Phase I/II Study of Azacitidine and CAPOX (Capecitabine + Oxaliplatin) in Metastatic Colorectal Cancer Patients Enriched for Hypermethylation of CpG Promoter Islands
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) of Azacitidine, and Capecitabine and Oxaliplatin (CAPOX)
研究概览
简要总结
The goal of the Phase I portion of this study is to find the highest tolerable dose of azacitidine combined with capecitabine and oxaliplatin (CAPOX) that can be given to patients with metastatic colorectal cancer.
The goal of the Phase II portion of this study is to learn if azacitidine, given in combination with CAPOX, can help to control metastatic colorectal cancer. The safety of this drug combination will also be studied.
详细描述
The Study Drugs:
Azacitidine is designed to block certain proteins in cancer cells whose job is to stop the function of the tumor-fighting proteins. By blocking the "bad" proteins, the tumor-fighting genes may be able to work better.
Capecitabine is designed to interfere with the growth of cancer cells.
Oxaliplatin is designed to keep new cancer cells from growing.
Study Groups:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Phase I: Patient must have histologically or cytologically confirmed colorectal adenocarcinoma with metastatic disease documented on diagnostic imaging studies. Disease may be measurable or non-measurable as per RECIST version 1.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- •For patients on full-dose low-molecular weight anticoagulation, no active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or know varices) is allowed.
- •Serum bilirubin levels </= 1.5 times the upper limit of the normal range for the laboratory (ULN)
- •Serum aspartate aminotransferase (AST) or serum alanine aminotransferase (ALT) levels </= 2.5 x ULN and </= 5 x ULN in patients with liver metastases
- •Serum creatinine levels </= 1.5 x ULN
- •Absolute neutrophil count of >/=1,500/mm^3 (ie, >/=1.5 x 10^9/L by International Units [IU]).
- •Platelet count >/=100,000/mm^3 (IU: ≥100 x 10^9/L).
- •Hemoglobin value of >/=9.0 g/dL.
- •No limit to number of prior therapies.
- •Women of childbearing potential must have a negative serum pregnancy test and must be advised to avoid becoming pregnant. Men should be advised to not father a child while receiving treatment. Sexually active women of childbearing potential and men must use an effective method of birth control during the course of the study, in a manner such that risk of failure is minimized.
- •Patient must be refractory to treatment with 5-FU (either intravenous 5-FU or as the oral prodrug, capecitabine) and oxaliplatin, defined as previous clinical or radiographic progression on or within 3 months of treatment with 5-FU and oxaliplatin. There is no limit to the number of prior lines of therapy.
- •Phase II: Patient must have histologically or cytologically confirmed colorectal adenocarcinoma with measurable metastatic disease documented on diagnostic imaging studies by RECIST version 1.1 criteria
- •Phase II: Patient must be known to have CpG island methylator phenotype.
排除标准
- •Patients with known brain metastases or carcinomatous meningitis
- •Patients unable to swallow oral medications or with gastrointestinal disorders that might interfere with proper absorption of oral drugs.
- •Known dihydropyrimidine (DPD) deficiency
- •Grade 3 or more peripheral neuropathy
- •Chemotherapy or any other investigational agents within 14 days of first receipt of study treatment, or major surgery within 28 days of first receipt of study treatment, or palliative radiation within 7 days of first receipt of study treatment.
- •Concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study such as unstable angina, myocardial infarction within 6 months, unstable symptomatic arrhythmia, uncontrolled diabetes, serious active or uncontrolled infection.
- •Known or suspected hypersensitivity to azacitidine or mannitol
- •Pregnant or breast feeding
- •Because of the interaction between coumadin and capecitabine patients taking therapeutic doses of coumarin-derivative anticoagulants, are not eligible. Low-dose Coumadin (e.g. 1 mg PO per day) in patients with in-dwelling venous access devices is allowed but increased frequency of international normalized ratio (INR) monitoring is recommended.
- •Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung.
研究组 & 干预措施
Phase II
MTD of Azacitidine + CAPOX
干预措施: Capecitabine (Drug)
Phase I
Dose Escalation of Azacitidine + CAPOX (Capecitabine, Oxaliplatin)
干预措施: Azacitidine (Drug)
Phase I
Dose Escalation of Azacitidine + CAPOX (Capecitabine, Oxaliplatin)
干预措施: Capecitabine (Drug)
Phase I
Dose Escalation of Azacitidine + CAPOX (Capecitabine, Oxaliplatin)
干预措施: Oxaliplatin (Drug)
Phase II
MTD of Azacitidine + CAPOX
干预措施: Oxaliplatin (Drug)
Phase II
MTD of Azacitidine + CAPOX
干预措施: Azacitidine MTD (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of Azacitidine, and Capecitabine and Oxaliplatin (CAPOX)
时间窗: Up to 3 weeks from the first dose
Dose just below the one at which ≥ 1/3 of subjects experience a dose limiting toxicity (DLT) considered the MTD.
次要结局
- Response Rate of Azacitidine, and Capecitabine and Oxaliplatin (CAPOX)(After 9 weeks (three, 21 day cycles))