Phase II Trial of Sorafenib in Combination With Modified FOLFOX in Patients With Advanced Hepatocellular Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 3
- 主要终点
- Time to Progression
研究概览
简要总结
This research study is a Phase II clinical trial. Phase II clinical trials test the effectiveness of an investigational combination of drugs to learn whether the drug combination works in treating a specific cancer. "Investigational" means that the modified FOLFOX and sorafenib combination is still being studied and that research doctors are trying find out more about it-such as the safest dose to use, the side effects it may cause, and if the combination is effective for treating different types of cancer. It also means that the FDA has not yet approved the modified FOLFOX and sorafenib combination that will be used in this study for liver cancer.
FOLFOX is a combination of three drugs: folinic acid (leucovorin), fluorouracil (5-FU), and oxaliplatin. The dosage amounts for some of these FDA approved drugs will be modified slightly in this study. The FOLFOX combination is approved by the FDA and is a standard treatment of colorectal cancer. However, it is not approved for the treatment of liver cancer.
Sorafenib is a new drug, which is approved under the brand name Nexavar for the treatment of liver cancer. It is also currently being tested in various other cancers. Sorafenib works by slowing down and/or stopping the development of new cancer cells and new blood vessels. By slowing down and/or stopping the growth of new blood vessels around a tumor, it is believed that sorafenib prevents or slows down the growth of tumors.
In this research study, sorafenib, the standard treatment, is being combined with modified FOLFOX, which has shown some antitumor activity in liver cancer.
详细描述
After agreeing to participate in this study, the patient will be asked to undergo some screening tests or procedures to find out if he/she is eligible. Many of these tests and procedures are likely to be part of regular cancer care and may be done even if it turns out that the patient does not take part in the research study. If the patient has had some of these tests or procedures recently, they may or may not have to be repeated. These tests and procedures include: a medical history, physical exam, performance status, electrocardiogram, assessment of tumor, blood tests, urine test, pregnancy test and optional research biopsy. If these tests show that the patient is eligible to participate in the research study, he/she will begin the study treatment. If the patient does not meet the eligibility criteria, he/she will not be able to participate.
If the patient takes part in this research study, he/she will be given a sorafenib study drug-dosing diary for each treatment cycle. Each treatment cycle lasts 28 days (4 weeks), during which time the patient will be taking the study drug twice daily. The diary will also include special instructions for sorafenib.
There will be a 2-week Lead-in period, in which the patient will receive sorafenib alone for the first two weeks of the study. Cycle 1 will begin once the patient receives the combination sorafenib and FOLFOX.
For FOLFOX, all three chemotherapy drugs will be injected through a central vein in the patient's chest (portacath) and will be given once every two weeks (14 days), starting on Day 15 of Cycle 1. The patient will receive oxaliplatin first as a 2-hour infusion, followed by leucovorin, and then 5-FU. The 5-FU infusion can last up to 46 hours and will be given through a small portable pump. The investigator will ask the patient to come back to the clinic on day 3 (46 hours after begin 5-FU dose) for pump discontinuance.
During all cycles the patient will have a physical exam and the patient will be asked questions about his/her general health and specific questions about any problems that he/she might be having and any medication he/she may be taking.
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 confirmed advanced HCC
- •Barcelona Clinic Liver Cancer stage C or stage B if you cannot tolerate or failed TACE
- •No cirrhosis or Child-Pugh A cirrhosis
- •Measurable lesions
- •All acute toxic effects of any prior treatment have resolved to NCI-CTCAE v4.0 grade 1 or less
- •Able to swallow and retain oral medication
排除标准
- •Prior systemic regimens for HCC
- •Uncontrolled hypertension
- •CLIP score > 3
- •ECOG PS > 1
- •Clinically apparent central nervous system metastases or carcinomatous meningitis
- •Pregnant or breastfeeding
- •Active or clinically significant cardiac disease
- •Evidence or history of bleeding diathesis or coagulopathy
- •Any pulmonary hemorrhage/bleeding event of NCI-CTCAE v4.0 Grade 2 or higher within 4 weeks of enrollment
- •Presence of a non-healing wound, non-healing ulcer, or bone fracture
- •History of organ allograft
- •Any malabsorption condition
- •Medical or psychiatric condition that constitutes an unacceptable risk for participation in this trial
- •Have received another investigational agent within 4 weeks of first dose of sorafenib
- •Previously untreated or concurrent cancer except those treated more than 3 years ago
- •History of other disease, metabolic dysfunction, physical examination finding or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the subject at high risk from treatment complications
- •QTC>500msec or history of uncontrolled angina, arrhythmias, or congestive heart failure
- •Concurrent systemic and local anti-cancer therapy
- •Prior use of sorafenib, oxaliplatin or 5FU
- •Major surgery within 30 days
- •Concurrent use of aspirin>100mg
- •Therapeutic anticoagulation with vitamin K antagonists or with heparins or heparinoids
研究组 & 干预措施
Experimental Treatment Arm
FOLFOX (Leucovorin, Fluorouracil and Oxaliplatin) + Sorafenib Sorafenib: orally, twice daily FOLFOX: injected via portacath once every two weeks
干预措施: Leucovorin (Drug)
Experimental Treatment Arm
FOLFOX (Leucovorin, Fluorouracil and Oxaliplatin) + Sorafenib Sorafenib: orally, twice daily FOLFOX: injected via portacath once every two weeks
干预措施: Fluorouracil (Drug)
Experimental Treatment Arm
FOLFOX (Leucovorin, Fluorouracil and Oxaliplatin) + Sorafenib Sorafenib: orally, twice daily FOLFOX: injected via portacath once every two weeks
干预措施: Oxaliplatin (Drug)
Experimental Treatment Arm
FOLFOX (Leucovorin, Fluorouracil and Oxaliplatin) + Sorafenib Sorafenib: orally, twice daily FOLFOX: injected via portacath once every two weeks
干预措施: Sorafenib (Drug)
结局指标
主要结局
Time to Progression
时间窗: The amount of time from registration until disease progression or death, median duration 7.7 months
The median amount of time from the time of registration until disease progression. Disease progression was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
次要结局
- Median Progression Free Survival(From the start of treatment until disease progression or death, median duration of 232 days)
- Number of Patients Experiencing Adverse Events(From the start of treatment until 30 days after the end of treatment, median duration of 10.7 months)
- Median Overall Survival(From registration until death, median duration of 15.1 months)
- Overall Response Rate(2 years)
- Duration of Response(From the time of treatment response until death or disease progression (median duration 172 days))
研究者
Goyal, Lipika
Prinicipal Investigator
Massachusetts General Hospital