This umbrella trial directed by next generation sequencing (NGS) includes patients with treatment-naive unresectable stage III non-small-cell lung cancer (NSCLC). The aim of the umbrella study is to evaluate the efficacy of induction NGS-directed targeted therapies followed by surgery for stage III NSCLC patients whose tumor harbors a rare mutation.
Stage III non-small-cell lung cancer (NSCLC) patients account for about one-third of newly diagnosed NSCLC, with a large population and strong heterogeneity, posing significant challenges for clinical treatment. Concurrent chemoradiotherapy plus immune checkpoint inhibitors is the recommended therapeutic approach for patients with unresectable stage III non-small cell lung cancer (NSCLC), although surgery offers the chance of cure. However, existing evidence suggests that patients with driver mutation positive NSCLC have limited benefits from immunotherapy. There is still controversy over the definition of 'unresectable', and some stage IIIA and specific stage IIIB-N2 patients may also benefit from comprehensive surgical treatment. Emerging data supports the use of targeted therapies in NSCLC patients with a rare mutation. The aim of this umbrella study is to explore the efficacy of induction next generation sequencing (NGS)-directed targeted therapies followed by surgery for unresectable stage III NSCLC patients whose tumor harbors a rare mutation (Without EGFR Sensitizing Mutations).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
120
300 mg orally once a day, 28 days as one cycle.
300 mg orally once a day, 28 days as one cycle.
400 mg orally once a day, 28 days as one cycle.
Sun Yat-sen University Cancer Center
Guangzhou, Guangdong, China
RECRUITINGResectability rate
Time frame: Baseline to 6 months
Adverse Events
Adverse Events were monitored according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.
Time frame: Baseline to 24 months
Two-year disease-free survival
Disease-free survival was assessed from randomization to disease recurrence or death as a result of any cause.
Time frame: 2 years after the last patient is randomized
Two-year overall survival
Overall survival was assessed from randomization to death as a result of any cause.
Time frame: 2 years after the last patient is randomized
Number of participants with perioperative complications
Time frame: Baseline to 12 months
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100 mg orally twice daily, 28 days as one cycle.
600 mg or 400 mg (weight \<50 kg) orally once a day, 28 days as one cycle.
400 mg orally once a day, 28 days as one cycle.
Dabrafenib 150 mg orally twice daily, 28 days as one cycle. Trametinib 150 mg orally twice daily, 28 days as one cycle.
800 mg daily orally, 28 days as one cycle.
225 mg daily orally, 28 days as one cycle.