the Effect of Grazoprevir/Elbasvir and TACE vs. TACE Alone in Prolonging Survival of Patients With Non-resectable HCV Associated HCC. (ZEPATIER)
2017年4月11日 更新者：michal roll、Tel-Aviv Sourasky Medical Center
Pilot Study to Assess the Effect of Grazoprevir/Elbasvir (ZEPATIER™) and Transarterial Chemoembolization (TACE) vs. TACE Alone in Prolonging Survival of Patients With Non-resectable HCV Associated Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second leading cause of cancer-related deaths in the world.
Hepatitis C virus (HCV) is the most common underlying cause of cirrhosis and HCC in the western world.
Most patients with HCC present with either non-resectable tumor and/or severe underlying liver dysfunction, and are not suitable candidates for curative treatments by resection or transplantation.
Thus, for the majority of patients with HCV related HCC, the only option is prolongation of life without a chance for cure.
These patients generally have a poor prognosis with a median survival of less than 1 year.
Arterial obstruction of branches of the hepatic artery and simultaneous infusion of chemotherapy (Trans-arterial chemo-embolization or TACE) induces ischemic tumor necrosis with a high rate of objective tumor responses (30-60%).
Overall, the median survival after TACE for intermediate HCC is about 20 months, an improvement over supportive care.
Treatment with Grazoprevir/Elbasvir showed excellent results in phase 3 studies for patients with HCV genotype 1 (a and b) and genotype 4 infection and is approved for HCV treatment in the USA, Europe and Israel.
Anti-HCV therapies may influence HCC biology by decreasing inflammation and may thus alter the tumor microenvironment.
調査の概要
状態
わからない
条件
詳細な説明
Single center, open label, prospective pilot study.
The study will include 20 HCV genotype 1 (a and b) cirrhotic patients (Child Pugh A compensated cirrhosis) with advanced, un-resectable HCC who are eligible for TACE.
This pilot study will have one arm which will be compared to historical controls.
All patients participating in the study will receive Grazoprevir/Elbasvir treatment according to established guidelines together with regular TACE treatments.
The historical controls will refer to patients who received regular TACE treatments alone (standard of HCC care).
Follow up will be for up to 24 months from TACE initiation.
研究の種類
介入
入学 (予想される)
20
段階
- 適用できない
参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年～75年 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
Inclusion Criteria:
- Patients with chronic HCV genotype 1 (a and b) infection and un-resectable HCC who are eligible for TACE
- Ages 18-75 years
- Willing to take part in a clinical trial and have signed an informed consent
- Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or less
- Child-Pugh liver function class A
- Patients with expected survival of less than 1 year
- Adequate hematologic function (plt≥60, 000 /L; Hb≥8.5 g/dl; and INR≤1.7
- Adequate hepatic function (albumin ≥3.5 g/dl; total bilirubin, ≤2 mg/dl; ALT and AST ≤5 times the upper limit of the normal range)
- Adequate renal function (serum creatinine ≤1.5 times the upper limit of normal range).
Exclusion Criteria:
- Patients unwilling to sign the informed consent
- Patients unwilling or not capable to complete the anti-viral treatment with Grazoprevir/Elbasvir
- CPT score >7
- Patients ineligible for TACE
- Patients with contraindications to elbasvir/grazoprevir
- Patients suffering from other underlying liver disease (HBV, HIV, PSC, PBC, AIH etc.)
- Patients with malignancies other than HCC
- Patients with previous anti-HCC treatment (RFA, TACE, SIRT or sorafenib)
- Active alcohol or substance use
- Previous liver transplantations
- Child Pugh B or C cirrhosis
- Total serum bilirubin >1.9 mg/dL
- Extra-hepatic spread (metastases)
- Pregnant/lactating women, minors and disabled/incapacitated persons
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
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：なし
- 介入モデル：単一グループの割り当て
- 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 |
|---|---|
|
実験的：HCV patients with un-resectable HCC
HCV genotype 1 (a and b) cirrhotic patients (child pugh A compensated cirrhosis) with advanced and un-resectable HCC who are eligible for TACE . The patients will receive Grazoprevir/Elbasvir and Transarterial Chemoembolization. Their outcomes will be compared to the medical records of patients who underwent Transarterial Chemoembolization only, in the past. |
anti-viral treatment for HCV
Medical records of patients who underwent Transarterial Chemoembolization only, in the past.
A minimally invasive procedure performed in interventional radiology to restrict a tumor's blood supply.
Small embolic particles coated with chemotherapeutic drugs are injected selectively through a catheter into an artery directly supplying the tumor.
These particles both block the blood supply and induce cytotoxicity, attacking the tumor in several ways.
|
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 |
|---|---|---|
|
Overall survival
時間枠：assessed up to 24 months
|
15% or more increase in survival with the combination treatment of Grazoprevir/Elbasvir and TACE vs. historical control of TACE alone; Time Frame: from start of treatment to death from any cause, or last known date of survival
|
assessed up to 24 months
|
|
Adverse events and serious adverse events (AEs, SAEs)
時間枠：24 months
|
will be assessed in all patients receiving at least one dose of a combination therapy, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
|
24 months
|
|
Time to progression (TTP)
時間枠：Assessed, up to 24 months
|
Time from start of treatment until the first documented event of symptomatic progression.
|
Assessed, up to 24 months
|
|
SVR12 rates
時間枠：12 weeks after the last actual dose of Grazoprevir/Elbasvir
|
: proportion of patients achieving SVR12
|
12 weeks after the last actual dose of Grazoprevir/Elbasvir
|
|
Hepatic de-compensation as assessed by clinical end-points
時間枠：Once a month up to 24 months
|
development of ascites, and will undergo repeated liver function tests every 2 weeks to detect CPT increase.
|
Once a month up to 24 months
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Time to radiologic progression
時間枠：The time from start of treatment to disease progression, according to mRECIST, assessed up to 24 months.
|
a decrease in tumor in 15 % or more of the patients undergoing combination therapy vs. historical control of TACE alone
|
The time from start of treatment to disease progression, according to mRECIST, assessed up to 24 months.
|
|
Disease-control rate
時間枠：at least 28 days after the first demonstration of that rating on the basis of independent radiologic review
|
The percentage of patients who had a best-response rating of complete response, partial response, or stable disease (according to mRECIST) that was maintained for at least 28 days after the first demonstration of that rating on the basis of independent radiologic review
|
at least 28 days after the first demonstration of that rating on the basis of independent radiologic review
|
|
decrease in tumor markers
時間枠：Screening and 24 months.
|
A 50 % decrease in tumor markers in 15 % or more patients undergoing combination therapy vs. TACE alone
|
Screening and 24 months.
|
|
quality of life
時間枠：At screening, and months 3,13,22.
|
Assess quality of life as measured by SF-36 questionnaire
|
At screening, and months 3,13,22.
|
|
Symptom severity score
時間枠：At screening, and months 3,13,22.
|
Assess severity of symptoms as measured by FSHI8 questionnaire
|
At screening, and months 3,13,22.
|
協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (予想される)
2017年5月1日
一次修了 (予想される)
2018年5月1日
研究の完了 (予想される)
2019年5月1日
試験登録日
最初に提出
2017年2月8日
QC基準を満たした最初の提出物
2017年4月11日
最初の投稿 (実際)
2017年4月12日
学習記録の更新
投稿された最後の更新 (実際)
2017年4月12日
QC基準を満たした最後の更新が送信されました
2017年4月11日
最終確認日
2017年4月1日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- TASMC-16-OS-0702-CTIL
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
いいえ
米国FDA規制機器製品の研究
いいえ
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。
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