Prediction of Response to PD-L1 Inhibitor After Chemoradiotherapy in Limited-Stage Small-Cell Lung Cancer Using Multi-omics-based Liquid Biopsy

NCT06869239 | Recruiting

• 1 other identifier: BRWEP2024W032150110
• Study Type: observational
• Target: 65
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to explore the efficacy and safety of immunotherapy (PD-L1 inhibitor) maintenance following high-dose hyperfractionated simultaneous integrated boost radiotherapy concurrent chemotherapy in patients with limited-stage small cell lung cancer (LS-SCLC). This study is a prospective observational study. Additionally, liquid biopsy technology will be employed to identify biomarkers that can predict the efficacy of PD-L1 inhibitor after chemoradiotherapy in LS-SCLC.

Conditions

Limited-stage Small Cell Lung Cancer (LS-SCLC)

Keywords

LS-SCLC; immunotherapy; liquid biopsy; high-dose radiotherapy

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  The time from enrollment to disease progression or death due to any cause, whichever occurs first.

  From enrollment to disease progression or death due to any cause, whichever occurs first, assessed up to 3 years.

Secondary Outcomes (4)

• Overall survival

  The time from enrollment to death due to any cause, assessed up to 3 years.

• Objective response rate

  Up to 3 years

• Disease control rate

  Up to 3 years

• Incidence and severity of adverse events

  From enrollment to 30 days after the end of study treatment.

Other Outcomes (1)

• Blood biomarker analysis

  Up to 3 years

Study Arms (1)

PD-L1 inhibitor after chemoradiotherapy

PD-L1 inhibitor maintenance following high-dose hyperfractionated simultaneous integrated boost radiotherapy concurrent chemotherapy in patients with limited-stage small cell lung cancer

Drug: Etoposide + cisplatin/carboplatin; Radiation: Thoracic radiotherapy; Radiation: Prophylactic cranial irradiation (PCI); Drug: PD-L1 inhibitor

Interventions

Etoposide + cisplatin/carboplatin DRUG

Four courses of intravenous cisplatin (75 mg/m² of body surface area on day 1 or divided into 3 days of each cycle) or carboplatin (area under the curve of 5 mg/mL per min on day 1 of each cycle) and intravenous etoposide (100 mg/m² of body surface area on days 1-3) every 3 weeks

PD-L1 inhibitor after chemoradiotherapy

Thoracic radiotherapy RADIATION

High-dose, accelerated, hyperfractionated, twice-daily thoracic radiotherapy (54 Gy in 30 fractions) concurrent with chemotherapy initiated at the beginning of cycles 1-3

PD-L1 inhibitor after chemoradiotherapy

Prophylactic cranial irradiation (PCI) RADIATION

PCI (25Gy in 10 fractions, once daily over two weeks) 3-4 weeks post-chemoradiotherapy for patients achieving PR or CR

PD-L1 inhibitor after chemoradiotherapy

PD-L1 inhibitor DRUG

Maintenance therapy with PD-L1 inhibitors (Durvalumab 1500 mg Q4W or Atezolizumab 1200 mg Q3W or Sugemalimab 1200 mg Q3W or Adebrelimab 1200 mg Q3W) post-PCI until disease progression, death, or intolerable toxicity, up to 2 years

PD-L1 inhibitor after chemoradiotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

LS-SCLC with PD-L1 inhibitor after Chemoradiotherapy

You may qualify if:

• \. Age 18-75 years, male or female;
• \. Histologically or cytologically confirmed limited-stage small cell lung cancer (LS-SCLC) (AJCC, 8th edition);
• \. No more than 2 cycles of chemotherapy or no previous systemic therapy;
• \. ECOG PS 0-1;
• \. Measurable disease, as defined by RECIST v1.1 (tumor lesions long axis≥10mm, lymph nodes short axis ≥15mm);
• \. Life expectancy ≥3 months;
• \. Adequate pulmonary function;
• \. Adequate hematologic and end-organ function, defined by the following criteria:
• Hematology
• Hemoglobin (HGB) ≥90 g/L;
• Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L;
• Platelet count (PLT) ≥ 100 x 10\^9/L;
• White blood cell count (WBC) ≥ 3.0 x 10\^9/L;
• Serum chemistry
• Serum albumin (ALB) ≥ 30 g/L;

You may not qualify if:

• \. Histological mixture of SCLC and NSCLC components;
• \. Extensive-stage SCLC;
• \. Patients with a history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation, or those planned for transplantation;
• \. Treatment with immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within 14 days prior to the first dose of PD-L1 inhibitor, except for intranasal and inhaled corticosteroids or low-dose systemic steroids (i.e., ≤10 mg/day prednisolone or equivalent);
• \. History of hypersensitivity to etoposide, cisplatin, PD-L1 antibody, or excipients in the formulation; or history of severe allergic reactions to other monoclonal antibodies;
• \. Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during study treatment;
• \. Active or history of autoimmune disease or immune deficiency (including but not limited to autoimmune hepatitis, interstitial pneumonitis, uveitis, enteritis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism);
• Note:
• Patients with vitiligo or alopecia are eligible for this study;
• Patients with stable hypothyroidism undergoing hormone replacement therapy (e.g., Hashimoto's syndrome) are eligible for this study;
• \. Poorly controlled asthma despite systemic treatment, such as bronchodilators; Note: Patients with complete remission of asthma during childhood and no need for any intervention in adulthood can be allowed;
• \. Urinalysis shows proteinuria ≥ ++ or confirmed 24-hour urine protein ≥ 1.0g;
• \. Malignancies other than LS-SCLC, with the following exceptions:
• Adequately treated basal or squamous cell skin cancer or carcinoma in situ of the cervix;
• Malignancy that has been treated with curative intent, with no known active disease for ≥5 years prior to the first dose of the study treatment, and with a low potential risk of recurrence;

Sponsors & Collaborators

• Peking University Cancer Hospital & Institute: lead

Study Sites (1)

Peking University Cancer Hospital & Institute

Beijing, Beijing Municipality, 100142, China

RECRUITING

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

Etoposide; Cisplatin; Carboplatin; Immune Checkpoint Inhibitors

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Central Study Contacts

Anhui Shi

CONTACT

8601088196087; anhuidoctor@163.com

Jiayi Yu

CONTACT

8601088196087

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2025
• First Posted: March 11, 2025
• Study Start: February 25, 2025
• Primary Completion (Estimated): January 3, 2027
• Study Completion (Estimated): January 3, 2028
• Last Updated: March 11, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Available after publication
• Access Criteria: Request by email to PI

Locations

CN (1)