Clinical trial NCT04768075: Camrelizumab Combined With SRT/WBRT and Chemotherapy in Patients With Brain Metastases of Driven Gene-negative NSCLC
Official title: Randomized, Double-blind, Placebo-controlled, Multi-center Study of Camrelizumab Combined With SRT/WBRT and Chemotherapy in Patients of NSCLC With Brain Metastases of Driven Gene-negative and Not Received Systemic Chemotherapy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Non-Small-Cell Lung Cancer
Lead sponsor: Guangdong Association of Clinical Trials
Sponsor class: OTHER
First posted: 2021-02-24
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is a randomized, double-blind, placebo-controlled, multi-center clinical study. Target population is patients with stage IV non-small cell lung cancer who had not received systemic chemotherapy. Study objective is to compare the efficacy and safety of Camrelizumab + carboplatin/cisplatin + pemetrexed /paclitaxel / albumin paclitaxel ± SRT/WBRT with placebo + carboplatin/cisplatin + pemetrexed /paclitaxel / albumin paclitaxel ± SRT/WBRT. Camrelizumab is a humanized anti-PD1 IgG4 monoclonal antibody.

Detailed description: Detailed Description:

In this study, eligible subject will be randomized into study arm or control arm to accept study treatment. Paticipant was confirmed without EGFR activating mutation or ALK fusion and received no prior systemic therapy. Patients would receive Camrelizumab/placebo in combination with chemotherapy for 4-6 cycles，non-squamous subject followed by Camrelizumab/placebo + pemetrexed as maintenance treatment until progression or unacceptable toxicity, squamous subject followed by Camrelizumab/placebo as maintenance treatment until progression or unacceptable toxicity, Camrelizumab/placebo for a maximum of 2 years.

Eligibility criteria: Inclusion Criteria:

1. Histological or cytological diagnosis of non-small cell lung cancer（NSCLC）;
2. MRI confirmed brain parenchyma metastasis, ≥ 3 brain lesions, or 1-2 brain lesions but not suitable for local treatment or refused local treatment. At least one brain measurable lesion ≥ 5mm . Included with or without neurological symptoms;
3. Has not received prior systemic treatment for metastatic NSCLC. Subjects who have received prior neo-adjuvant, adjuvant chemotherapy, or chemoradiotherapy with curative intent must have experienced interval of at least 12 months from diagnosed of advanced or metastatic disease since the end of surgery;
4. Has confirmation that epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK)-directed therapy is not indicated;
5. Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status;
6. Has adequate organ function;
7. Women of childbearing age must undergo a serological pregnancy test within 7 days before the first dose with negative results. Subjects willing to use an effective contraceptive method during the study and within 90 days after the last dose of study medication;
8. Subjects should be able to follow the research and follow-up procedures;
9. Subjects should be voluntarily participating in clinical studies and informed consent should be signed;

Exclusion Criteria:

1. Brain metastases with hemorrhage；
2. Meningeal involvement with metastatic carcinoma;
3. Subjects with ROS1 mutation, RET fusion positive, BRAF V600E mutation, NTRK fusion positive;
4. Participated in other clinical trials, or finish other clinical trials within 4 weeks;
5. Subject was received irradiation of brain;
6. Subjects have received solid organ or blood system transplantation;
7. Active autoimmune diseases requiring systemic treatment (such as the use of disease remission drugs, corticosteroids or immunosuppressants) occurred within 2 years before the first administration. Alternative therapy (such as thyroxine, insulin or physiological corticosteroids for adrenal or pituitary insufficiency) is not considered systemic therapy;
8. Subjects diagnosed immunodeficiency or receiving systemic glucocorticoid therapy or any other form of immunosuppressive therapy of non-related tumor within 7 days before the first dose; allowed physiological dose of glucocorticoid (≤10 mg/day Prednisone or equivalent);
9. Within 1 year before the first dose, there was a history of non-infectious pneumonia or interstitial lung disease requiring glucocorticoid treatment;
10. Subjects with grade II or above myocardial ischemia or myocardial infarction and poorly controlled arrhythmias (QTc interval \> 450 ms for males and QTc interval \> 470 ms for females). Subjects with grade III-IV cardiac insufficiency or with left ventricular ejection fraction (LVEF) less than 50% according to NYHA criteria;
11. Has known history of Human Immunodeficiency Virus (HIV)；
12. Untreated active hepatitis B；
13. Subjects have active hepatitis B；
14. Subjects have severe infections within 4 weeks of the first dose of study treatment；
15. Subjects with clinically significant bleeding symptoms or with obvious bleeding tendency in the first month;
16. Women who are pregnant or lactating；
17. Has known allergy to Camrelizumab, or pemetrexed, or paclitaxel, or albumin paclitaxel, or carboplatin, or cisplatin or any of accessories;
18. A prior malignancy other than NSCLC within 5 years before randomization，except carcinoma in situ of the cervix or basal cell carcinoma or squamous cell carcinoma of skin cancer with adequately treated, localized prostate cancer or ductal carcinoma in situ after radical resection.

Primary outcomes:
measure: Intracranial Progression-Free Survival(iPFS)
timeFrame: up to 24 month
Secondary outcomes:
measure: Intracranial Objective Response Rate (iORR)
timeFrame: up to 24 month
measure: Objective Response Rate (ORR)
timeFrame: up to 24 month
measure: Progression-Free Survival (PFS)
timeFrame: up to 24 month
measure: Overall Survival (OS)
timeFrame: up to 24 month
measure: Duration of Response (DOR)
timeFrame: up to 24 month
measure: Quality of Life (QoL)
timeFrame: up to 24 month
measure: Adverse events (AEs)/ Serious adverse event (SAE)
timeFrame: up to 24 month
measure: Simple Mental State Scale of Intelligence (MMSE)
timeFrame: up to 24 month
measure: Revised Hopkins Vocabulary Learning Test Scale (HVLT-R)
timeFrame: up to 24 month
Other outcomes:
Locations:
Study officials:
affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences
name: Wu Yi Long, PhD
role: PRINCIPAL_INVESTIGATOR
References: