A Prospective, Multicenter Study on the Safety and Efficacy of Furmonertinib Combined With Local Chest Radiotherapy in EGFR+ Non-small Cell Lung Adenocarcinoma Patients With Malignant Pleural Effusion
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 63
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
This study is designed as a prospective, multi-center investigation to explore the efficacy and safety of furmonertinib combined with upfront thoracic radiotherapy with or without metastatic lesion radiotherapy in subjects with EGFR-mutant NSCLC and malignant pleural effusion (MPE), aiming to provide additional evidence-based medical support for optimizing the management of NSCLC-MPE subjects. In addition, peripheral blood ctDNA next-generation sequencing (NGS) will be performed at two time points-before the first furmonertinib treatment and one month after the completion of thoracic radiotherapy-to identify subpopulations most likely to benefit from this therapeutic approach and to elucidate resistance mechanisms specific to the radiotherapy-plus-furmonertinib combination, ultimately facilitating more personalized care for these subjects.
详细描述
This study is designed as a prospective, multi-center investigation that plans to enroll 63 subjects with stage IV non-small cell lung adenocarcinoma harboring EGFR-sensitive mutations (exon 19 deletion or exon 21 L858R mutation) complicated by malignant pleural effusions (MPE). Subjects will receive an initial 10-12 weeks of furmonertinib therapy with or without therapeutic thoracentesis to achieve adequate control of MPE, followed by thoracic radiotherapy targeting residual primary pulmonary lesions, regional lymph node metastases, and pleural metastatic lesions, with or without radiotherapy to osseous, adrenal, hepatic, or brain metastases (total irradiated sites ≤6, involved organs ≤3). For brain metastases, consolidative radiotherapy will be withheld if residual tumor diameter is <1 cm after furmonertinib treatment and no significant neurological symptoms are present.
- Radiotherapy techniques: Depending on the availability at each participating center, subjects may receive one of the following modalities:
- Intensity-modulated radiation therapy (IMRT),
- Volumetric-modulated arc therapy (VMAT),
- Stereotactic body radiation therapy (SBRT),
- Stereotactic radiosurgery (SRS), or
- Fractionated stereotactic radiosurgery (fSRS).
- Prescription doses for primary and metastatic lesions: Based on institutional technical capabilities and the dose constraints of organs at risk in the radiotherapy plan, the following stereotactic or hypofractionated regimens are permissible:
- Hypofractionated radiotherapy: DT 3000-4000 cGy/10 fractions, 3-4 Gy/fraction, once daily, 5 days/week;
- SBRT: 27-50 Gy/3-5 fractions, 8-10 Gy/fraction, once daily, every other day;
- SRS (for brain metastases): 20-24 Gy/fraction;
- fSRS (for brain metastases): 27 Gy/3 fractions or 30 Gy/5 fractions.
Oral furmonertinib will be withheld before, during, and for 3 days after the completion of radiotherapy. Furmonertinib maintenance will be resumed 3 days after radiotherapy completion and continued until disease progression or unacceptable toxicity. We hypothesize that this treatment paradigm will effectively control MPE, significantly improve progression-free survival (and potentially overall survival), with manageable treatment-related toxicity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Masking Description
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years.
- •Histologically or cytologically confirmed advanced lung adenocarcinoma.
- •Unlimited number of metastatic lesions, but with involvement of no more than 3 organs.
- •Previously untreated, clinical stage IV disease per AJCC/UICC 9th edition.
- •Presence of pleural effusion as indicated by chest CT or ultrasound; cytological confirmation of malignant cells in the pleural effusion is preferred. If malignant cells are not detected in the pleural effusion, chest CT with contrast or whole-body PET/CT must demonstrate unequivocal pleural nodular metastases.
- •After 8-10 weeks of furmonertinib therapy with or without therapeutic thoracentesis, the overall radiographic response is assessed as effective (CR + PR + SD), and malignant pleural effusion is adequately controlled (defined as no pleural effusion or only minimal pleural effusion on ultrasound or chest CT: maximum depth < 3 cm, estimated volume < 500 mL). Concurrent minimal pericardial effusion is permissible (defined as maximum diastolic width < 1 cm on echocardiography, estimated volume < 100 mL).
- •No prior thoracic radiotherapy.
- •Positive for EGFR-sensitive mutations (exon 19 deletion or exon 21 L858R).
- •No prior systemic anticancer therapy.
- •ECOG performance status 0-2, with a life expectancy of ≥ 12 weeks.
- •At least one measurable lesion per RECIST 1.
- •Adequate bone marrow function to tolerate anticancer treatment: WBC ≥ 3 × 10⁹/L, Hb ≥ 80 g/L, PLT ≥ 75 × 10⁹/L, and absolute neutrophil count (NEUT) ≥ 1.5 × 10⁹/L.
- •Essentially normal hepatic and renal function:
- •Serum creatinine ≤ 1.5 × upper limit of normal (ULN) or creatinine clearance (CrCl) ≥ 50 mL/min;
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN (≤ 5 × ULN is acceptable in patients with liver metastases);
- •Total bilirubin (TBIL) ≤ 1.5 × ULN;
- •Albumin ≥ 30 g/L and prealbumin ≥ 150 g/L.
- •Asymptomatic brain metastases.
- •Written informed consent obtained from all subjects.
排除标准
- •Pre-existing interstitial lung disease (ILD) or infectious fever prior to treatment.
- •Radiographic progression (PD) after 8-10 weeks of TKI therapy, or development of grade ≥ 2 ILD.
- •Concurrent autoimmune disease requiring long-term oral corticosteroid therapy.
- •Severe anemia.
- •Known hypersensitivity to furmonertinib.
- •Significant respiratory symptoms (e.g., chest tightness, cough) that preclude tolerance to radiotherapy.
- •Active hepatitis B or C virus infection with concomitant grade > 2 hepatic impairment. Patients may be considered eligible if liver function recovers to grade 1 after active hepatoprotective therapy and antiviral treatment.
- •Poorly controlled or continuously progressive pleural effusion after 8-10 weeks of furmonertinib therapy.
- •Symptomatic brain metastases.
研究组 & 干预措施
experimental
Subjects will receive an initial 10-12 weeks of furmonertinib therapy with or without therapeutic thoracentesis to achieve adequate control of malignant pleural effusion, followed by thoracic radiotherapy targeting residual primary pulmonary lesions, regional lymph node metastases, and pleural metastatic lesions, with or without radiotherapy to osseous, adrenal, hepatic, or brain metastases. Oral furmonertinib will be withheld before, during, and for 3 days after radiotherapy. Resumption of furmonertinib maintenance will occur 3 days after radiotherapy completion and continue until disease progression or unacceptable toxicity.
干预措施: Thoracic Radiotherapy (TRT) (Radiation)
experimental
Subjects will receive an initial 10-12 weeks of furmonertinib therapy with or without therapeutic thoracentesis to achieve adequate control of malignant pleural effusion, followed by thoracic radiotherapy targeting residual primary pulmonary lesions, regional lymph node metastases, and pleural metastatic lesions, with or without radiotherapy to osseous, adrenal, hepatic, or brain metastases. Oral furmonertinib will be withheld before, during, and for 3 days after radiotherapy. Resumption of furmonertinib maintenance will occur 3 days after radiotherapy completion and continue until disease progression or unacceptable toxicity.
干预措施: Furmonertinib (Drug)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: From date of first dose to date of first documented disease progression or death from any cause, assessed up to 24 months.
PFS defined as time from first dose of furmonertinib to disease progression per RECIST v1.1 or death from any cause, whichever occurs first.
次要结局
- Overall Response Rate (ORR)(Evaluations are performed at 1 month post-radiotherapy, and subsequently every 3 months, with a total follow-up period of 18 months.)
- Malignant pleural effusion recurrence rate(Evaluations are performed at 1 month post-radiotherapy, and subsequently every 3 months, with a total follow-up period of 18 months.)
- Disease Control Rate (DCR)(Evaluations are performed at 1 month post-radiotherapy, and subsequently every 3 months, with a total follow-up period of 18 months.)
- Adverse event(From date of first dose to 30 days after last dose .)
- Peripheral Blood ctDNA Level(Next-generation sequencing (NGS) was used to detect circulating tumor DNA (ctDNA) in peripheral blood samples collected before the first furmonertinib treatment and 1 month after the completion of thoracic radiotherapy (2 time points in total).)
- Overall Survival (OS)(From date of first dose to date of death from any cause, assessed up to 36 months .)
- Overall Response Rate (ORR)(At 3 months after completion of radiotherapy .)
- Malignant Pleural Effusion Control Rate .(At 1, 3, and 6 months after completion of radiotherapy .)
- Disease Control Rate (DCR)(At 3 and 6 months after completion of radiotherapy)
- Incidence of Treatment-Emergent Adverse Events(From date of first dose to 30 days after last dose .)
- Peripheral Blood ctDNA Level(48 hours prior to the first furmonertinib treatment, 48 hours prior to the first thoracic radiotherapy, 48 hours after the completion of the last thoracic radiotherapy, and 48 hours after CT indicates disease progression.)
研究者
Lin Xiao
Deputy Director of the Oncology Department
Jiangmen Central Hospital