Combining Furmonertinib With Local Therapy for Inoperable Early-stage Lung Cancer: A Phase II Trial

Phase 2Not Yet RecruitingNCT07517640

Shanghai Pulmonary Hospital, Shanghai, China45 enrolled

Overview

The goal of this Single-arm, Phase II clinical trial is to learn whether ablation or stereotactic radiotherapy combined with furmonertinib can treat early-stage non-small cell lung cancer in patients who are inoperable or refuse surgery. The main purposes of this study is to answer: Can ablation or stereotactic radiotherapy combined with furmonertinib improve survival in patients with early-stage NSCLC who are inoperable or refuse surgery? Can ablation or stereotactic radiotherapy combined with furmonertinib reduce recurrence in patients with early-stage NSCLC who are inoperable or refuse surgery?

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Non-small Cell Lung Cancer

Interventions

ablationPROCEDURE

1. Immobilization and image guidance: Supine or prone position; vacuum cushion or mask to limit motion. CT guidance for entry point, angle, and depth; ultrasound for selected peripheral lesions. 2. Ablation target planning: Ablation zone should cover GTV with ≥5-10 mm margin. For tumors near critical structures, pursue adequate margin when safe; consider heat sink or thermal isolation. 3. Ablation procedure: Choose MWA, RFA, or cryoablation based on tumor size, location, anatomy, and resources. 4. Intraprocedural monitoring and endpoint assessment: CT during/after ablation to confirm ground-glass opacity covers tumor with planned margin. Ablation zone ≥5 mm beyond tumor = technical success. If inadequate, reposition and supplement. 5. Post-procedure management and follow-up: Monitor vital signs; manage complications as needed.

stereotactic body radiotherapyRADIATION

1. Immobilization: Use a thermoplastic mask or vacuum cushion for immobilization based on the treatment site. 2. CT simulation: After immobilization and stabilization of breathing, laser alignment is performed, followed by 4D-CT simulation (preferred) or conventional CT simulation. 3. Radiotherapy target delineation and dose: GTV includes the primary lung tumor and metastatic lymph nodes after chemotherapy. A 5-mm margin is added to form the PTV. 4. Radiotherapy plan: For peripheral lesions: 48 Gy in 4 fractions or 50 Gy in 5 fractions; for central lesions: 60 Gy in 8 fractions or 60 Gy in 10 fractions.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Voluntarily participate in the clinical study * Aged ≥ 18 years at the time of signing the informed consent form * Histologically or cytologically confirmed early-stage T1-3 N0 NSCLC, or patients with multiple primary lesions or solitary pulmonary parenchymal recurrence * Confirmed presence of EGFR-sensitive mutations by genetic testing, including but not limited to Exon 19 deletion, L858R, G719X, L861Q, S768I, and their compound mutations * ECOG performance status score of 0-2 * Deemed medically inoperable or refuse surgery after multidisciplinary evaluation * Pulmonary lesions suitable for ablation or radiotherapy (either modality) * Adequate major organ function Exclusion Criteria: * Known severe allergic reaction (NCI-CTCAE v5.0 grade ≥ 3) to any monoclonal antibody or any excipient of the study drug * Known contraindications to ablation or radiotherapy * Failure to meet the minimum requirements for target coverage and dose constraints to organs at risk in the SABR treatment plan * Active infection requiring systemic anti-infective therapy within 14 days prior to the first dose * Patients with hepatitis B (hepatitis B surface antigen \[HBsAg\] positive and detectable HBV-DNA indicating viral replication); hepatitis C (hepatitis C virus \[HCV\] antibody positive and detectable HCV-RNA indicating viral replication) * Receipt of curative-intent radiotherapy within 3 months prior to the first dose * Major surgery within 28 days prior to the first dose (major surgery in this study is defined as any procedure requiring at least 3 weeks of recovery before the study treatment can be administered) * Concurrent participation in another clinical study, or receipt of intervention in any other clinical trial (including drugs and devices) within 3 months or 5 half-lives prior to screening, whichever is longer * Any other condition that, in the investigator's judgment, makes the patient unsuitable for participation in this study

Outcomes

Primary Outcomes

2-year EFS rate

defined as the proportion of patients who experience no event (including disease progression, recurrence, distant metastasis, discontinuation of treatment for any reason, or death) within 24 months from the start of treatment, relative to the total enrolled population.

Time frame: Within two years after the treatment

Secondary Outcomes

3-year EFS rate

defined as the proportion of patients who experience no event (including disease progression, recurrence, distant metastasis, or death) within 36 months from the start of treatment, relative to the total enrolled population.

Time frame: Within three years after the treatment

overall survival

defined as the time from the start of treatment to death from any cause

Time frame: through study completion, an average of 5 year

Local control rate (LCR)

defined as the proportion of patients who show no radiographic enlargement or recurrence of the primary tumor during follow-up

Time frame: through study completion, an average of 1 year

Time to distant metastasis

defined as the time from the start of treatment to the first occurrence of distant metastasis (e.g., to bone, brain, liver, or distant lymph nodes)