An Investigator Initiated Phase 1 Trial To Evaluate mFOLFOX6 With Selinexor (KPT-330), An Oral Selective Inhibitor Of Nuclear Export (SINE), In Patients With Metastatic Colorectal Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Numbers of Patients With Dose Limiting Toxicities
研究概览
简要总结
This trial will evaluate the combination treatment of established chemotherapy regimen mFOLFOX6 with Selinexor, an oral Selective Inhibitor Of Nuclear Export, in patients with metastatic Colorectal Cancer. The purpose is to determine the maximum tolerated dose (MTD) of selinexor in combination with mFOLFOX6.
详细描述
This was a multi center, open-label, non-randomized phase I trial study to determine the MTD of a combination of mFOLFOX6 (Folinic Acid (Leucovorin)-Fluorouracil-Oxaliplatin) and selinexor in patients with metastatic colorectal cancer.
After screening and registration in the study, all enrolled patients were to be treated with oxaliplatin (85 mg/m² IV over 2 hours, Day 1), 5-FU (5-Fluorouracil 400 mg/m2 IV bolus, Day 1), leukovorin (400 mg/m2 IV over 2 hours, Day 1), and 5-FU (2,400 mg/m² continuous infusion, Days 1-3) every 2 weeks and escalating doses of selinexor as follows:
Patients in Dose Level 1 were to receive oral selinexor 40 mg on day 1, 3, and 8.
Patients in Dose Level 2 were to receive oral selinexor 60 mg on day 1, 3, and 8.
Patients in Dose Level 3 were to receive oral selinexor 80 mg on day 1, 3, and 8.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 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
- •Patients with histologically confirmed diagnosis of colorectal cancer presenting with unresectable stage IV (UICC) disease (primary tumor may be present)
- •Patients who are feasible for treatment with FOLFOX (prior adjuvant or palliative treatment is allowed)
- •ECOG (Eastern Cooperative Oncology Group) Performance status ≤ 1
- •Life expectancy > 3 months
- •Age ≥18 years
- •Haematologic function as follows (5% deviation allowed):
- •Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- •platelets ≥ 100 x109/L
- •hemoglobin ≥ 9 g/dl or 5.59 mmol/l
- •Adequate liver function as follows (10% deviation allowed)
- •serum alanine transaminase (ALT) ≤ 2.5 x ULN (in case of liver metastases < 5 x ULN)
- •total bilirubin ≤ 1.5 x ULN (patients with Gilbert's syndrome total bilirubin ≤2.5 x ULN)
- •Adequate renal function as follows (10% deviation allowed)
- •· creatinine ≤ 1.5 x ULN
- •Signed written informed consent
- •Women of child-bearing potential must have a negative pregnancy test
排除标准
- •adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy;
- •Treatment with any systemic anticancer therapy ≤ 3 weeks prior to cycle 1 day 1
- •Uncontrolled active infection (Hepatitis B and C infection are NOT exclusion criteria) and/or known HIV infection;
- •Renal failure requiring haemodialysis or peritoneal dialysis;
- •Patients who are pregnant or breast-feeding;
- •Patients with significantly diseased or obstructed gastrointestinal tract, malabsorption, uncontrolled vomiting or diarrhea resulting in inability to swallow oral medications;
- •Presence of symptomatic Central nervous system (CNS) metastasis
- •Unresolved toxicity from previous anti-cancer therapy or incomplete recovery from surgery, in particular oxaliplatin-induced peripheral neuropathy > grade
- •Any of the following within the 12 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis, or other thromboembolic event.
研究组 & 干预措施
Selinexor + mFOLFOX6
Different Dose Levels of Selinexor will be evaluated in combination with mFOLFOX6 (see interventions)
干预措施: Selinexor (Drug)
Selinexor + mFOLFOX6
Different Dose Levels of Selinexor will be evaluated in combination with mFOLFOX6 (see interventions)
干预措施: Oxaliplatin (Drug)
Selinexor + mFOLFOX6
Different Dose Levels of Selinexor will be evaluated in combination with mFOLFOX6 (see interventions)
干预措施: 5-FU (Drug)
Selinexor + mFOLFOX6
Different Dose Levels of Selinexor will be evaluated in combination with mFOLFOX6 (see interventions)
干预措施: Folinic Acid (Drug)
结局指标
主要结局
Numbers of Patients With Dose Limiting Toxicities
时间窗: 28 days of treatment
Primary objective is the determination of the maximum tolerated dose (MTD) of selinexor in combination with mFOLFOX6 in patients with metastatic colorectal cancer. Criteria to assess MTD was the experience of AEs \> grade 3, discontinuation from study treatment due to adverse events or withdrawal of consent by the patients.
次要结局
- Overall Response Rate(2 years)
- Progression Free Survival (PFS)(2 years)
- Number of Patients Experiencing Adverse Events(treatment start to up to 30 days after last dose)
- Number of Patients Still Alive at End of Study (Overall Survival)(2 years)