Cardiology heart function scale =2), acute myocardial infarction, unstable angina, QTc > 450 msec in men or 470 msec in women, stroke, transient ischemic attack, deep vein thrombosis or pulmonary embolism, etc. 10. Patients with hypertension that cannot be controlled by medication (systolic blood pressure =160 mmHg and/or diastolic blood pressure =100 mmHg after taking antihypertensive medications). 11. Patients are unable to take medications orally or have gastrointestinal absorption dysfunction. 12. A history of inflammatory bowel disease or a history of autoimmune diseases, such as systemic lupus erythematosus and vasculitis, that have been determined by the investigator to be ineligible for participation in this study (exclusion criteria are only for subjects who require immune checkpoint inhibitors such as PD1/PDL1 antibodies during the course of the study). 13. Systemic glucocorticoid therapy (more than 4 mg of dexamethasone daily or equivalent glucocorticoid for > 3 days prior to initial administration of the study drug or planned during the study period,Patients with chronic diseases such as severe radiation pneumonia or severe interstitial pneumonia treated with other immunosuppressive therapy (except glucocorticoids for brain metastases and preconditioning before chemotherapy). 14. Patients with a history of allograft or allograft peripheral blood stem cell/bone marrow transplantation. 15. Known allergy to the investigational drug or its similar compounds, or to any component of the investigational drug prescription. 16. Received an antiangiogenic drug (bevacizumab) within 4 weeks prior to study drug administration;Other anti-cancer therapies, such as chemotherapy that can cross the blood-brain barrier (temozolomide), antiangiogenic agents (anrotinib), radiation therapy, or electric field therapy, were received within 2 weeks prior to administration. 17. Toxicity due to previous antitumor therapy has not recovered, defined as: toxicity has not recovered to = grade 2 according to the Common adverse event evaluation crit
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective response rate of intracranial tumor within 3 months (ORR); | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall survival (OS);Intracranial tumor progression time (TTP);Depth of remission of intracranial tumor (DPR);Incidence of serious adverse events (SAE);The QLQ-C30 score has changed;Incidence of late neurological impairment events caused by WBRT;Proportion of subjects interviewed 12 weeks after completion of radiotherapy;Incidence of =2 grade WBRT-associated AE;PK parameters for single and multiple administration; | — |
Countries
china
Contacts
Public ContactYu jinming
Affiliated Cancer Hospital of Shandong First Medical University (Shandong Institute of Cancer Prevention and Treatment and Shandong Cancer Hospital)
Outcome results
None listed