Non-Small-Cell Lung Cancer
Conditions
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.
Interventions
DRUGCamrelizumab
Camrelizumab is a humanized anti-PD1 IgG4 monoclonal antibody
DRUGPlacebo
IV infusion Simulator of Camrelizumab
DRUGCisplatin
IV infusion
DRUGCarboplatin
IV infusion
DRUGPemetrexed
IV infusion
DRUGPaclitaxel
IV infusion
DRUGAlbumin paclitaxel
IV infusion
Sponsors
Guangdong Association of Clinical Trials
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Intracranial Progression-Free Survival(iPFS) | up to 24 months | 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 |
| Progression-Free Survival (PFS) | up to 24 months | PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Intracranial Objective Response Rate (iORR) | up to 24 months | 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 months | ORR was defined as the percentage of participants in the analysis population who had a CR or a PR. |
| Intracranial Duration of Response (iDOR) | up to 24 months | iDOR was defined as the time from first documented evidence of a CR or PR until PD or death |
| Overall Survival (OS) | up to death | OS was defined as the time from randomization to death due to any cause. |
| Duration of Response (DOR) | up to 24 months | 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 months | All adverse event/Serious adverse event that occurred during the study period according to CTCAE v 5.0 |
| Mini-Mental State Examination (MMSE) | Assessed at baseline and at each scheduled tumor imaging assessment (every 6 weeks for the first 48 weeks, then every 12 weeks thereafter) up to 24 months | Assessment of cognitive function using the Mini-Mental State Examination (MMSE). The MMSE evaluates orientation, registration, attention and calculation, recall, and language. Total scores range from 0 to 30, with higher scores indicating better cognitive function. |
| Hopkins Verbal Learning Test - Revised (HVLT-R) | Assessed at baseline and at each scheduled tumor imaging assessment (every 6 weeks for the first 48 weeks, then every 12 weeks thereafter) up to 24 months | Assessment of verbal learning and memory using the Hopkins Verbal Learning Test - Revised (HVLT-R). The HVLT-R consists of three learning trials of a 12-word list, a delayed recall trial, and a delayed recognition trial. Total recall score (trials 1-3) ranges from 0 to 36, delayed recall score from 0 to 12, and recognition discrimination index from -12 to 12. Higher scores indicate better verbal learning and memory function. |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORWu Yi Long, PhD
Guangdong Lung Cancer Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences
Outcome results
None listed