An Open Explorative Phase II, Open Label Study of Afatinib in the Treatment of Advanced Cancer Carrying an EGFR, a HER2 or a HER3 Mutation
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 87
- 试验地点
- 5
- 主要终点
- Response rate
研究概览
简要总结
Objective(s):To investigate the efficacy and safety of afatinib in EGFR, HER 2 and HER3 mutated cancers, regardless of cancer type, excluding EGFR mutated non-small cell lung cancer.
Methodology:Open label, genomic driven trial (basket trial)
No. of patients total entered:Optimal Simon two stage design for the three genetic driven cohorts: 10 patients will be enrolled per cancer type in the first stage and an additional 19 in the second stage (maximum total 87 patients)
Indication : cancers harbouring an EGFR mutation(excluding non-squamous non- small cell lung cancer, a registered indication), a HER2 mutation or a HER3 mutation
Test product(s) : Afatinib At progression paclitaxel will be added for those patients that have no contra-indications
dose: Starting dose of afatinib at 40 mg/day. Dose increase to 50 mg in the absence of adverse events. Stepwise dose reduction to 30,20, 10 mg/day according to drug-related adverse events.
At progression, addition of paclitaxel 80 mg/m2 weekly 3w/4 to afatinib 40 mg/day .
mode of admin. : Oral for afatinib Intravenous for paclitaxel
Duration of treatment: Continuous treatment until progression or unacceptable adverse events or withdrawal of consent.
At disease progression, add paclitaxel until progression or unacceptable adverse event or withdrawal of consent if no contra-indications.
Criteria for efficacy: Primary Endpoint:
• Response rate (CR+ PR) via RECIST v1.1
Secondary Endpoints:
- Disease control rate (CR+PR+SD)
- Progression free survival
- Overall survival
- To correlate tumor response with findings on tumor biopsies
- To investigate resistance mechanisms
- response rate (CR+ PR) determined by RECIST and progression free survival on the combination therapy of afatinib and paclitaxel
Criteria for safety: Incidence and intensity of adverse events according CTCAE v4.0
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
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
- •Women and men with locally advanced or metastatic cancers harboring either an activating EGFR mutation or a HER2 mutation or a HER3 mutation
- •Failure of at least one line of standard systemic therapy
- •No eligibility for other open genomic driven phase I, II or III trial available for these tumor genotypes
- •ECOG performance status ≤2
- •Patient with a life expectancy >3 months
- •Patients able to provide written informed consent prior to enrollment into the clinical trial.
- •Adequate organ function
排除标准
- •Non squamous non-small cell lung cancer harbouring an EGFR mutation (registered indication)
- •Chemotherapy, biological therapy or investigational agents within four weeks prior to the start of study treatment
- •Known hypersensitivity to afatinib or the excipients of any of the trial drugs
- •Prior treatment with afatinib
研究组 & 干预措施
Open label
Afatinib 40 mg/day during Period 1 Afatinib 40 mg/day + Paclitaxel 80mg/kg/3w during Period 2
干预措施: Afatinib (Drug)
Open label
Afatinib 40 mg/day during Period 1 Afatinib 40 mg/day + Paclitaxel 80mg/kg/3w during Period 2
干预措施: Paclitaxel (Drug)
结局指标
主要结局
Response rate
时间窗: 6 weeks
Incidence and intensity of adverse events
时间窗: 4 weeks
次要结局
- Disease control rate(6 weeks)
- Progression free survival(6 weeks)
- Overall survival(6 weeks)
研究者
Dr. Lore Decoster
Coordinator Investigator
AZ-VUB