Consolidation Radiotherapy vs. Observation in Oligoresidual Advanced Non-Small Cell Lung Cancer After Chemo-Immunotherapy
NCT ID: NCT07014202
Last Updated: 2025-07-30
Study Results
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Basic Information
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RECRUITING
PHASE2
224 participants
INTERVENTIONAL
2025-06-11
2027-09-01
Brief Summary
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The primary objective is to determine if adding targeted radiation therapy to residual lesions prolongs progression-free survival in NSCLC patients with "oligo-residual lesions" (5 or fewer tumors in no more than 3 organs) following first-line chemoimmunotherapy. Researchers hypothesize that combination therapy will slow cancer progression more effectively than maintenance therapy alone.
Eligible participants include adults (18+) with advanced NSCLC who have completed 4-6 cycles of first-line chemoimmunotherapy, show limited residual disease on Positron Emission Tomography-Computed Tomography (PET-CT), and lack specific genetic mutations (Epidermal Growth Factor Receptor \[EGFR\], Anaplastic Lymphoma Kinase \[ALK\], etc.).
Patients will be randomized into two groups:
Experimental: Continuation of maintenance therapy (immunotherapy alone or with chemotherapy) plus local radiotherapy to all residual tumors Control: Continuation of maintenance therapy only
The study aims to answer:
Primary: Does adding radiotherapy slow cancer progression more effectively? Secondary: Does it improve overall survival, control residual disease, and what are its effects on safety and quality of life?
Participants will:
Be randomly assigned to a treatment group Receive their designated treatment Undergo regular check-ups and imaging scans Complete quality of life questionnaires Potentially provide blood samples for research This research will help determine optimal treatment approaches for this specific patient population to improve outcomes and quality of life.
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Detailed Description
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Study Objectives and Hypotheses:
The primary objective is to see if the addition of radiation therapy to target residual lesions will prolong the time that a patient's cancer does not get worse (progression-free survival) in patients with advanced non-small cell lung cancer (NSCLC) who have a limited number of tumors (known as "oligo-residual lesions") after receiving first-line chemotherapy in combination with immunotherapy . The researchers hypothesized that patients who receive maintenance therapy plus radiation therapy will have their cancer progress more slowly than patients who receive only maintenance therapy .
Study Population:
This study is for adult patients 18 years of age and older who have been diagnosed with advanced non-small cell lung cancer . These patients have received 4 to 6 cycles of first-line chemotherapy in combination with immunotherapy and have a limited number of tumor lesions on post-treatment imaging (PET-CT) (no more than 5 residual lesions involving no more than 3 organs) and no specific genetic mutations (e.g., Epidermal Growth Factor Receptor \[EGFR\], Anaplastic Lymphoma Kinase \[ALK\], etc.).
Study Methods:
Eligible patients will be randomly assigned to one of two groups :
Experimental group: continuation of maintenance therapy (either immunotherapy or chemotherapy combined with immunotherapy, depending on the previous regimen) and local radiotherapy to all residual tumor lesions.
Control group: Continuation of maintenance therapy only.
Key questions to be answered by the study:
Primary question: is the addition of local radiotherapy more effective in slowing cancer progression than maintenance therapy alone in this group of lung cancer patients? Secondary questions include: Does the addition of radiotherapy prolong overall survival? How effective is it in controlling residual disease? What is the safety (side effects) of the treatment and how does it affect the patient's quality of life?
What participants need to do:
Be randomized to one of the treatment groups . Receive the appropriate treatment (maintenance therapy, or maintenance therapy plus radiotherapy) according to their group.
Have regular check-ups and imaging scans to assess the status of the tumor. Complete questionnaires about quality of life. May be asked to provide a blood sample for research . This study will help doctors to better understand how to treat this special group of patients with advanced lung cancer, with a view to improving their outcome and quality of life.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Maintenance therapy combined with radiotherapy group
Radiotherapy Protocol:
Target all residual primary lesions and all metastatic sites (pulmonary, hepatic, osseous, lymphadenopathy). Fractionation determined by treating physician after multidisciplinary consultation. For lesions near critical organs, appropriate fractionation/total doses selected per clinical situation.
Maintenance Therapy Protocol:
Based on latest National Comprehensive Cancer Network (NCCN)/Chinese Society of Clinical Oncology(CSCO) guidelines for stage IV non-small cell lung cancer (NSCLC). For lung adenocarcinoma: Following 4-6 cycles of first-line therapy (pemetrexed+platinum+immunotherapy) Maintenance: Pemetrexed (500mg/m²) + pembrolizumab 200mg IV q3w. Duration: Maximum 24 months (until week 96, disease progression, unacceptable toxicity, consent withdrawal, or other termination criteria). All trial patients receive immunotherapy maintenance
Immunotherapy (with or without chemotherapy) maintenance therapy combined with radiotherapy
Immunotherapy (with or without chemotherapy) maintenance therapy combined with radiotherapy in patients with advanced NSCLC who have not progressed after 4-6 cycles of first-line platinum-containing chemotherapy combined with immunotherapy and who have an oligo-residual status confirmed by PETCT.
Maintenance therapy
Based on latest NCCN/CSCO guidelines for stage IV NSCLC. For lung adenocarcinoma: Following 4-6 cycles of first-line therapy (pemetrexed+platinum+immunotherapy) Maintenance: Pemetrexed (500mg/m²) + pembrolizumab 200mg IV q3w. Duration: Maximum 24 months (until week 96, disease progression, unacceptable toxicity, consent withdrawal, or other termination criteria). All trial patients receive immunotherapy maintenance
Immunotherapy (with or without chemotherapy) maintenance therapy
Immunotherapy (with or without chemotherapy) maintenance therapy in patients with advanced NSCLC who have not progressed after 4-6 cycles of first-line platinum-containing chemotherapy combined with immunotherapy and who have an oligo-residual status confirmed by PETCT.
Interventions
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Immunotherapy (with or without chemotherapy) maintenance therapy combined with radiotherapy
Immunotherapy (with or without chemotherapy) maintenance therapy combined with radiotherapy in patients with advanced NSCLC who have not progressed after 4-6 cycles of first-line platinum-containing chemotherapy combined with immunotherapy and who have an oligo-residual status confirmed by PETCT.
Immunotherapy (with or without chemotherapy) maintenance therapy
Immunotherapy (with or without chemotherapy) maintenance therapy in patients with advanced NSCLC who have not progressed after 4-6 cycles of first-line platinum-containing chemotherapy combined with immunotherapy and who have an oligo-residual status confirmed by PETCT.
Eligibility Criteria
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Inclusion Criteria
2. Age ≥ 18 years;
3. Expected survival time ≥ 3 months;
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
5. Histologically or cytologically confirmed advanced non-small cell lung cancer;
6. After receiving 4-6 cycles of first-line platinum-based chemotherapy combined with immunotherapy, PET-CT evaluation shows no disease progression, with no more than 5 lesions not meeting criteria for complete metabolic response, involving no more than 3 organs;
7. All residual lesions can safely receive radiation therapy as assessed by radiation oncologists;
8. Patient can tolerate the radiotherapy process, such as maintaining fixed position;
9. At least one measurable lesion among the oligoresidual lesions according to RECIST v1.1;
12. Laboratory values at screening must meet the following criteria: a) Neutrophils ≥ 1.5×10\^9/L b) Platelets ≥ 100×10\^9/L c) Hemoglobin ≥ 90g/L (no blood transfusion within 14 days) d) Serum Cr ≤ 1×ULN, endogenous creatinine clearance \> 50ml/min (Cockcroft-Gault formula) e) AST ≤ 2.5×ULN; ALT ≤ 2.5×ULN; if liver metastases present, ALT and AST ≤ 5×ULN f) Total bilirubin ≤ 1.5×ULN (except for Gilbert's syndrome subjects, where total bilirubin must be \< 51.3μmol/L) g) Thyroid Stimulating Hormone (TSH), Free Triiodothyronine (FT3), Free Thyroxine (FT4) all within ±10% of normal range.
Exclusion Criteria
2. Previous tissue samples or peripheral blood genetic sequencing reports indicating EGFR sensitizing mutations, ALK fusion, or other gene variations that should receive standard first-line targeted therapy; squamous cell carcinoma without genetic testing is presumed negative;
3. Symptomatic brain metastases;
4. Leptomeningeal metastases;
5. Active, known, or suspected autoimmune disease (excluding vitiligo, type I diabetes, residual hypothyroidism due to autoimmune thyroiditis requiring only hormone replacement therapy, or conditions not expected to recur in the absence of external triggers);
6. Active tuberculosis (TB) infection as determined by chest X-ray, sputum examination, and clinical examination. Patients with a history of active pulmonary TB infection within the previous year, even if treated, will be excluded. Patients with a history of active pulmonary TB infection more than 1 year ago will also be excluded unless effective previous anti-TB treatment can be documented;
7. Comorbidities requiring immunosuppressive medication, or requiring systemic or local use of corticosteroids at immunosuppressive doses;
8. Pregnancy or breastfeeding;
9. Interstitial lung disease with symptomatic manifestations, or that may interfere with the detection or management of suspected drug-related pulmonary toxicity;
10. Positive for human immunodeficiency virus antibody (HIVAb), active hepatitis B virus infection (HBsAg positive and HBV-DNA \> 10\^3 copies/ml), or hepatitis C virus infection (HCV antibody positive and HCV-RNA \> lower limit of detection at the research center);
11. History of severe neurological or psychiatric disorders, including but not limited to: dementia, depression, seizures, bipolar disorder, etc.;
12. Receipt of other investigational drugs or treatments within 4 weeks prior to study randomization;
13. Use of any Chinese herbal medicines with anti-tumor activity within 2 weeks prior to study drug administration;
14. History of other malignancies (excluding non-melanoma skin cancer and the following in situ cancers: bladder, gastric, colon, endometrial, cervical/dysplasia, melanoma, or breast), unless complete remission was achieved at least 2 years prior to study enrollment and no additional therapy is required or anticipated during the study period;
15. History of severe cardiac or cerebrovascular disease, e.g., New York Heart Association (NYHA) ≥ class 2 heart failure, acute coronary syndrome (such as myocardial infarction, unstable angina, etc.) within 6 months of screening, acute cerebrovascular disease (such as transient ischemic attack, cerebral infarction, cerebral hemorrhage, etc.) within 6 months of screening;
16. Thromboembolic events requiring therapeutic intervention within 6 months prior to screening, such as unstable deep vein thrombosis, arterial thrombosis, and pulmonary embolism; excluding infusion-related thrombosis;
17. Planned vaccination or vaccination with live vaccines within 28 days prior to study randomization;
18. Other conditions deemed unsuitable for participation in this clinical trial by the investigator due to comorbidities or other circumstances.
18 Years
ALL
No
Sponsors
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Cancer Institute and Hospital, Chinese Academy of Medical Sciences
OTHER
Responsible Party
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Zhijie Wang
Professor
Principal Investigators
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Zhijie Wang
Role: STUDY_DIRECTOR
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Locations
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National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Beijing, Beijing Municipality, China
Countries
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Central Contacts
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Facility Contacts
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References
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Gao S, Li N, Wang S, Zhang F, Wei W, Li N, Bi N, Wang Z, He J. Lung Cancer in People's Republic of China. J Thorac Oncol. 2020 Oct;15(10):1567-1576. doi: 10.1016/j.jtho.2020.04.028. No abstract available.
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Pawlik TM, Scoggins CR, Zorzi D, Abdalla EK, Andres A, Eng C, Curley SA, Loyer EM, Muratore A, Mentha G, Capussotti L, Vauthey JN. Effect of surgical margin status on survival and site of recurrence after hepatic resection for colorectal metastases. Ann Surg. 2005 May;241(5):715-22, discussion 722-4. doi: 10.1097/01.sla.0000160703.75808.7d.
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Other Identifiers
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NCC4839
Identifier Type: -
Identifier Source: org_study_id
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