NCT02448290已完成2 期
Phase II, Single-arm Study of Selumetinib in Combination With Docetaxel, in Advanced Gastric Adenocarcinoma Patients With Low/High MEK Signature, RAS Mutation or RAS Amplification as a Second-line Chemotherapy
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- response rate
研究概览
简要总结
This study is a single-arm, phase II study of selumetinib in combination with docetaxel in patients with advanced gastric adenocarcinoma harboring MEK signature, RAS mutation or amplification as a second line chemotherapy.
Selumetinib will be administered orally 75mg twice a day continuously. Docetaxel will be administered as an IV infusion over 1 hour at 60 mg/m2 every 3 week of a 21 days schedule.
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
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Provision of fully informed consent prior to any study specific procedures.
- •Patients must be ≥20 years of age.
- •Advanced gastric adenocarcinoma (including GEJ) that has progressed during or after firstline therapy.
- •The 1st line regimen must have contained doublet 5-fluoropyrimidine and platinum based regimen.
- •Relapse within 6 months of completion of adjuvant/neoadjuvant chemotherapy containing doublet 5-fluoropyrimidine and platinum-based regimen could be considered as 1st line therapy.
- •Previous adjuvant/neoadjuvant chemotherapy is allowed, if completed more than 6 months prior to starting the 1st line therapy.
- •Provision of tumor sample (from either a resection or biopsy)
- •Patients with MEK signature, RAS mutation or amplification through the VIKTORY trial.
- •(The VIKTORY trial uses Ion Torrent PGM to screen for a panel of cancer mutations and nanostring, copy number variation panel (see addendum for the VIKTORY trial)
- •Patients are willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
- •ECOG performance status 0-
- •Patients must have a life expectancy ≥ 3 months from proposed first dose date.
- •Patients must have acceptable bone marrow, liver and renal function measured within 28 days prior to administration of study treatment as defined below:
- •Haemoglobin ≥9.0 g/L (transfusion allowed)
- •Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- •White blood cells (WBC) > 3 x 109/L
- •Platelet count ≥100 x 109/L (transfusion allowed)
- •Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (does not include patients with Glibert's disease)
- •AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present in which case it must be ≤ 5x ULN
- •Serum creatinine ≤1.5 x institutional ULN
- •At least one measurable lesion that can be accurately assessed by imaging or physical examination at baseline and following up visits.
- •Negative urine or serum pregnancy test within 28 days of study treatment, confirmed prior to treatment on day
- •for women of childbearing potential.
- •Provision of consent for mandatory biopsy at progression
排除标准
- •More than one prior chemotherapy regimen (except for adjuvant/neoadjuvant chemotherapy with more than 6 month wash out period) for the treatment of gastric cancer in the advanced setting.
- •Any previous treatment with MEK, RAS or RAF inhibitors
- •Any previous treatment with docetaxel.
- •Patients with second primary cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for ≤5 years.
- •HER2 positive patients (defined by HER2 3+ by immunohistochemistry or HER2 SISH +)
- •Patients unable to swallow orally administered medication.
- •Treatment with any investigational product during the last 14 days before the enrollment (or a longer period depending on the defined characteristics of the agents used).
- •Patients receiving any systemic chemotherapy, radiotherapy (except for palliative reasons), within 3 weeks from the last dose prior to study treatment (or a longer period depending on the defined characteristics of the agents used). The patient can receive a stable dose of bisphosphonates or denusomab for bone metastases, before and during the study as long as these were started at least 4 weeks prior to treatment.
- •Concomitant use of known potent CYP3A4 inhibitors such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir.
- •With the exception of alopecia, any ongoing toxicities (>CTCAE grade 1) caused by previous cancer therapy.
- •Intestinal obstruction or CTCAE grade 3 or grade 4 upper GI bleeding within 4 weeks before the enrollment.
- •Resting ECG with measurable QTcB > 480 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome.
- •Patients with cardiac problem as follows: uncontrolled hypertension (BP ≥150/95 mmHg despite medical therapy) Baseline Left ventricular ejection fraction below the LLN of <55% measured by echocardiography or institution's LLN for MUGA, Atrial fibrillation with a ventricular rate >100 bpm on ECG at rest , Symptomatic heart failure (NYHA grade II-IV), Prior or current cardiomyopathy, Severe valvular heart disease, Uncontrolled angina (Canadian Cardiovascular Society grade II-IV despite medical therapy), Acute coronary syndrome within 6 months prior to starting treatment
- •Ophthalmological conditions as follows:Intra-ocular pressure >21 mmHg, or uncontrolled glaucoma (irrespective of intra-ocular pressure), Current or past history of retinal pigment epithelial detachment/central serous retinopathy or or current or past history retinal vein occlusion
- •Female patients who are breast-feeding or child-bearing and Male or female patients of reproductive potential who are not employing an effective method of contraception
- •Any evidence of severe or uncontrolled systemic disease, active infection, active bleeding diatheses or renal transplant, including any patient known to have hepatitis B, hepatitis C or human immunodeficiency virus (HIV)
研究组 & 干预措施
docetaxel+selumetinib
Experimental
Selumetinib 75 mg will be administered orally twice a day with continuous dosing schedule Docetaxel 60 mg/m2 will be administered via intravenous access every 3 weeks.
干预措施: docetaxel plus selumetinib (Drug)
结局指标
主要结局
response rate
时间窗: 24 weeks
次要结局
- overall survival(up to 100weeks)
- progression-free survival(up to 100weeks)
- duration of response(24 weeks)
- disease control rate(8weeks)
- safety assessed by safety( AEs/SAEs)(up to 100weeks)
研究者
Jeeyun Lee
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center,
Samsung Medical Center
研究点 (1)
Loading locations...
相似试验
进行中（未招募）
3 期
Assess Efficacy & Safety of Selumetinib in Combination With Docetaxel in Patients Receiving 2nd Line Treatment for v-Ki-ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) Positive NSCLCLocally Advanced or Metastatic Non Small Cell Lung Cancer Stage IIIb - IVNCT01933932AstraZeneca510
已完成
2 期
Phase II Study on Sintilimab Combined With Docetaxel for Chemotherapy Failure Advanced NSCLC: the SUCCESS StudyNon-small Cell Lung CancerNCT03798743Hunan Province Tumor Hospital30
Unknown
2 期
Docetaxel and S-1 Combination Therapy as Second-line Treatment for Advanced Gastric CancerAdvanced Gastric CancerNCT03137004Fujian Cancer Hospital47
终止
2 期
Selumetinib in Treating Patients With Relapsed or Refractory Diffuse Large B-cell LymphomaRecurrent Adult Diffuse Large Cell LymphomaNCT01278615National Cancer Institute (NCI)16
终止
2 期
Docetaxel and Lapatinib in Metastatic Transitional Cell Carcinoma in BladderRecurrent Bladder CancerStage III Bladder CancerStage IV Bladder CancerTransitional Cell Carcinoma of the BladderNCT01382706University of Southern California15