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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 14
- 主要终点
- Intracranial Progression-Free Survival(iPFS)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histological or cytological diagnosis of non-small cell lung cancer（NSCLC）;
- •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;
- •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;
- •Has confirmation that epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK)-directed therapy is not indicated;
- •Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status;
- •Has adequate organ function;
- •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;
- •Subjects should be able to follow the research and follow-up procedures;
- •Subjects should be voluntarily participating in clinical studies and informed consent should be signed;
排除标准
- •Brain metastases with hemorrhage；
- •Meningeal involvement with metastatic carcinoma;
- •Subjects with ROS1 mutation, RET fusion positive, BRAF V600E mutation, NTRK fusion positive;
- •Participated in other clinical trials, or finish other clinical trials within 4 weeks;
- •Subject was received irradiation of brain;
- •Subjects have received solid organ or blood system transplantation;
- •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;
- •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);
- •Within 1 year before the first dose, there was a history of non-infectious pneumonia or interstitial lung disease requiring glucocorticoid treatment;
- •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;
- •Has known history of Human Immunodeficiency Virus (HIV)；
- •Untreated active hepatitis B；
- •Subjects have active hepatitis B；
- •Subjects have severe infections within 4 weeks of the first dose of study treatment；
- •Subjects with clinically significant bleeding symptoms or with obvious bleeding tendency in the first month;
- •Women who are pregnant or lactating；
- •Has known allergy to Camrelizumab, or pemetrexed, or paclitaxel, or albumin paclitaxel, or carboplatin, or cisplatin or any of accessories;
- •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.
研究组 & 干预措施
Camrelizumab group
subject will receive Camrelizumab intravenously(IV) PLUS pemetrexed or paclitaxel or albumin paclitaxel PLUS cisplatin or carboplatin AUC 5 on Day 1 of each 3-week cycle(Q3W) for 4-6 cycles followed by Camrelizumab ± pemetrexed IV Q3W until progression (up to approximately 2 years).
Whether the subject accepts intracranial radiotherapy will be decided by investigators according to the guidelines and the conditions of the subjects.
干预措施: Camrelizumab (Drug)
Camrelizumab group
subject will receive Camrelizumab intravenously(IV) PLUS pemetrexed or paclitaxel or albumin paclitaxel PLUS cisplatin or carboplatin AUC 5 on Day 1 of each 3-week cycle(Q3W) for 4-6 cycles followed by Camrelizumab ± pemetrexed IV Q3W until progression (up to approximately 2 years).
Whether the subject accepts intracranial radiotherapy will be decided by investigators according to the guidelines and the conditions of the subjects.
干预措施: Cisplatin (Drug)
Camrelizumab group
subject will receive Camrelizumab intravenously(IV) PLUS pemetrexed or paclitaxel or albumin paclitaxel PLUS cisplatin or carboplatin AUC 5 on Day 1 of each 3-week cycle(Q3W) for 4-6 cycles followed by Camrelizumab ± pemetrexed IV Q3W until progression (up to approximately 2 years).
Whether the subject accepts intracranial radiotherapy will be decided by investigators according to the guidelines and the conditions of the subjects.
干预措施: Paclitaxel (Drug)
placebo group
subject will receive placebo intravenously (IV) PLUS pemetrexed or paclitaxel or albumin paclitaxel PLUS cisplatin or carboplatin AUC 5 on Day 1 of each 3-week cycle(Q3W) for 4-6 cycles followed by placebo ± pemetrexed IV Q3W until progression (up to approximately 2 years).
Whether the subject accepts intracranial radiotherapy will be decided by investigators according to the guidelines and the conditions of the subjects.
干预措施: Cisplatin (Drug)
placebo group
subject will receive placebo intravenously (IV) PLUS pemetrexed or paclitaxel or albumin paclitaxel PLUS cisplatin or carboplatin AUC 5 on Day 1 of each 3-week cycle(Q3W) for 4-6 cycles followed by placebo ± pemetrexed IV Q3W until progression (up to approximately 2 years).
Whether the subject accepts intracranial radiotherapy will be decided by investigators according to the guidelines and the conditions of the subjects.
干预措施: Carboplatin (Drug)
Camrelizumab group
subject will receive Camrelizumab intravenously(IV) PLUS pemetrexed or paclitaxel or albumin paclitaxel PLUS cisplatin or carboplatin AUC 5 on Day 1 of each 3-week cycle(Q3W) for 4-6 cycles followed by Camrelizumab ± pemetrexed IV Q3W until progression (up to approximately 2 years).
Whether the subject accepts intracranial radiotherapy will be decided by investigators according to the guidelines and the conditions of the subjects.
干预措施: Carboplatin (Drug)
Camrelizumab group
subject will receive Camrelizumab intravenously(IV) PLUS pemetrexed or paclitaxel or albumin paclitaxel PLUS cisplatin or carboplatin AUC 5 on Day 1 of each 3-week cycle(Q3W) for 4-6 cycles followed by Camrelizumab ± pemetrexed IV Q3W until progression (up to approximately 2 years).
Whether the subject accepts intracranial radiotherapy will be decided by investigators according to the guidelines and the conditions of the subjects.
干预措施: Pemetrexed (Drug)
placebo group
subject will receive placebo intravenously (IV) PLUS pemetrexed or paclitaxel or albumin paclitaxel PLUS cisplatin or carboplatin AUC 5 on Day 1 of each 3-week cycle(Q3W) for 4-6 cycles followed by placebo ± pemetrexed IV Q3W until progression (up to approximately 2 years).
Whether the subject accepts intracranial radiotherapy will be decided by investigators according to the guidelines and the conditions of the subjects.
干预措施: Pemetrexed (Drug)
placebo group
subject will receive placebo intravenously (IV) PLUS pemetrexed or paclitaxel or albumin paclitaxel PLUS cisplatin or carboplatin AUC 5 on Day 1 of each 3-week cycle(Q3W) for 4-6 cycles followed by placebo ± pemetrexed IV Q3W until progression (up to approximately 2 years).
Whether the subject accepts intracranial radiotherapy will be decided by investigators according to the guidelines and the conditions of the subjects.
干预措施: Placebo (Drug)
placebo group
subject will receive placebo intravenously (IV) PLUS pemetrexed or paclitaxel or albumin paclitaxel PLUS cisplatin or carboplatin AUC 5 on Day 1 of each 3-week cycle(Q3W) for 4-6 cycles followed by placebo ± pemetrexed IV Q3W until progression (up to approximately 2 years).
Whether the subject accepts intracranial radiotherapy will be decided by investigators according to the guidelines and the conditions of the subjects.
干预措施: Albumin paclitaxel (Drug)
Camrelizumab group
subject will receive Camrelizumab intravenously(IV) PLUS pemetrexed or paclitaxel or albumin paclitaxel PLUS cisplatin or carboplatin AUC 5 on Day 1 of each 3-week cycle(Q3W) for 4-6 cycles followed by Camrelizumab ± pemetrexed IV Q3W until progression (up to approximately 2 years).
Whether the subject accepts intracranial radiotherapy will be decided by investigators according to the guidelines and the conditions of the subjects.
干预措施: Albumin paclitaxel (Drug)
placebo group
subject will receive placebo intravenously (IV) PLUS pemetrexed or paclitaxel or albumin paclitaxel PLUS cisplatin or carboplatin AUC 5 on Day 1 of each 3-week cycle(Q3W) for 4-6 cycles followed by placebo ± pemetrexed IV Q3W until progression (up to approximately 2 years).
Whether the subject accepts intracranial radiotherapy will be decided by investigators according to the guidelines and the conditions of the subjects.
干预措施: Paclitaxel (Drug)
结局指标
主要结局
Intracranial Progression-Free Survival(iPFS)
时间窗: up to 24 month
Intracranial Progression-free survival is defined as the duration from date of enrollment to the first occurrence of progression in brain metastasis disease or death from any cause or switch therapy
次要结局
- Overall Survival (OS)(up to 24 month)
- Duration of Response (DOR)(up to 24 month)
- Adverse events (AEs)/ Serious adverse event (SAE)(up to 24 month)
- Simple Mental State Scale of Intelligence (MMSE)(up to 24 month)
- Revised Hopkins Vocabulary Learning Test Scale (HVLT-R)(up to 24 month)
- Quality of Life (QoL)(up to 24 month)
- Intracranial Objective Response Rate (iORR)(up to 24 month)
- Progression-Free Survival (PFS)(up to 24 month)
- Objective Response Rate (ORR)(up to 24 month)