Clinical trial NCT05638425: Radiotherapy Combined With PD-1 Inhibitors and Chemotherapy in the Treatment of NSCLC Patients With Symptomatic Brain Metastases
Official title: An Observational Study on the Efficacy and Safety of Radiotherapy Combined With PD-1 Inhibitors and Chemotherapy in the Treatment of NSCLC Patients With Symptomatic Brain Metastases
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Non-small Cell Lung Cancer Metastatic
Brain Metastases
Keywords: radiotherapy
PD-1
symptomatic brain metastases
non-small cell lung cancer
Lead sponsor: Xiangya Hospital of Central South University
Sponsor class: OTHER
Collaborators: name: Wu Jieping Medical Foundation
First posted: 2022-12-06
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: NSCLC Patients With Symptomatic Brain Metastases

Brief summary: This is a prospective, single-center observational clinical study aimed at the efficacy and safety of radiotherapy combined with PD-1 inhibitors and chemotherapy in the treatment of Chinese patients with symptomatic NSCLC with brain metastases.

Detailed description: Radiotherapy is carried out within 4 weeks after the first dose of PD-1 inhibitor; radiotherapy is determined according to the patient's condition; the use of PD-1 inhibitors and chemotherapy is based on the actual product instructions.

From December 2021 to December 2023, after the patients signed the informed consent, they will be included in this observational study after being assessed as meeting the inclusion criteria. A total of 20 cases are planned to be included for research analysis. All eligible patients meeting the inclusion and exclusion criteria will be invited to participate in this study. Patients included in the study will be solicited to allow efficacy evaluation and survival follow-up during the study and after treatment. Patients were considered to be on study unless the patient died, was withdrawn from the study, was lost to follow-up, or the study was terminated. Patients do not need to visit a doctor or receive evaluation specifically because of the study, and the study doctor evaluates the patients based on clinical practice.

Since this study is an observational study, the diagnosis and treatment process listed in the protocol is a clinically recommended process and is not mandatory. Treatment and clinical visit schedules for enrolled patients were determined by clinicians based on routine practice. This study collects patient information, including safety and efficacy data, based on routine diagnosis and treatment procedures. Although the protocol does not mandate clinical visits, physicians are encouraged to follow up patients who have not been seen for at least 6 months to collect treatment-related data and determine patient survival. Patients will be considered lost to follow-up if they have not been seen for at least 1 year.

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 18 years old; patients with metastatic NSCLC with at least one measurable brain metastases, the longest diameter of the brain metastases is 0.5 to 3 cm, and the brain metastases have not received radiotherapy; stable neurological symptoms and/or are receiving Corticosteroid therapy. In addition, the following conditions are raised:

1. Patients with negative driver-gene mutations who have not received systemic treatment before, and patients who have progressed after receiving neoadjuvant or adjuvant therapy, and the interval between disease progression or recurrence and the end of the last chemotherapy drug treatment is at least 6 months, and is allowed to enter this study;
2. Patients with known EGFR sensitive mutation, ALK rearrangement or ROS1 fusion must have received at least one EGFR or ALK, ROS1 fusion inhibitor treatment and had disease progression or drug intolerance.
3. Subjects with neurological symptoms can receive dexamethasone within 10 days before the first treatment, but the total daily dose is stable at no more than 4 mg or other Corticosteroids at the same dose. Subjects with neurologic symptoms but not receiving steroids should experience no seizures within 10 days prior to first treatment.

2. For patients with non-brain oligometastases, according to Response Evaluation Criteria in Solid Tumors Version 1.1 (mRECIST v1.1), there is at least 1 measurable or evaluable lesion in addition to brain metastases.

3. The Eastern Cooperative Oncology Group Physical Status Score (ECOG PS score) is 0-2 points.

4. The patient has a clear mind, can answer correctly, and has basically normal vision, etc., and can cooperate with cognitive function assessment 5. Expected survival time ≥ 12 weeks. 6. The patient has adequate organ and bone marrow functions, as defined below:

1. Blood routine: absolute neutrophil count ≥1.5×109/L; platelet count ≥100×109/L; hemoglobin content ≥9.0 g/dL.
2. Liver function: serum total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); for patients with HCC, liver metastases, or a history/suspect of Gilbert syndrome (persistent or recurrent hyperbilirubinemia , mainly high unconjugated bilirubin, no evidence of hemolysis or liver disease), TBIL ≤ 3 × ULN; for patients without HCC and liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN; for patients with HCC or with liver metastases, ALT or AST ≤ 5 × ULN.
3. Renal function: serum creatinine (Cr) ≤ 1.5×ULN or creatinine clearance (CCr) ≥ 50mL/min; urine test paper test results show urine protein \<2+.
4. Coagulation function: activated partial thromboplastin time (APTT) and international normalized ratio (INR) ≤ 1.5×ULN.

Exclusion Criteria:

1. Receive live attenuated vaccine within 4 weeks before enrollment or plan to receive live attenuated vaccine during the study.
2. Active, known or suspected autoimmune disease.
3. Known history of primary immunodeficiency.
4. Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
5. Female patients who are pregnant or breastfeeding.
6. Untreated acute or chronic active hepatitis B or hepatitis C infection. Patients who are receiving antiviral treatment will be judged by doctors according to the individual conditions of the patients under the condition of monitoring the virus copy number.
7. History of dementia, Alzheimer's disease, Parkinson's disease and other diseases that can cause cognitive dysfunction
8. History of schizophrenia, severe anxiety, depression, or other mental illnesses
9. Uncontrolled concurrent diseases, including but not limited to:

   1. HIV-infected persons (HIV antibody positive).
   2. Serious infection that is active or poorly controlled clinically.
   3. Serious or uncontrolled systemic disease (such as severe mental, neurological disease, epilepsy or dementia, unstable or uncompensated respiratory, cardiovascular, hepatic or renal disease, uncontrolled hypertension \[i.e. Evidence of greater than or equal to CTCAE grade 2 hypertension after drug treatment\]).
   4. Active bleeding or new thrombotic disease is taking therapeutic dose of anticoagulant drugs or bleeding tendency

Primary outcomes:
measure: Intracranial clinical benefit rate (CBR)
timeFrame: 6 months
measure: Intracranial progression-free survival (PFS)
timeFrame: 1 year
Secondary outcomes:
measure: Intracranial objective response rate (ORR)
timeFrame: 1 year
measure: Extracranial clinical benefit rate (CBR)
timeFrame: 1 year
measure: Extracranial objective response rate (ORR)
timeFrame: 1 year
measure: Extracranial progression-free survival (PFS)
timeFrame: 1 year
measure: Clinical benefit rate (CBR)
timeFrame: 1 year
measure: Objective response rate (ORR)
timeFrame: 1 year
measure: Progression-free survival (PFS)
timeFrame: 1 year
measure: Overall survival (OS)
timeFrame: 1 year
measure: Incidence of neurological adverse events
timeFrame: 1 year
measure: Incidence of severe adverse events
timeFrame: 1 year
measure: Rate of decline in cognitive function
timeFrame: 1 year
Other outcomes:
Locations:
city: Changsha
country: China
facility: Xiangya Hospital, Central South University
state: Hunan
Study officials:
References: