Local Consolidative Therapy Versus Maintenance Immunotherapy After First-Line Chemoimmunotherapy in Metastatic NSCLC
A Phase II, Multicenter, Randomized, Patient-Centered Study of the Efficacy and Safety of Immediate Local Consolidative Therapy (LCT) Versus Continued Immunotherapy Maintenance or Delayed Local Therapy (Non-LCT) After First-Line Chemoimmunotherapy in Metastatic NSCLC, Assessed by MDT
This study explores the difference in progression-free survival (PFS) between local consolidative therapy (LCT arm) targeting residual lesions and continued systemic therapy (non-LCT arm) in patients with metastatic NSCLC who have achieved at least partial response (PR) following first-line chemoimmunotherapy. In this process, a multidisciplinary team (MDT) comprising surgical oncology, radiation oncology, and medical oncology will be integrated to administer local treatment modalities-including surgery, radiotherapy, and ablation-for oligometastatic lesions, aiming to address critical clinical questions regarding the optimal beneficiary population for local therapy, the best local treatment modality, and the optimal timing of local intervention.
Přehled studie
Postavení
Podmínky
Intervence / Léčba
Detailní popis
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This study incorporates both a randomized controlled trial (RCT) cohort and a real-world study (RWS) cohort.
RCT Cohort: A prospective, randomized, multicenter clinical study. The primary study population comprises patients with stage IV disease (9th edition TNM staging) who have received 4-6 cycles of first-line immunotherapy combined with platinum-based doublet chemotherapy, achieved at least partial response (PR) upon efficacy assessment, demonstrated metabolically active residual lesions on PET evaluation, and been clinically assessed by the multidisciplinary team (MDT) as amenable to individualized local therapy (e.g., ≤3 organs and ≤5 lesions, with feasibility for surgery/radiotherapy/ablation). Patients will be randomly assigned to:
Local Therapy Arm: Receiving local treatment targeting residual lesions, followed by physician-assessed continuation of maintenance systemic therapy or surveillance monitoring; optional local treatment modalities include surgery, radiotherapy, and ablation. Assessment of residual lesions will be primarily based on imaging examinations including PET-CT and brain MRI. PET evaluation of residual lesions will primarily reference the PERCIST (PET Response Criteria in Solid Tumors) criteria. Compared with baseline imaging, lesions with metabolic activity exceeding that of the mediastinal blood pool or liver on PET evaluation will be considered potentially active residual lesions. The final determination shall be made through multidisciplinary assessment jointly by a radiologist or nuclear medicine physician with more than 10 years of clinical experience, together with thoracic surgeons, pulmonologists, and radiation oncologists.
Systemic Therapy Arm: Continuation of systemic maintenance therapy until disease progression (PD) or intolerable toxicity; upon PD, patients may undergo MDT reassessment for potential local therapy opportunities.
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Primary Endpoint:
Progression-Free Survival (PFS): Time from randomization to first documented disease progression or death from any cause.
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Secondary Endpoints:
Overall Survival (OS): Time from randomization to death from any cause. Safety of local consolidative therapy. Impact of different local consolidative treatment modalities on prognosis. Time from local consolidative therapy to recurrence/progression of previously existing metastatic lesions.
Time from local consolidative therapy to development of new metastatic lesions.
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Exploratory Endpoints:
Tumor Immune Microenvironment (TiME) and prognosis. Tumor dormancy characteristics. Clinical outcomes of different treatment choices after disease progression (PD) in the control arm.
Correlation between ctDNA-based minimal residual disease (MRD) status before and after randomization and prognosis.
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RCT Cohort: The time from randomization to disease progression (PD) or death in the control arm following induction therapy was 6 months. Assuming that the experimental arm combined with local therapy could be extended to 11 months (based on clinical experience and literature inference), with a one-sided α of 0.05, power of 80%, accrual period of 12 months, and a randomization ratio of 2:1, the total required sample size was calculated to be 105 patients (with a total of 76 required events), comprising 70 patients in the experimental arm and 35 patients in the control arm. Considering an 8%-10% dropout rate, a total of 117 patients are planned for enrollment.
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RWS Cohort: This cohort does not prespecify statistical hypotheses. It is designed to observe patients who met the eligibility criteria during the RCT study period but were unable to be enrolled in the RCT for various reasons. This cohort will serve to supplement the safety and clinical benefit data of the experimental arm in the RCT cohort. Based on epidemiological projections from our center, approximately 50 patients are expected to be enrolled during this period.
Typ studie
Zápis (Odhadovaný)
Fáze
- Fáze 2
Kontakty a umístění
Studijní kontakt
- Jméno: Wen-Zhao Zhong, MD, PhD
- Telefonní číslo: +86-020-83827812
- E-mail: syzhongwenzhao@scut.edu.cn
Studijní záloha kontaktů
- Jméno: Rui Fu, MD, PhD
- Telefonní číslo: +86-020-83827812
- E-mail: ruifu66@foxmail.com
Studijní místa
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Guangzhou
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Guangzhou, Guangzhou, Čína, 510080
- Guangdong Provincial People's Hospital
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Kontakt:
- Wen-Zhao Zhong, MD,PhD
- Telefonní číslo: +86-020-83827812
- E-mail: ruifu66@foxmail.com
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
Inclusion Criteria:
- Voluntary participation in the study with signed informed consent;
- Age ≥18 years, both male and female;
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1;
- Estimated life expectancy ≥12 months;
- Histologically/cytologically confirmed non-small cell lung cancer (NSCLC) at initial diagnosis, with TNM stage IV (IASLC 9th edition);
- Absence of actionable genetic mutations related to EGFR/ALK/ROS1 and other druggable targets;
- Completion of 4-6 cycles of immunotherapy (PD-1/PD-L1 monoclonal antibody) combined with platinum-based doublet chemotherapy prior to enrollment;
- Achievement of partial response (PR) or complete response (CR) as assessed by RECIST 1.1 criteria;
- Presence of metabolically active residual lesions on PET evaluation, and clinical assessment by the multidisciplinary team (MDT)* indicating feasibility of individualized local therapy (e.g., ≤3 organs and ≤5 lesions, amenable to surgery/radiotherapy/ablation);
- Adequate organ function.
Exclusion Criteria:
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Expected to be unable to tolerate surgery, radiation therapy, or ablation;
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Unable to receive local treatment for all active residual lesions;
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Patients with a confirmed history of malignant pleural effusion or pleural dissemination;
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Pathologically diagnosed with neuroendocrine cancer at initial diagnosis (including small cell lung cancer, combined small cell lung cancer, large cell neuroendocrine carcinoma, mixed large cell neuroendocrine carcinoma, and carcinoid). Patients who do not show neuroendocrine components at initial diagnosis but develop such components in post-surgical pathology may be included;
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Previously received allogeneic tissue or solid organ transplantation;
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History of interstitial lung disease requiring steroid treatment (non-infectious) or currently suffering from interstitial lung disease requiring steroid treatment;
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Presence of viral infectious diseases during screening:
- Positive serum test for human immunodeficiency virus (HIV);
- Active hepatitis B: positive hepatitis B surface antigen (HBsAg) and HBV-DNA quantitative test >500 IU/mL or >2000 copies/mL;
- Active hepatitis C: positive hepatitis C virus (HCV) antibody and HCV-RNA quantitative test above the upper limit of normal;
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Participants with uncontrolled hypertension defined as systolic blood pressure >150 mmHg or diastolic blood pressure >90 mmHg (adjustment of antihypertensive medications is allowed prior to study initiation, but the average of the most recent three consecutive blood pressure readings before enrollment must be ≤150/90 mmHg) (each measurement separated by at least 2 minutes);
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Active infection requiring intravenous antimicrobial therapy at screening;
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Diagnosis of another malignancy within 3 years prior to signing informed consent, excluding cured cases of cutaneous basal cell carcinoma, cervical or breast in situ carcinoma, superficial bladder cancer, localized prostate cancer; participants with low-risk early-stage prostate cancer (T1-T2a stage, Gleason score ≤6, PSA <10 ng/mL) are eligible if they have undergone curative treatment or are under active surveillance with stable disease, regardless of whether they have received treatment;
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Conditions that may interfere with interpretation of study results or affect the participant's ability to complete the entire study, or where, in the investigator's judgment, participation does not serve the participant's best interest;
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Pregnant, breastfeeding, or planning pregnancy; positive pregnancy test within 7 days prior to first study treatment;
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Poor compliance, unwillingness or inability to follow the study procedures as required.
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
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Experimentální: LCT
Receiving local treatment targeting residual lesions, followed by physician-assessed continuation of maintenance systemic therapy or surveillance monitoring; optional local treatment modalities include surgery, radiotherapy, and ablation. Assessment of residual lesions will be primarily based on imaging examinations including PET-CT and brain MRI. PET evaluation of residual lesions will primarily reference the PERCIST (PET Response Criteria in Solid Tumors) criteria. Compared with baseline imaging, lesions with metabolic activity exceeding that of the mediastinal blood pool or liver on PET evaluation will be considered potentially active residual lesions. The final determination shall be made through multidisciplinary assessment jointly by a radiologist or nuclear medicine physician with more than 10 years of clinical experience, together with thoracic surgeons, pulmonologists, and radiation oncologists. |
Patients with stage IV disease (9th edition TNM staging) who have received 4-6 cycles of first-line immunotherapy combined with platinum-based doublet chemotherapy, achieved at least partial response (PR) upon efficacy assessment, demonstrated metabolically active residual lesions on PET evaluation, and been clinically assessed by the multidisciplinary team (MDT) as amenable to individualized local therapy. And then receiving local treatment targeting residual lesions, followed by physician-assessed continuation of maintenance systemic therapy or surveillance monitoring; optional local treatment modalities include surgery, radiotherapy, and ablation.
Ostatní jména:
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Žádný zásah: non-LCT
Continuation of systemic maintenance therapy until disease progression (PD) or intolerable toxicity; upon PD, patients may undergo MDT reassessment for potential local therapy opportunities. |
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Časové okno |
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Progression-Free Survival (PFS)
Časové okno: Time from randomization to the date of the first documentation of disease progression according to Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) or death from any cause, whichever is earlier, assessed up to 60 months.
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Time from randomization to the date of the first documentation of disease progression according to Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) or death from any cause, whichever is earlier, assessed up to 60 months.
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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Overall Survival (OS)
Časové okno: time from randomization to the date of death from any cause, assessed up to 60 months.
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time from randomization to the date of death from any cause, assessed up to 60 months.
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Safety of local consolidative therapy.
Časové okno: 30 days (±5 days) after local therapy or prior to the first maintenance therapy following local therapy.
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Safety follow-up will be conducted at 30 days (±5 days) after local therapy or prior to the first maintenance therapy following local therapy. Occurrence and severity of adverse events, with severity determined by NCI CTCAE v6.0 criteria. |
30 days (±5 days) after local therapy or prior to the first maintenance therapy following local therapy.
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Impact of different local consolidative treatment modalities on prognosis.
Časové okno: When a PFS or OS event occurs
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Impact of different local consolidative treatment modalities on PFS and OS. |
When a PFS or OS event occurs
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Time from local consolidative therapy to recurrence/progression of previously existing metastatic lesions.
Časové okno: From date of local consolidative therapy until the date of first documented recurrence/progression of previously existing metastatic lesions, assessed up to 60 months..
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From date of local consolidative therapy until the date of first documented recurrence/progression of previously existing metastatic lesions, assessed up to 60 months..
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Time from local consolidative therapy to development of new metastatic lesions.
Časové okno: From date of local consolidative therapy until the date of first documented new distant metastasis, assessed up to 60 months.
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From date of local consolidative therapy until the date of first documented new distant metastasis, assessed up to 60 months.
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Spolupracovníci a vyšetřovatelé
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Odhadovaný)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Další relevantní podmínky MeSH
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