PICARES: PD-1 Inhibitors Consolidation in Extensive-stage Small Cell Lung Cancer

Sponsor

Chinese Academy of Medical Sciences (Other)

Overall Status

Unknown status

CT.gov ID

NCT03971214

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The prognosis of extensive-stage small cell lung cancer is still very poor, even for those who received platinum-based chemotherapy and chest radiotherapy. 2-year survival rate of these patients is only about 10%. Therefore, this study aims to explore a comprehensive treatments with low toxicity to further improve the efficacy for these paitents with PD-1 inhibitor.

Condition or Disease	Intervention/Treatment	Phase
Extensive-stage Small Cell Lung Cancer Radiotherapy Immunotherapy	Drug: PD-1 inhibitor JS-001	Phase 1

Detailed Description

The study is a prospective pilot trial. The purpose of this study is to evaluate the safety and efficacy of PD-1 inhibitor consolidation in extensive-stage small cell lung cancer paitents who received standard first-line chemotherapy and chest radiotherapy ± SABR for metastasis disease.

The primary endpoint is the safety and objective response rate of treatment. The secondary objectives are progression free survival(PFS), overall survial. The exploratory end point includes the correlation of PD-1 expression on the tumor tissue, and the TMB, Immune Repertoire sequencing derived from the tumor tissue and the blood sample with the efficacy of treatent. The plan for collection of tumor tissue and blood at baseline at different stages during or after treatment was defined in the protocol.

The PICCARE-trial has been designed by National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, and the hypothesis is PD-1 inhibitor consolidation was safe and effective in the treatment of extensive-stage SCLC after sandard first-line chemotherapy and radiotherapy.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

6 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Pilot Study on PD-1 Inhibitors Consolidation After Standard First-line Chemotherapy and Radiotherapy in Extensive-stage Small Cell Lung Cancer

Anticipated Study Start Date :

Jun 1, 2019

Anticipated Primary Completion Date :

Jun 1, 2020

Anticipated Study Completion Date :

Jun 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PD-1 inhibitor JS-001 consolidation for SCLC The extensive-stage SCLC patients will receive PD-1 inhibitor JS-001 treatment after standard first-line chemotherapy, chest radiotherapy ± SABR for metastasis disease, and propylactic cranial irradiation untill disease progression or death.	Drug: PD-1 inhibitor JS-001 The extensive-stage SCLC patients will receive PD-1 inhibitor treatment after standard first-line chemotherapy, chest radiotherapy ± SABR for metastasis disease, and propylactic cranial irradiation untill disease progression or death. Other Names: chemotherapy radiotherapy SABR propylactic cranial irradiation

Arm

Intervention/Treatment

Experimental: PD-1 inhibitor JS-001 consolidation for SCLC

The extensive-stage SCLC patients will receive PD-1 inhibitor JS-001 treatment after standard first-line chemotherapy, chest radiotherapy ± SABR for metastasis disease, and propylactic cranial irradiation untill disease progression or death.

Drug: PD-1 inhibitor JS-001

The extensive-stage SCLC patients will receive PD-1 inhibitor treatment after standard first-line chemotherapy, chest radiotherapy ± SABR for metastasis disease, and propylactic cranial irradiation untill disease progression or death.

Other Names:

chemotherapy

radiotherapy

SABR

propylactic cranial irradiation

Outcome Measures

Primary Outcome Measures

Adverse events [At least 1 year following the conclusion of immunotherapy]
The incidence and severity of adverse events related to treatments
Objective remission rate [24 weeks following the conclusion of immunotherapy]
Objective remission rate (ORR): refers to the proportion of subjects in the analyzed population who achieved complete remission (CR) or partial remission (PR); according to the tumor immunotherapy efficacy evaluation (irRC) and RECIST criteria (v1.1) by the evaluation of investigator.

Secondary Outcome Measures

Pharmacodynamic indicators [During and 6 weeks after the treatment of immunotherapy]
Pharmacodynamic indicators，such as the detection of PD-1 receptor occupancy in the blood
Continuous remission time (DOR) [At least 1 year following the conclusion of immunotherapy]
DOR was defined as time since onset of CR or PR to relapse or death due to underlying cancer, whichever is earlier
Disease Control Rate (DCR) [At least 1 year following the conclusion of immunotherapy]
The percentage of patients who have achieved complete response, partial response and stable disease to the therapeutic intervention
Time to response (TTR) [24 weeks following the conclusion of immunotherapy]
The time from the start of treatment to the first objective tumor response
Progression-free survival (PFS) [At least 1 year following the conclusion of immunotherapy]
The length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse
Overall survival (OS) [At least 1 year following the conclusion of immunotherapy]
The time from treatment to death from any cause

Other Outcome Measures

Exploratory end point including biomarkers [At least 1 year following the conclusion of immunotherapy]
To explore the correlation of PD-L1 expression in tumor tissue , TCR, ctDNA in peripheral blood and efficacy

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Sign written informed consent;
With extensive small cell lung cancer;
Previously received first-line standard chemotherapy, with treatment response of CR or PR;
Can provide at least 5-8 pathological tissue specimens (for detecting PD-L1 expression and infiltrating lymphocytes)
Can tolerate the radiotherapy process;
Weight ≥ 40kg;
Life expectancy ≥ 12 weeks;
With the Eastern Cancer Cooperative Group (ECOG) score 0-1;
The interval from the previous chemotherapy is more than 4 weeks, the grade of all adverse events caused by previous treatment have been reduced to grade 1 or less evaluated by CTCAE 4.03;
Before the administration of the study drug, systemic drugs (such as corticosteroids) applied at an immunosuppressive dose level (prednisone > 10 mg/d or equivalent) must have been discontinued for at least 2 weeks;
Major surgery requiring general anesthesia must have been completed for at least 4 weeks before administration of the study drug. Surgery requiring local anesthesia/epidural anesthesia must have been completed for at least 72 hours before administration of the study drug, and the subject must have recovered. Skin biopsy with only local anesthesia has been completed for at least 1 hour before administration of the study drug.
Other criteria including the laboratory values meets the requirements specified in the protocol.

Exclusion Criteria:

Subjects with central nervous system (CNS) metastases;
The subject has cancerous meningitis;
Subjects with active, known or suspected autoimmune diseases ;
Previously treated with anti-PD-1 antibody, anti-PD-L1 antibody, anti-PD-L2 antibody or anti-CTLA-4 antibody (or any other antibody acting on the T cell stimulation or checkpoint pathway);
According to chest X-ray examination, sputum examination and clinical examination, it is determined that there is active tuberculosis (TB) infection now or before, even one year before;
A positive immunodeficiency virus (HIV) test or have acquired immunodeficiency syndrome (AIDS);
With comorbidity needs to be treated with an immunosuppressive drug;
Other research drugs were administrated 28 days prior to the start of study drug or although they were more than 28 days apart, still within the 5 half-life of previous study drugs;
Inoculated with any anti-infective vaccine (such as influenza vaccine, varicella vaccine, etc.) within 4 weeks before starting the study drug;
In the condition of pregnant or breastfeeding;
Inability to tolerate venous puncture and/or venous access;
Any other medical, psychotic, and/or social problems determined by the investigator;
Subject has interstitial lung disease;
Use any Chinese medicine with anti-tumor activity within 2 weeks before starting of the study drug;
Monoclonal antibodies have been used in the past 3 months, except for topical use;
Subjects who have previously had other malignancies (excluding non-melanoma skin cancer and the following carcinomas in situ: bladder, stomach, colon, endometrium, cervix/dysplasia, melanoma or breast cancer) are not allowed to participate in the study. Unless he/she has been cured at least 2 years prior to enrollment, and does not require additional treatment or other treatments during the study;
Subjects with chronic hepatitis B (hepatitis B surface antigen positive) or chronic hepatitis C (HCV antibody positive) blood screening positive;
Previously allergic to macromolecular protein preparations, or to any of the JS001 ingredients.