Camrelizumab Combined With SRT/WBRT and Chemotherapy in Patients With Brain Metastases of Driven Gene-negative NSCLC
Phase 3
- Conditions
- Non-Small-Cell Lung Cancer
- Interventions
- Registration Number
- NCT04768075
- Lead Sponsor
- Guangdong Association of Clinical Trials
- 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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 200
Inclusion Criteria
- 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;
Exclusion Criteria
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Camrelizumab group Albumin paclitaxel 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. placebo group Albumin paclitaxel 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. placebo group Placebo 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. placebo group Paclitaxel 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. Camrelizumab group Camrelizumab 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. Camrelizumab group Cisplatin 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. Camrelizumab group Carboplatin 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. Camrelizumab group Pemetrexed 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. Camrelizumab group Paclitaxel 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. placebo group Cisplatin 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. placebo group Carboplatin 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. placebo group Pemetrexed 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.
- Primary Outcome Measures
Name Time Method Intracranial Progression-Free Survival(iPFS) 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
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) up to 24 month OS was defined as the time from randomization to death due to any cause.
Duration of Response (DOR) up to 24 month DOR was defined as the time from first documented evidence of a CR or PR until PD or death
Adverse events (AEs)/ Serious adverse event (SAE) up to 24 month All adverse event/Serious adverse event that occurred during the study period according to CTCAE v 5.0
Simple Mental State Scale of Intelligence (MMSE) up to 24 month Assessment of cognitive function based on the MMSE ,the values from 0 to 30, higher scores mean a better outcome.
Revised Hopkins Vocabulary Learning Test Scale (HVLT-R) up to 24 month Assessment of cognitive function based on the HVLT-R，higher scores mean a better outcome.
Progression-Free Survival (PFS) up to 24 month PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first.
Quality of Life (QoL) up to 24 month Evaluate according to the quality of life score V3.0，higher scores mean a better outcome.
Intracranial Objective Response Rate (iORR) up to 24 month iORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response(PR: ≥30% decrease in the sum of diameters of target lesions) in brain lesion per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Objective Response Rate (ORR) up to 24 month ORR was defined as the percentage of participants in the analysis population who had a CR or a PR.