Selective Mediastinal Lymph Node Sampling Versus Systematic medIastinal Lymph Node Dissection After Neoadjuvant Chemoimmunotherapy for Non-small Cell Lung Cancer (SCIENCE Study)

Official title

Selective Mediastinal Lymph Node Sampling Versus Systematic medIastinal Lymph Node Dissection After Neoadjuvant Chemotherapy Combined With Immunotherapy for the Treatment of Clinical Stage IIA-IIIB (N2) Non-small Cell Lung Cancer

Overview

The SCIENCE trial is a multicenter, open-label, randomized, parallel, noninferiority investigator-initiated trial (IIT). This study aims to evaluate the prognostic differences between selective mediastinal lymph node sampling and systematic mediastinal lymph node dissection in patients with node-negative stage IIA to IIIB (N2) non-small-cell lung cancer (NSCLC) undergoing anatomical lobectomy following neoadjuvant chemoimmunotherapy.

Interventions

• Procedure selective mediastinal lymph node sampling
  Patients randomized to the investigational group will undergo an anatomical lobectomy. Subsequently, no further lymph node resection or dissection will be performed in regional stations confirmed negative for metastasis by preoperative or intraoperative pathological evaluation (including negative preoperative endobronchial ultrasound \[EBUS\]-guided biopsies and negative intraoperative frozen sections). Postoperatively, patients will receive 1 cycle of platinum-based doublet chemotherapy combine
• Procedure systematic mediastinal lymph node dissection
  Patients randomized to the control group will undergo a systematic mediastinal lymph node dissection following the completion of an anatomical lobectomy. A radical dissection and clearance of the mediastinal lymph nodes will be performed. For right-sided procedures, this encompasses the right upper paratracheal, right lower paratracheal, and subcarinal regions; for left-sided procedures, this encompasses the para-aortic, aortopulmonary window, left lower paratracheal, and subcarinal regions. Pos

Primary outcome measures

• 2-year event-free survival (EFS) rate [Time frame: Up to 2 years]

Secondary outcome measures (8)

• 2-year disease-free survival (DFS) rate [Time frame: Up to 2 years]
• 2-year overall survival (OS) rate [Time frame: Up to 2 years]
• Dynamic changes in absolute and relative peripheral blood lymphocyte counts [Time frame: Up to 2 years]
• Length of hospital stay [Time frame: Up to 30 days post-operation]
• time of operation [Time frame: Intraoperative]
• Intraoperative blood loss [Time frame: Intraoperative]
• postoperative recurrence rate (including the incidence of local recurrence and distant metastasis). [Time frame: Up to 2 years]
• Quality of life (QoL) scores at 6, 12, and 36 months postoperatively (assessed via the EORTC QLQ-C30). [Time frame: 6, 12, and 24 months post-operation]

Eligibility criteria

Inclusion criteria

• Voluntary participation with a signed written informed consent form.
• Aged ≥ 18 and < 75 years, of either gender.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Anticipated life expectancy of ≥ 12 months.
• Histologically or pathologically confirmed peripheral non-small cell lung cancer (NSCLC), with clinical tumor, node, metastasis(TNM) stage IIA-IIIB, which according to the International Association for the Study of Lung Cancer(IASLC) 9th edition, and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements.
• Absence of satellite nodules involving different lung lobes.
• No history of prior ipsilateral thoracotomy.
• Completion of neoadjuvant therapy prior to enrollment, consisting of a PD-1 inhibitor combined with platinum-based doublet chemotherapy.
• Adequate organ function.
• Cardiopulmonary function assessed by the investigator as meeting surgical standards, specifically: forced expiratory volume in one second (FEV1) > 1.0 L or diffusing capacity of the lung for carbon monoxide (DLCO) > 40% of the predicted value; and no other cardiopulmonary impairments that, in the investigator's judgment, would preclude surgery.
• Evaluation by a multidisciplinary team (MDT) or an evaluation committee\* confirming that R0 resection can be achieved via anatomical lobectomy.

• Evaluation Committee: Composed of multidisciplinary experts with at least 10 years of clinical experience. Each participant's eligibility is discussed and evaluated by at least two experts to reach a consensus; in the event of a disagreement, a third expert will be invited for assessment.

Exclusion criteria

• Anticipated inability to tolerate an anatomical lobectomy;
• Anticipated requirement for sleeve resection, pneumonectomy, or pulmonary autotransplantation to remove the affected lobe;
• Prior thoracic radiotherapy before the initiation of surgical treatment;
• History of allogeneic tissue or solid organ transplantation;
• Diagnosis of an autoimmune disease within 3 months prior to surgery, or currently receiving long-term systemic corticosteroid therapy (at a dose >10 mg/day of prednisone or equivalent) or any other form of immunosuppressive therapy;
• History of or current non-infectious interstitial lung disease requiring corticosteroid therapy;
• Presence of viral infectious diseases during the screening period:

• Seropositivity for human immunodeficiency virus (HIV);
• Active hepatitis B: positive for hepatitis B surface antigen (HBsAg) with an HBV-DNA viral load >500 IU/mL or >2000 copies/mL;
• Active hepatitis C: positive for hepatitis C virus (HCV) antibody with an HCV-RNA viral load above the upper limit of normal (ULN);
• Poorly controlled hypertension despite medical therapy, defined as systolic blood pressure >150 mmHg or diastolic blood pressure >90 mmHg (adjustment of antihypertensive medications is permitted prior to study initiation, provided that the average of the last three consecutive blood pressure readings taken prior to enrollment is ≤150/90 mmHg, with at least a 2-minute interval between each measurement);
• Active infection requiring intravenous anti-infective therapy at the time of screening;
• History of another malignancy within 3 years prior to providing informed consent, excluding cured basal cell carcinoma of the skin, carcinoma in situ of the cervix or breast, superficial bladder cancer, and localized prostate cancer. Participants with low-risk early-stage prostate cancer (T1-T2a, Gleason score ≤6, PSA <10 ng/mL) are eligible to enroll if they have received radical treatment or are under active surveillance with stable disease, regardless of prior treatment status;
• Any condition that, in the investigator's judgment, might interfere with the interpretation of study results, compromise the participant's ability to complete the study, or render study participation contrary to the participant's best interests;
• Pregnant, lactating, or planning to become pregnant; or having a positive serum pregnancy test within 7 days prior to the first study treatment;
• Poor compliance, or unwilling or unable to adhere to the protocol-specified procedures.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Guangdong Provincial People's Hospital — Guangzhou

Identifiers

NCT: NCT07617389 · KY2026-391-02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗