CAP-BRAIN: Camrelizumab With AC in Patients With Brain Metastases of Driven Gene-negative,NSCLC

Sponsor

Sun Yat-sen University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04211090

Collaborator

Jiangsu HengRui Medicine Co., Ltd. (Industry)

Enrollment

Location

Arm

Anticipated Duration (Months)

1.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary hypothesis is that camrelizumab in combination with pemetrexed/ carboplatin will present a better efficacy for treatment of first line metastatic non-squamous non-small cell lung cancer and minimize the risk of toxicity

Condition or Disease	Intervention/Treatment	Phase
Non-squamous Non-small-cell Lung Cancer Brain Metastases	Drug: Camrelizumab Drug: Pemetrexed Drug: Carboplatin	Phase 2

Detailed Description

This is a prospective, open-label, phase Ⅱ studyto evaluate the efficacy and safetyof camrelizumab combined with pemetrexed/ carboplatin in participants with brain metastases ofnon-squamous non-small cell lung cancer.Paticipant was confirmed without EGFR activating mutation or ALK fusion, and received no prior systemic therapy.Patients would receive camrelizumab in combination with pemetrexed/ carboplatin for 4 cycles，followed by camrelizumab and pemetrexed as maitenance treatment until progression, camrelizumab will be administered no more than 24 months. PD-L1 expression assessed with 22C3 pharmDx assay will be used as a stratification factor.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

64 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

patients with brain metastases of driven gene-negative, non-squamous non-small cell lung cancerpatients with brain metastases of driven gene-negative, non-squamous non-small cell lung cancer

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Study to Evaluate Camrelizumab With Pemetrexed / Carboplatin in Patients With Brain Metastases of Driven Gene-negative, Non-squamous Non-small Cell Lung Cancer

Anticipated Study Start Date :

Jan 15, 2020

Anticipated Primary Completion Date :

Jan 15, 2022

Anticipated Study Completion Date :

Jul 15, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Camrelizumab with pemetrexed / carboplatin Camrelizumab with pemetrexed / carboplatin in patients with brain metastases of driven gene-negative, non-squamous non-small cell lung cancer	Drug: Camrelizumab Camrelizumab with pemetrexed / carboplatin in patients with brain metastases of driven gene-negative, non-squamous non-small cell lung cancer, Participants receive a 3-week cycle (Q3W) treatment，Treatment continued until disease progression or unacceptable toxicity or death or, for the immunotherapy regimens Drug: Pemetrexed Camrelizumab with pemetrexed / carboplatin in patients with brain metastases of driven gene-negative, non-squamous non-small cell lung cancer, Participants receive a 3-week cycle (Q3W) treatment，Treatment continued until disease progression or unacceptable toxicity or death or, for the immunotherapy regimens Drug: Carboplatin Camrelizumab with pemetrexed / carboplatin in patients with brain metastases of driven gene-negative, non-squamous non-small cell lung cancer, Participants receive a 3-week cycle (Q3W) treatment，Treatment continued until disease progression or unacceptable toxicity or death or, for the immunotherapy regimens

Arm

Intervention/Treatment

Experimental: Camrelizumab with pemetrexed / carboplatin

Camrelizumab with pemetrexed / carboplatin in patients with brain metastases of driven gene-negative, non-squamous non-small cell lung cancer

Drug: Camrelizumab

Camrelizumab with pemetrexed / carboplatin in patients with brain metastases of driven gene-negative, non-squamous non-small cell lung cancer, Participants receive a 3-week cycle (Q3W) treatment，Treatment continued until disease progression or unacceptable toxicity or death or, for the immunotherapy regimens

Drug: Pemetrexed

Drug: Carboplatin

Outcome Measures

Primary Outcome Measures

Intracranial Objective Response Rate (iORR) [3.5year]
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

Secondary Outcome Measures

Intracranial Progression-Free Survival(iPFS) [3.5year]
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
Objective Response Rate (ORR) [3.5year]
ORR 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) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Progression-free Survival (PFS) [3.5year]
Progression-free survival is defined as the duration from date of enrollment to the first occurrence of progression of disease or death from any cause
Incidence of Adverse Events (AEs) [3.5year]
Incidence of Adverse Events (AEs) in the treatment of Camrelizumab combined with pemetrexed / carboplatin for patients with brain metastasis according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histological or cytological diagnosis of non-squamous non-small cell lung cancer（NSCLC）
Subjects with asymptomatic brain metastasis or the symptoms of intracranial hypertension were relieved after dehydration treatment, and kept clinically stable for ≥ 2 weeks. Subjects who need hormone dehydration treatment, hormone therapy should be stopped 3 days before the first dose of the investigational drugs;
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 using RECIST 1.1 criteria.,
Subjects have not received prior systemic treatment for metastatic NSCLC.
Tumor tissue biomarkers examination should be complied with: 1) Subjects should not have a previously detected sensitizing EGFR mutation or ALK fusion oncogene. 2) Subjects should have sufficient tissue samples for PD-L1 detection (IHC,DAKO 22C3 pharmDx).
age:18~75years
ECOG performance status of 0 or 1.
Life expectancy ≥ 3 months.
Blood routine examination should be complied with (No blood transfusion, no use of hematopoietic factors and no use of drugs for correction within 7 days):
ANC ≥ 1.5×109/L；
PLT ≥ 100×109/L；
HB ≥ 90 g/L；
Has adequate organ function,Biochemical tests must meet the following criteria:

TBIL ≤ 1.5ULN； ALT、AST≤ 2.5 ULN (If abnormal liver function is caused by liver metastasis, ALT、AST< 5ULN; Cr≤1.5ULN，endogenous creatinine clearance rate≥60ml/min(Cockcroft-Gault formula);

Blood coagulation must meet the following criteria: INR≤1.5 and APTT≤1.5 ULN；
Women of childbearing age must undergo a serological pregnancy test within 7 days before the first dose with negative results and willing to use a medically approved and effective contraceptive method (e.g. intrauterine device, contraceptive pill or condom) during the study and within two months after the last dose. For male subjects whose partners are women of childbearing age, they should be sterilized surgically or agree to use effective contraceptive methods during the study and within two months after the last dose.
Subjects should be able to follow the research and follow-up procedures;
Subjects should be voluntarily participate in clinical studies and informed consent should be signed.

Exclusion Criteria:

Subjects with predominantly squamous cell histology NSCLC, or SCLC.
brain metastases with hemorrhage;
Participated in other clinical trials, or finish other clinical trials within 4 weeks.
Subjects have received prior systemic treatment for metastatic NSCLC；
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;
systemic glucocorticoid therapy or any other form of immunosuppressive therapy is being given within 7 days before the first administration of the study; physiological doses of glucocorticoids are allowed (prednisone or equivalent for ≤ 10 mg/ days);
within 1 year before the first administration, there was a history of non-infectious pneumonia or interstitial lung disease requiring glucocorticoid treatment;
Subjects with congenital or acquired immunodeficiency such as HIV infection, active hepatitis B (HBV DNA ≥ 200 IU/ml), hepatitis C (hepatitis C antibody is positive).
Women who are pregnant or lactating
Known history of hypersensitivity to any components of the Camrelizumab formulation，or other monoclonal antibody.
Known history of hypersensitivity to pemetrexed, carboplatin or any of its excipients;
A prior malignancy other than NSCLC, except carcinoma in situ of the cervix or non-melanoma skin cancer, adequately treated low grade [Gleason score <6] localized prostate cancer, unless that prior malignancy was diagnosed and definitively treated at least 5 years previously with no subsequent evidence of recurrence-