Clinical trial NCT05933863: Molecular Subtyping of Extensive Stage Small Cell Lung Cancer and Relevent Clinical Significance
Official title: Molecular Subtyping of Extensive Stage Small Cell Lung Cancer and Relevent Clinical Significance
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: SCLC,Extensive Stage
Lead sponsor: Peking University Cancer Hospital & Institute
Sponsor class: OTHER
First posted: 2023-07-06
Enrollment: 168
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This study includes adults (18-100 years) with untreated advanced SCLC. Eligible patients have an ECOG score of 0\~2, an expected survival \>3 months, and can provide tumor biopsy samples for transcripsome testing. They must have received first-line chemotherapy or chemotherapy combined with a PD-L1 inhibitor.

Participants are divided into two arms: Chemotherapy (80-100 cases) and Immunotherapy+chemotherapy (80-100 cases). Exclusion criteria include intolerance to chemotherapy, inability to provide tumor tissue samples, presence/history of other malignant tumors, and other reasons deeming them unfit for the study.

Brief summary: To validate the predictive value of transcriptome-based molecular subtyping of extensive stage small cell lung cancer (SCLC) for the efficacy of programmed death-1(PD-1)/programmed death-ligand1(PD-L1) inhibitor in the first line setting; to explore the differences of immune microenvironment between different SCLC subtypes to reveal the mechanisms of immunotherapy resistance of SCLC

Detailed description: This retrospective observational study examines the predictive value of transcriptome-based molecular subtyping of extensive stage SCLC for PD-1/PD-L1 inhibitor efficacy and explores immune microenvironment differences between subtypes to uncover immunotherapy resistance mechanisms. Patients with extensive stage SCLC receiving first-line standard treatment are enrolled, and baseline tumor tissue and peripheral blood samples are collected for transcriptome sequencing and immunohistochemistry (IHC). Based on results, patients are classified into four molecular subtypes, and treatment efficacy and safety are recorded. The study compares the efficacy between SCLC subtypes to determine if molecular typing predicts immunotherapy efficacy and investigates immune microenvironment differences between subtypes to uncover resistance mechanisms. Treatment regimens follow first-line extensive stage SCLC guidelines, including cisplatin+etoposide or carboplatin+etoposide and PD-(L)1 inhibitors, with options determined by the supervising physician.

Eligibility criteria: Inclusion Criteria:

* The enrolled subjects shall meet all the following conditions at the same time.

  1. Male or female, aged 18 to 100 years
  2. Patients with untreated advanced small cell lung cancer clearly diagnosed by histopathology
  3. Be able to provide tumor biopsy tissue sample for molecular analysis
  4. Eastern Cooperative oncology Group (ECOG) score: 0\~2
  5. Expected survival of more than 3 months.
  6. Has at least 1 measurable or evaluable tumor lesion with a longest diameter ≥ 10 mm at baseline (in case of lymph nodes, a shortest diameter ≥ 15 mm is required) according to RECIST v1.1
  7. Received first-line chemotherapy or chemotherapy＋PD-(L)1 inhibitor and be able to provide complete treatment information and efficacy evaluation results.
  8. Voluntary signed informed consent and expected good compliance.

Exclusion Criteria:

* Those meeting any of the following conditions may not be included.

  1. Patient unable to tolerate chemotherapy.
  2. Patients unable to provide tumor tissue samples for testing
  3. Patients with other malignant tumors or a history of other malignant tumors
  4. Patients have any other reason to be unfit to participate in this study.

Primary outcomes:
measure: Progression-free survival
timeFrame: 2022.4.1-2023.12.31
Secondary outcomes:
measure: Overall survival
timeFrame: 2022.4.10-2024.12.31
measure: Objective response rate
timeFrame: 2022.4.10-2023.12.31
measure: molecular subtyping and tumor microenvironment biomarkers
timeFrame: 2022.4.10-2023.12.31
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University Cancer Hospital & Institute
state: Beijing
Study officials:
affiliation: Peking University Cancer Hospital & Institute
name: Minglei Zhuo, Physician
role: PRINCIPAL_INVESTIGATOR
References: