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

Immunotherapy Clinical Trial

— PICARES  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03971214
• Other study ID #: NCC1835
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: June 2019
• Est. completion date: June 2021

Study information

• Verified date: June 2019
• Source: Chinese Academy of Medical Sciences
• Contact: Wen-Yang Liu, MD
• Phone: 8613810753633
• Email: liuwenyang26[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 6
• Est. completion date: June 2021
• Est. primary completion date: June 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Extensive-stage Small Cell Lung Cancer
• Immunotherapy
• Lung Neoplasms
• Radiotherapy
• Small Cell Lung Carcinoma

Intervention

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.

Locations

Country	Name	City	State
China	Cancer Insititute and Hosiptal of Chinese Academy of Medical Sciences	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Chinese Academy of Medical Sciences

Country where clinical trial is conducted

China, 

References & Publications (33)

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* Note: There are 33 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Exploratory end point including biomarkers	To explore the correlation of PD-L1 expression in tumor tissue , TCR, ctDNA in peripheral blood and efficacy	At least 1 year following the conclusion of immunotherapy
Primary	Adverse events	The incidence and severity of adverse events related to treatments	At least 1 year following the conclusion of immunotherapy
Primary	Objective remission rate	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.	24 weeks following the conclusion of immunotherapy
Secondary	Pharmacodynamic indicators	Pharmacodynamic indicators,such as the detection of PD-1 receptor occupancy in the blood	During and 6 weeks after the treatment of immunotherapy
Secondary	Continuous remission time (DOR)	DOR was defined as time since onset of CR or PR to relapse or death due to underlying cancer, whichever is earlier	At least 1 year following the conclusion of immunotherapy
Secondary	Disease Control Rate (DCR)	The percentage of patients who have achieved complete response, partial response and stable disease to the therapeutic intervention	At least 1 year following the conclusion of immunotherapy
Secondary	Time to response (TTR)	The time from the start of treatment to the first objective tumor response	24 weeks following the conclusion of immunotherapy
Secondary	Progression-free survival (PFS)	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	At least 1 year following the conclusion of immunotherapy
Secondary	Overall survival (OS)	The time from treatment to death from any cause	At least 1 year following the conclusion of immunotherapy

External Links

•   Nivolumab (nivo) ± ipilimumab (ipi) in advanced small-cell lung cancer (SCLC): First report of a randomized expansion cohort from CheckMate 032