Combined Radiotherapy and Sorafenib in Patients With Hepatoma
調査の概要
詳細な説明
Hepatocellular carcinoma (HCC) is a common cause of cancer mortality in Asia. Most patients present with intermediate or advanced disease. Percutaneous ethanol injection, radiofrequency ablation, and transcatheter arterial chemoembolization (TACE) are not considered as a curative treatment and have achieved very limited success in eradicating large HCC. With the development of new radiotherapy (RT) technique, RT can be more safely given to patients with larger tumor burden. Thus, TACE combined with RT has been suggested for treating large HCC. Based on the results of these studies, RT could achieve a tumor response rate of 50 % to 70 %. However, it has not been definitively shown to prolong the overall or disease-free survival due to lack of a phase III clinical trial. In contrast, a retrospective clinical investigation with molecular study suggests that sublethal dose of RT promoted HCC growth outside RT field.
Two phase III trials were shown to be efficacious and well-tolerated in patients with advanced HCC. Median overall survival was significantly 2 to 3 months longer in the sorafenib group than that in the placebo. It is interesting to recognize the combined therapeutic effect of RT with sorafenib. Based on several preclinical experiments, tumor angiogenesis inhibitors seem to be synergistic with irradiation when using before RT, concurrently with RT, or after RT. Thus, we design a single-arm phase II clinical trial to investigate the efficacy of combined RT with sorafenib.
The eligibility criteria are patients with unresectable HCC; good performance status; no prior radiotherapy for the liver; clinical measurable tumor; good liver function and good compliance. After entering this study, the testee will receive RT to hepatic tumor with concurrently sorafenib with a dose of 400 mg twice daily. Hepatic RT will be performed with a daily fraction size of 2.0 to 2.5 Gy to a total dose of 46 Gy to 60 Gy. After RT, maintenance sorafenib with a dose of 400 mg twice daily will be ongoing. Sorafenib will be continued until the occurrence of clinical or radiologic progression, or the occurrence of either unacceptable adverse events or death. Minimum maintenance duration of 6 months is recommended, but not mandatory. The primary end points are response rate and toxicities profile. The secondary endpoints are time to radiological progression interval (TRPI), overall survival, and quality of life assessment.
研究の種類
入学 (予想される)
連絡先と場所
研究連絡先
- 名前：Shang-Wen Chen, MD
- 電話番号：7450 886-4-22052121
- メール：vincent1680616@yahoo.com.tw
研究場所
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Tainan、台湾、600
- 募集
- Chi-Mei Hospital
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コンタクト：
- Li-Ching Lin, MD
- 電話番号：53501 886-6-2812811
- メール：liching51@yahoo.com.tw
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主任研究者：
- Li-Ching Lin, MD
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Taipei、台湾、100
- 募集
- Taipei Medical University Hospital
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コンタクト：
- Jeng-Fong Chiou, MD;PhD
- 電話番号：2130 886-2-27372181
- メール：sjfchiou@xuite.net
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主任研究者：
- Jen-Fong Chiou, MD;PhD
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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
サンプリング方法
調査対象母集団
説明
Inclusion Criteria:
- Patients with unresectable hepatoma with transarterial embolization (TAE) failure or who are not suitable for TAE.
- Age: 20 ~ 69 years.
- ECOG 0 or 1.
- Life expectancy of at least 12 weeks.
- Child-Pugh A or B (preferentially score ≦ 7).
- Cancer of the Liver Italian Program (CLIP) score ≦ 3.
Pretreatment liver function test and renal function test:
- Total bilirubin < 1.5 times the upper limit of normal (ULN)≦ 3.0(ULN)in patients treated by biliary drainage for obstructive jaundice.
- GOP/GPT ≦ 5 X of upper limit of normal range.
- Alkaline phosphatase ≦ 4X of upper limit of normal range.
- Prothrombin time/partial prothrombin time < 1.5 X of ULN.
- Serum Creatinine ≦ 1.0 x ULN.
Pretreatment blood count:
- Hemoglobulin ≧ 9 g/dl.
- Absolute neutrophil count ≧ 1500/mm3.
- Platelet count ≧ 100,000/mm3.
- Subjects with at least one uni-dimensional or bi-dimensional measurable lesion. Lesion must be measured by CT scan or MRI.
- Patients must fully recover from prior therapy that given > 4 weeks before enrolment.11. Signed informed consent must be obtained prior to any study related procedures.
Exclusion Criteria:
- Child-Pugh C
- CLIP score ≧ 4
- Patients with evidence of extrahepatic or metastatic disease
- Patients with evidence of massive ascites
- Patients receiving previous irradiation to liver
- Patients with previous use of Thalidomide less than 6 months from entering of the study
- History of cardiac disease: congestive heart failure >NYHA class 2; active CAD (MI more than 6 mo prior to study entry is allowed); cardiac arrythmias requiring anti-arrythmic therapy (beta blockers or digoxin are permitted)
- Active clinically serious infections ( > grade 2 CTC version 2)
- Patients undergoing renal dialysis
- Patients with evidence or history of bleeding diathesis
- Prior treatment with EGFR TKIs or VEGFR TKIs
- Hypertension uncontrolled by medical therapy
- Symptomatic metastatic brain or meningeal tumors unless the patient is > 6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry. Also the patient must not be undergoing acute steroid therapy or taper.
- Chemotherapy or immunotherapy or other systemic anti-cancer therapy within 4 weeks (6 weeks for nitrosoureas, mitomycin and suramin)
- Major surgery within 4 weeks of start of study
- Concomitant treatment with strong CYP3A4 inducers or inhibitors
- Investigational drug therapy outside of this trial during or within 4 weeks of study entry
- Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment.
- Women of childbearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation, including the 30 days period after last study drug dosing.
- Pregnant or breast-feeding patients
- Known or suspected allergy to the investigational agent or any agent given in association with this trial
- Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors [Ta, Tis & T1] or any cancer curatively treated > 3 years prior to study entry
- Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study
- Patients with seizure disorder requiring medication
- History of organ allograft
- Use of biologic response modifiers, such as G-CSF, within 3 week of study entry
- Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
- Autologous bone marrow transplant or stem cell rescue within 4 months of study
- Patients unable to swallow oral medications
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
コホートと介入
グループ/コホート |
介入・治療 |
|---|---|
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Unresectable hepatoma
Unresectable hepatoma, unsuitable for transarterial embolization or local failure after transarterial embolization
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Radiotherapy: 46 Gy to 60 Gy prescribed to involved hepatic tumor Sorafenib: 2 tablet of sorafenib (200mg) twice daily (totally 800mg per day)
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 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Response rate
時間枠：1-month and 6-month response rate
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1-month and 6-month response rate
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Time-to radiological progression interval
時間枠：2-years
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|
2-years
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協力者と研究者
捜査官
- 主任研究者：Shang-Wen Chen, MD、Department of Radiation Oncology, China Medical University Hospital
研究記録日
主要日程の研究
研究開始
一次修了 (予想される)
研究の完了 (予想される)
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 (見積もり)
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
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