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Oral Paclitaxel Solution With Immunotherapy and Concurrent SBRT as Neoadjuvant Treatment for Older Adults With NSCLC
NCT07754812 · Shanghai Pulmonary Hospital, Shanghai, China
In plain English
Click the button to translate this study into plain language — what it is, who qualifies, and what participation looks like.
Official title
A Multicenter, Open-Label, Single-Arm Phase I/II Study of Oral Paclitaxel Solution Combined With an Immune Checkpoint Inhibitor and Concurrent Stereotactic Body Radiotherapy as Neoadjuvant Treatment in Older Patients With Resectable Stage IIA-IIIB Non-Small Cell Lung Cancer
About this study
Older patients with NSCLC may have reduced organ reserve, more comorbidities, and a higher risk of toxicity from standard platinum-based chemotherapy, intensive radiotherapy, or multimodality treatment. The study is designed to explore a potentially lower-intensity neoadjuvant regimen that combines oral paclitaxel solution, immune checkpoint blockade, and precision radiotherapy.
Phase I will use a conventional 3+3 dose-escalation design. Oral paclitaxel solution will be evaluated at 80, 120, and 160 mg/m² on Days 1 and 8 of each cycle, administered in divided morning and evening doses. An anti-PD-1 or anti-PD-L1 monoclonal antibody will be selected by the investigator according to standard of care and administered according to the approved prescribing information. Concurrent SBRT will be delivered at 8 Gy per fraction for 3 fractions to the primary lung tumor and selected nodal regions. The Phase I objective is to evaluate safety and identify the RP2D.
Phase II will enroll additional participants at the RP2D to evaluate antitumor activity and feasibility. Participants who remain suitable for radical lung cancer surgery are intended to undergo resection after completion of neoadjuvant treatment. The study will assess pathologic response, radiographic response, surgical feasibility, event-free survival, overall survival, and changes in immune cell subsets, circulating tumor DNA, and PD-L1 expression.
Eligibility criteria
Inclusion Criteria:
* Age 70 years or older, regardless of sex.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Histologically confirmed non-small cell lung cancer, clinical stage IIA-IIIB according to the 8th edition of the AJCC staging system.
* No evidence of distant metastasis and considered suitable for radical lung cancer surgery.
* The primary lung lesion is suitable for stereotactic body radiotherapy.
* No sensitizing driver alterations in EGFR, ALK, ROS1, or other tested actionable genes.
* Adequate major organ function, including all of the following:
* Absolute neutrophil count at least 1.5 × 10\^9/L, platelet count at least 100 × 10\^9/L, and hemoglobin at least 9 g/dL.
* Total bilirubin no more than 1.5 × the upper limit of normal; alanine aminotransferase and aspartate aminotransferase no more than 2.5 × the upper limit of normal.
* Serum creatinine no more than 1.5 × the upper limit of normal or creatinine clearance at least 60 mL/min.
* Urine protein less than 1+; if urine protein is 1+, 24-hour urine protein must be less than 500 mg.
* Blood glucose within the normal range or stable glycemic control in participants with diabetes.
* Baseline forced expiratory volume in 1 second (FEV1) at least 2 L; if FEV1 is less than 2 L, the predicted postoperative FEV1 must be greater than 800 mL as assessed by a thoracic surgeon.
* No myocardial infarction within the previous year, no unstable angina, no symptomatic severe arrhythmia, and no cardiac insufficiency.
* The participant has been fully informed and voluntarily provides written informed consent.
Exclusion Criteria:
* Prior lobectomy, thoracic radiotherapy, or systemic antitumor therapy.
* Another concurrent malignancy or a history of another malignancy cured less than 5 years before enrollment, except adequately treated cervical carcinoma in situ or basal cell or squamous cell carcinoma of the skin.
* Active autoimmune disease or a history of autoimmune disease requiring systemic immunosuppressive treatment.
* Active infection requiring systemic treatment, active tuberculosis, human immunodeficiency virus infection, active hepatitis B or hepatitis C, active syphilis, or another active transmissible infection specified by the protocol.
* Severe cardiac, hepatic, renal, or metabolic disease that precludes surgery or study treatment.
* History of interstitial lung disease or drug-induced pneumonitis, or imaging evidence of active interstitial lung disease.
* Uncontrolled large pleural effusion or pericardial effusion.
* Major surgery, severe trauma, or treatment with another investigational drug within 4 weeks before enrollment.
* Recent receipt of an anticancer vaccine or live vaccine.
* Any other condition that, in the investigator's opinion, makes the participant unsuitable for the study or may interfere with interpretation of the study results.
Study design
Enrollment target: 78 participants
Allocation: randomized
Masking: none
Age groups: older_adult
Timeline
Starts: 2026-06-25
Estimated completion: 2028-10-31
Last updated: 2026-08-10
Interventions
Drug: Oral Paclitaxel SolutionDrug: PD-1/PD-L1 inhibitorRadiation: Stereotactic Body Radiotherapy (SBRT)Procedure: Radical Lung Cancer SurgeryRadiation: Stereotactic Body Radiotherapy (SBRT)
Primary outcomes
- • Complete Response (CR) Rate in Phase 2 (2 weeks (±14 days) after surgery or radical radiotherapy)
- • Incidence of Grade 3 or Higher Treatment-Related Adverse Events (TRAE) in Phase 1 (First dose up to 1 week (±7 days) after neoadjuvant therapy)
Sponsor
Shanghai Pulmonary Hospital, Shanghai, China · other
Contacts & investigators
ContactXiaoling Xu, MD, PhD · contact · xuxl@zjcc.org.cn · +86-21-65115006
InvestigatorXiaoling Xu, MD, PhD · principal_investigator, Shanghai Pulmonary Hospital, Shanghai, China
All locations (5)
Guangdong Provincial People's HospitalNot Yet Recruiting
Guangzhou, Guangdong, China
The Affiliated Suqian Hospital of Xuzhou Medical UniversityNot Yet Recruiting
Suqian, Jiangsu, China
Shanghai Pulmonary HospitalRecruiting
Shanghai, Shanghai Municipality, China
Zhejiang Cancer HospitalNot Yet Recruiting
Hangzhou, Zhejiang, China
Lishui People's HospitalNot Yet Recruiting
Lishui, Zhejiang, China