Open-label, Single Arm, Two-stage Study, Evaluating the Efficacy and Safety of Bimiralisib in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinomas (HNSCC) Harboring NOTCH1 Loss of Function (LOF) Mutations
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
Preclinical data and limited clinical evidence suggest that Head and Neck Squameous Cell Carcinoma tumors harboring certain mutations may respond well to PI3K/mTOR inhibition (phosphatidylinositol-3-kinase/ mammalian target of rapamycin inhibition).
The current study enrolls patients with refractory and / or metastatic Head and Neck Squameous Cell Carcinoma based on the mutational status of their disease to assess the response to treatment with bimiralisib, an orally available pan-PI3K/mTOR inhibitor (phosphatidylinositol-3-kinase/ mammalian target of rapamycin inhibitor).
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
- •Histologically or cytological confirmed diagnosis of Head and Neck Squameous Cell Carcinoma, for which no standard curative or life prolonging therapy is available
- •Available CLIA-certified sequencing results of the NOTCH gene in Head and Neck Squameous Cell Carcinoma (HNSCC) tumor material. The tumor must harbor a NOTCH1 LOF mutation as confirmed by central review (MD Anderson Cancer Center, MDACC)
- •ECOG performance status of ≤ 2
- •Adequate bone marrow, liver, and renal functions
- •Measurable disease according to RECIST version 1.1
- •Patients of reproductive potential must agree to use effective contraception from screening until 90 days after discontinuing study treatment.
排除标准
- •Has received any anti-cancer treatment including hormonal and investigational agents within 21 days prior to first dose of bimiralisib.
- •Major surgery within 28 days prior to first dose of bimiralisib or persisting side effects that have not improved to NCI-CTCAE grade 1 or better.
- •Pregnant or nursing (lactating) women.
- •Poorly controlled diabetes mellitus, steroid-induced diabetes mellitus
- •Has other active malignancies that require systemic treatment.
- •Has a known history of HIV infection
- •Any of the following cardiac abnormalities:
- •History of, or current, documented congestive heart failure (New York heart association functional classification iii - iv), documented cardiomyopathy
- •Symptomatic (NYHA class II or higher) left ventricular ejection fraction (LVEF) < 40% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (echo)
- •Myocardial infarction ≤ 6 months prior to enrolment
- •Unstable angina pectoris
- •Serious uncontrolled cardiac arrhythmia
- •Symptomatic pericarditis
- •Impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug.
- •Patient has a history of non-compliance to medical regimen or inability to grant consent.
- •Medically documented history of an active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others) or ≥ CTCAE grade 3 anxiety
- •History of interstitial pneumonitis or patients who require chronic oxygen supplementation.
研究组 & 干预措施
Open single arm
Bimiralisib capsules orally
干预措施: Bimiralisib (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: At 6 and 12 weeks after the start of therapy (± 3 days)
Radiological tumor assessments were performed by computed tomography (CT) or magnetic resonance imaging (MRI) according to a standard protocol. ORR: comprised of all patients who achieved a confirmed partial or a confirmed complete response per RECIST 1.1
次要结局
未报告次要终点