Comparison Study of Sorafenib and 5-fluorouracil/Mitomycin for Metastatic Hepatocellular Carcinoma
An Open Label, Phase 2 Trial Comparing Sorafenib and 5-fluorouracil/Mitomycin in Hepatocellular Carcinoma With Pulmonary Metastasis
調査の概要
詳細な説明
Most HCC patients are diagnosed at advanced stages in Korea, but effective treatment strategies for advanced HCC have not been established. In particular, optimal treatment strategy for extrahepatic as well as intrahepatic recurrences following locoregional therapy (e.g., transarterial chemoembolization, radiofrequency ablation therapy, and percutaneous ethanol injection) is still a challenging issue. Extrahepatic metastasis has been encountered more frequently, being more problematic than before in the management of HCC due to the increased survival with effective locoregional treatments. The lung is the most common site of extrahepatic metastasis and the surgical resection of pulmonary metastatic lesions may result in improved survival in selected patients. Previous studies suggested that aggressive management including resection of the extrahepatic recurrence combined with locoregional therapy for intrahepatic HCC may offer long-term survival in selected patients with recurrent HCC following hepatectomy. Such an aggressive strategy has serious limitation in clinical practice in that extrahepatic recurrence usually present as multiple lesions. Systemic chemotherapy has been one of the most commonly used treatment modalities for patients with multiple extrahepatic metastasis. However, chemotherapy using either a single or combined cytotoxic agents provides only limited benefit for such patients. The aim of this study is to compare the efficacy of sorafenib to 5-fluorouracil/mitomycin in HCC patients with pulmonary metastasis whose intrahepatic tumors had been previously controlled with repeated locoregional therapies before the initiation of systemic chemotherapy.
Outline:
- Experimental arm(the FM group): Patients receive 5-FU IV continuously over 10 hours on day 1~6 and mitomycin IV push on day 1~4. Treatment repeats every 28 days.
- Active Comparator arm(the sorafenib group): Patients will receive 2 tablets of sorafenib (200 mg/tablet) twice daily, orally on a continuous basis.
In all arms, treatment continues in the absence of disease progression or unacceptable toxicity. During the treatment period, patients will have study visits on Day 1 of every cycle (every 4 weeks from start of study drug) and will receive CT/MRI assessment every 2 cycles (every 8 weeks). In the event of radiological progression confined to the liver, e.g. appearance of new nodules in the liver in areas previously not treated by locoregional therapies, patients will then also be treated with locoregional therapies such as TACE or local ablation as long as the they may still benefit from treatment. If patients are no longer amenable to locoregional therapies (in the case of untreatable progression), the study will be stopped and best supportive care be offered. This will be based on the investigator's clinical judgment of the subject's status.
研究の種類
入学 (実際)
段階
- フェーズ2
連絡先と場所
研究場所
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Seoul、大韓民国
- Seoul National University Hospital
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
- Patients with clinical or histological diagnosis of HCC based on the guidelines of the AJCC
- Patients with at least one, bi-dimensionally measurable, pulmonary metastasis without intrahepatic viable tumor (Viable tumor is defined as uptake of contrast agent in the arterial phase of dynamic CT or MRI.)
- Patients who have received previous local therapy treatments (RFA, PEI, cryoablation, surgery, resection) to non-target lesions are eligible
- Age : 20 years to 80 years
- ECOG Performance Status of 0 to 1
- Child-Pugh class A or B (Child-Pugh score 7)
Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening:
- Hb ≧ 9 g/dL
- Absolute neutrophil count > 1000/mm3
- Platelet count ≧ 60,000 /mm3
- Adequate clotting function: INR < 1.5
- Hepatic: AST and ALT < 5 X ULN
- Renal: serum creatinine < 1.7mg/dL
- Bilirubin ≦ 3 mg/dL
Exclusion Criteria:
- Patients with diffuse infiltrative type of HCC that are poorly defined
- Presence of hepatic encephalopathy and intractable ascites
- Patients who are on a liver transplant list
- The patient has received prior systemic chemotherapy
- History of organ allograft
- Active clinically serious infections (> grade 2 NCI-CTC version 3.0), including spontaneous bacterial peritonitis
- History of cardiac disease: congestive heart failure > NYHA class 2; active coronary artery disease (myocardial infarction more than 6 months prior to study entry is allowed), cardiac arrhythmias requiring anti-arrhythmic therapy or uncontrolled hypertension and diabetes mellitus
- Previous or concurrent cancer that is distinct in primary site or histology from HCC, EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis & T1). Any cancer curatively treated > 3 years prior to entry is permitted
- HIV infection or AIDS-related illness or serious acute or chronic illness (based on medical history)
研究計画
研究はどのように設計されていますか?
デザインの詳細
- 主な目的:処理
- 割り当て:非ランダム化
- 介入モデル:並列代入
- マスキング:なし(オープンラベル)
武器と介入
参加者グループ / アーム |
介入・治療 |
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実験的:The FM group
Patients in the FM group will be administered 5-FU plus mitomycin
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15mg/kg/day continuous IV from day 1 to day 6 every 28 days.
他の名前:
4mg/day IV push from day 1 to day 4 every 28 days
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アクティブコンパレータ:The sorafenib group
Patients in the sorafenib group will be administered sorafenib
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400 mg BID every 28 days
他の名前:
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この研究は何を測定していますか?
主要な結果の測定
結果測定 |
時間枠 |
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Progression free survival (PFS)
時間枠:every 8 weeks
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every 8 weeks
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二次結果の測定
結果測定 |
時間枠 |
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Time-to-progression (TTP)
時間枠:every 8 weeks
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every 8 weeks
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Objective tumor response rate
時間枠:Determined by CT scan at the end of every 2 cycles until progressive disease is documented or intolerable toxicity occurs
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Determined by CT scan at the end of every 2 cycles until progressive disease is documented or intolerable toxicity occurs
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Adverse event rates and the toxicities
時間枠:every 4 weeks
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every 4 weeks
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Overall survival
時間枠:every 8 weeks
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every 8 weeks
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協力者と研究者
研究記録日
主要日程の研究
研究開始
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。
5-FUの臨床試験
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Hamamatsu University完了
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University of Alabama at BirminghamNational Cancer Institute (NCI); Glaxo Wellcome完了
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University Medical Center GroningenAmsterdam UMC, location VUmc完了
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Ralf HofheinzInstitut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest; Deutsche Krebshilfe... と他の協力者募集
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Sol-Gel Technologies, Ltd.完了
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Chia Tai Tianqing Pharmaceutical Group Co., Ltd.わからない