Surgery After Verifying Existing Disease in Locally Advanced Operable Lung Cancer (SAVED LUNG Study): A Pilot Study
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 14
- 试验地点
- 2
- 主要终点
- Safety
研究概览
简要总结
The SAVED LUNG study is a pilot Phase I trial evaluating safety and feasibility of observation versus standard-of-care surgery in operable Stage II-III (excluding N3) NSCLC patients (PD-L1 ≥50%) who achieve complete clinical response following neoadjuvant platinum-doublet chemotherapy and immunotherapy. Participants are randomized to observation or surgery after rigorous restaging, with primary endpoints focusing on safety and feasibility. Secondary objectives include rates of cross-over to surgery, event-free survival, and overall survival, while exploratory endpoints examine ctDNA clearance and its association with clinical response.
详细描述
After neoadjuvant therapy, all participants undergo intensified re-staging invasive and non-invasive modalities to assess for complete clinical response:
- Chest CT;
- PET/CT scan;
- Bronchoscopy;
- EBUS;
- EUS;
- Re-biopsy of lesions that were deemed to be positive for cancer; this includes re-biopsies of all positive lymph nodes and transthoracic needle aspiration of tumors.
Participants with complete clinical response defined by absence of disease as measured by all the above modalities will be randomized 1:1 to either observation or surgery.
Only patients with complete clinical response will proceed to the randomization stage of the trial. Block randomization will occur 1:1 with two participants per block. All other patients will remain on study and undergo therapy as per standard-of-care and will have follow-up on study. Both groups will have blood collected for ctDNA at this stage. For participants in the surgery arm, the blood sample will be 3 weeks after surgery, while participants in surveillance only arm will have the blood sample 3 weeks after randomization.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •> 18 years of age
- •The participant has provided documented informed consent for the trial.
- •Histologically confirmed (by core biopsy) NSCLC and confirmed clinical stages II-III (excluding N2) NSCLC (AJCC 8th edition) amenable to receive neoadjuvant chemo-immunotherapy defined by: nivolumab 3mg/kg Q3W in combination with platinum doublet chemotherapy (cisplatin or carboplatin with paclitaxel or pemetrexed Q3W) for 3 cycles.
- •PD-L1 tumor proportion score >50%
- •Has no history of immunodeficiency, HBV, HCV, HIV.
- •For female participants:
- •Has no active pregnancy (Refer to "Female participants").
- •For a woman of child-bearing potential (WOCBP), use of a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) during the intervention period and for at least 180 days after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period.
- •A WOCBP must have a negative highly sensitive pregnancy test ([urine or serum] as required by local regulations) within either 24 hours (urine) or 72 hours (serum) before the first dose of study intervention.
- •If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
- •Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
- •Has adequate hematological, renal and hepatic function per Investigator discretion required for platinum-doublet chemotherapy plus immunotherapy.
- •Has signed the written consent.
排除标准
- •Has one of the following tumor locations/types:
- •NSCLC involving the superior sulcus
- •Large cell neuro-endocrine cancer (LCNEC)
- •Sarcomatoid tumor
- •Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
- •Has an active infection requiring systemic therapy.
- •Has had an allogenic tissue/solid organ transplant.
- •Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
- •Has known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the trial.
- •Has a known additional malignancy that is progressing or requires active treatment within the past (5 years). Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, bladder carcinoma, or carcinoma in situ (eg, in situ cervical cancer or breast carcinoma) that have undergone potentially curative therapy are not excluded.
研究组 & 干预措施
Observation without surgery
Participants undergo surveillance without surgery, including a low-dose CT scan of the thorax and upper abdomen, ECOG assessment, and physical examination every 3 months for the first 12 months. Additional ctDNA testing is performed 3 weeks post-randomization and at 6 months. Long-term follow-up includes similar assessments every 6-12 months up to 5 years.
干预措施: Observation without surgery (Other)
Standard-of-care surgery
Participants undergo surgery followed by the same surveillance schedule as Arm A. ctDNA testing is conducted 3 weeks post-surgery and again at 6 months. Surveillance includes low-dose CT scans, physical examinations, and ECOG assessments every 3 months for 12 months, with long-term monitoring at regular intervals up to 5 years.
干预措施: Standard-of-care surgery (Procedure)
结局指标
主要结局
Safety
时间窗: From randomization through 5 years of follow-up
Adverse events will be determined as type and grade using the CTCAE v5.0.
Feasibility
时间窗: First two years of the study
Recruitment rate will be defined as the total number of patients recruited (consented) out of the total number of patients approached.
次要结局
- Complete clinical response(Restaging 3 weeks after completion of neoadjuvant therapy (3 cycles of nivolumab and platinum-doublet chemotherapy))
- Cross-over to surgery(From randomization through 5 years of follow-up)
- Event-free survival (EFS) at 12 months(12 months following randomization)
- Overall survival (OS) at 12 months(12 months following randomization)
- Circulation tumor DNA (ctDNA) clearance(3 weeks post-randomization (surveillance arm) or 3 weeks post-surgery (standard-of-care surgery arm))