Brain metastases from solid tumors such as primary non-small cell lung cancer, breast cancer, hepatocellular carcinoma and malignant melanoma
Conditions
Interventions
Group A:ACT001 200mg, BID+Whole-brain radiotherapy
Group B:ACT001 400 mg, BID+ Whole-brain radiotherapy
Group C:Placebo, BID+ Whole-brain radiotherapy
Sponsors
Tianjin Medical University Cancer Institute & Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Patients with brain metastases from non-small cell lung cancer, small cell lung cancer, liver cancer, breast cancer, and melanoma (brain metastases from other solid tumors can also be included after discussion with the sponsor). The primary tumors were confirmed by histology/cytology or molecular pathology; 2. According to the investigator's evaluation, the subject can receive brain radiation therapy; 3. Patients with more than three metastatic lesions (patients with small cell lung cancer do not limit the number of brain metastases); 4. Patients with at least one measurable lesion in the brain confirmed according to iRANO standards (determined by the radiology department and clinician; If there is no measurable lesion, please ask the investigator to discuss the actual situation with the sponsor to determine whether it can be selected after judgment): 4.1 The diameter of the largest measurable lesion is greater than 1cm, and the maximum diameter of the lesion does not exceed 4.0cm; 4.2 The distance between metastases and important brain function areas meets the requirements of radiotherapy; 5. Aged >= 18 years old and = 1.0 x 10^9/L, platelets >= 50 x 10^9/L, Hb >= 8g/dl; total bilirubin = 60 (excluding motor dysfunction caused by brain tumors involving motor areas or impaired limbs); 9. Female subjects must also meet the following criteria to be considered for inclusion: 1) Infertility, defined as: (1) Have had a hysterectomy or bilateral oophorectomy, or (2) Have had bilateral tubal ligation, or (3) Have been menopausal (complete menopause >= 1 year). 2) Have fertility, but the serum pregnancy test was negative at the time of screening (within 7 days before the first trial drug administration), and agree to take medically approved contraceptive measures (such as intrauterine devices, contraceptives, or condoms) before and during the study, until 28 days after the last trial drug administration. 10. Sexually active male patients must agree to use barrier methods of contraception or be abstinent completely. 11. Agree to sign an informed consent form before entering the study.
Exclusion criteria
Exclusion criteria: 1. Patients with brain metastases from non-small cell lung cancer and breast cancer with positive driving genes of specific target drugs: non-small cell lung cancer with EGFR mutation, ALK fusion gene positive and ROS1 fusion gene positive; HER-2 positive breast cancer. 2. Patients who have previously had brain radiation therapy. 3. The subject has an uncontrollable infection (systemic infection within 4 weeks before enrollment). 4. Suffered from other malignant tumors (except for fully treated cervical carcinoma in situ, skin basal cell or squamous cell skin cancer, local prostate cancer after radical operation, and ductal carcinoma in situ of the breast) other than the primary tumor within 5 years before screening. 5. Anti-HIV (+) or anti-HCV (+) or a specific antibody (TPPA) positive or active hepatitis B. 6. The subject had severe heart disease before enrollment, such as unstable angina, myocardial infarction, heart failure (New York Heart Association heart function classification > grade II), or stroke (except for lacunar infarction). 7. Patients with hypertension who cannot be controlled by drugs (systolic blood pressure >= 160mmHg and diastolic blood pressure >= 100mmHg after taking antihypertensive drugs). 8. Patients who are unable to take medication or suffer from gastrointestinal absorption disorders. 9. Patients who are found to have active cerebral hemorrhage. 10. Those who are known to be allergic to the trial drug or its analogous compound, or any component in the trial drug prescription. 11. Received other anti-cancer treatments, such as chemotherapy that can pass the blood-brain barrier, biological therapy or targeted therapy, immunotherapy, radiation therapy or electric field therapy, that have a therapeutic effect on brain metastases from solid tumors within 4 weeks before the trial drug administration. 12. The toxicity caused by the previous anti-tumor treatment has not been restored, and it is defined as follows: According to the evaluation standard of CTCAE V 5.0 version, the toxicity has not been restored to <= 2 (except for hair loss, alkaline phosphatase, glutamyl transpeptidase (GGT)). However, after discussion with the investigator and sponsor, stable toxicity may be allowed. 13. Pregnant or lactating women. 14. Patients who have participated in other clinical studies within 4 weeks before the trial medication. 15. Other reasons for not participating in this study according to the judgment of the investigators.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Adverse events;One-year progression-free survival rate of intracranial tumor; | — |
Secondary
| Measure | Time frame |
|---|---|
| QLQ-C30 Score of Quality of Life Measurement Scale for Cancer Patients;Objective response rate (ORR) of intracranial tumors on the 30th day after the end of radiotherapy;Progression-free survival of intracranial tumor;Overall survival;Hormone dose during radiotherapy;Radiation Therapy Cooperative Group (RTOG) Advanced Brain Injury Classification;KPS score; | — |
Countries
China
Contacts
Public ContactWang Ping, Pang Qingsong
Tianjin Medical University Cancer Institute & Hospital
Outcome results
None listed