A Phase II, Two Parallel Group Study of Neoadjuvant and Adjuvant Targeted Treatment in NSCLC With BRAF V600 or MET Exon 14 Mutations
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Pathological complete response (pCR) rate
研究概览
简要总结
This is a Phase II, two parallel group study assessing the efficacy and safety of neoadjuvant and adjuvant targeted therapy in patients with stage IB-IIIA NSCLC harboring BRAF V600 or MET exon14 mutations.
详细描述
This is a Phase II, two parallel group study assessing the efficacy and safety of neoadjuvant and adjuvant targeted therapy in patients with stage IB-IIIA NSCLC harboring BRAF V600 or MET exon14 mutations. Eligible patients with BRAF V600 mutations will receive dabrafenib 150mg bid plus trametinib 2mg qd for 8 weeks before a surgical resection (neoadjuvant), and followed by up to 4 cycles of adjuvant chemotherapy, if receive adjuvant chemotherapy, up to four cycles, chemo regimen according to investigators' choice, and up to 2 years of adjuvant targeted therapy with dabrafenib plus trametinib. For patients with MET exon14 mutations, they will receive capmatinib 400mg bid for 8 weeks before surgery (neoadjuvant), followed by up to 4 cycles of adjuvant chemotherapy, about adjuvant chemotherapy same as BRAF V600 group, and up to 2 years of adjuvant targeted therapy with capmatinib post-surgery. During treatment, patients will visit their physicians regularly for disease and safety assessment. After the end of treatment, survival follow-up will be conducted every 3 months for up to 3 years. Approximately 40 evaluable patients will be enrolled in the study (20 patients in each cohort).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18 years or older.
- •Histologically or cytologically diagnosed stage IB-IIIA and selected IIIB (T3N2, T4N2) NSCLC.
- •Presence of BRAF V600 mutation or METex14 skip mutation in tumor (by PCR or NGS) or blood (by NGS) (pre-treatment biopsy confirmed) in local or other Clinical Laboratory Improvement Amendments (CLIA)-certified lab.
- •Patients whose pre-surgical lesion is measurable, Eligible for surgical resection and scheduled for surgery within 2 weeks after the last does of neoadjuvant treatment.
- •ECOG performance-status score of 0 or
- •No previous anticancer therapy.
- •Patients with stage II or higher non-small-cell lung cancer (NSCLC) and those with suspected brain metastases should have brain imaging (CT or MRI) prior to enrollment to exclude brain metastasis.
- •Could provide pretreatment tumor samples available for biomarker analysis. The subject should have good compliance, who would participate in the research voluntarily, and sign the informed consent.
排除标准
- •Patients with unresectable (regardless of stage) or metastatic disease (stage IV) or brain metastases.
- •Contain neuroendocrine carcinoma tumor histology.
- •Major surgery within 4 weeks before enrollment, or who have not recovered from side effects of related procedures.
- •History of current interstitial lung disease or pneumonitis.
- •Patients with conditions requiring systemic corticosteroids (>10 mg daily prednisone or equivalent) or immunosuppressive medication within 14 days of the first dose of study drug (Inhaled or topical steroids and adrenal-replacement steroids are allowed).
- •History of other malignancies within 5 years (excluding basal cell carcinoma of the skin or other carcinoma in situ that has been resected).
- •Pregnant or lactating women.
- •Those who are allergic to the research drug or its components.
- •Subjects who are deemed unable to comply with the study requirements or complete the study.
- •Those with acquired immunodeficiency syndrome, or any uncontrolled medical disorder, or insufficient function of bone marrow or other important organs.
研究组 & 干预措施
Cohort 1: BRAF V600 mutation
Dabrafenib + Trametinib
干预措施: Dabrafenib + Trametinib (Drug)
Cohort 2: MET ex14 skip mutation
Capmatinib
干预措施: Capmatinib (Drug)
结局指标
主要结局
Pathological complete response (pCR) rate
时间窗: up to 2 years
pCR rate is defined as the percentage of participants with no residual viable tumor cells.
次要结局
- Event-free survival (EFS)(up to 3 years)
- Disease-free survival (DFS)(up to 3 years)
- Overall survival (OS)(up to 3 years)
- Major pathological response (MPR) rate(up to 2 years)
研究者
Li Zhang, MD
Director
Sun Yat-sen University