the Effect of Grazoprevir/Elbasvir and TACE vs. TACE Alone in Prolonging Survival of Patients With Non-resectable HCV Associated HCC. (ZEPATIER)
2017년 4월 11일 업데이트: 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.
연구 개요
상태
상태
알려지지 않은
정황
정황
개입 / 치료
개입 / 치료
상세 설명
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.
연구 유형
연구 유형
중재적
등록 (예상)
등록
20
단계
단계
- 해당 없음
참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
자격 기준
공부할 수 있는 나이
18년 (성인, 고령자)
건강한 자원 봉사자를 받아들입니다
아니
연구 대상 성별
모두
설명
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
공부 계획
이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 해당 없음
- 중재 모델: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
팔의 수
1
무기와 개입
참가자 그룹 / 팔참가자 그룹 / 팔 |
개입 / 치료개입 / 치료 |
|---|---|
|
실험적: 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.
|
연구는 무엇을 측정합니까?
주요 결과 측정
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Overall survival
기간: 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)
기간: 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)
기간: 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
기간: 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
기간: 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
|
2차 결과 측정
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Time to radiologic progression
기간: 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
기간: 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
기간: 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
기간: 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
기간: At screening, and months 3,13,22.
|
Assess severity of symptoms as measured by FSHI8 questionnaire
|
At screening, and months 3,13,22.
|
공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
협력자
협력자
연구 기록 날짜
이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.
연구 주요 날짜
연구 시작 (예상)
연구 시작
2017년 5월 1일
기본 완료 (예상)
기본 완료
2018년 5월 1일
연구 완료 (예상)
연구 완료
2019년 5월 1일
연구 등록 날짜
최초 제출
최초 제출
2017년 2월 8일
QC 기준을 충족하는 최초 제출
QC 기준을 충족하는 최초 제출
2017년 4월 11일
처음 게시됨 (실제)
처음 게시됨
2017년 4월 12일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
마지막 업데이트 게시됨
2017년 4월 12일
QC 기준을 충족하는 마지막 업데이트 제출
QC 기준을 충족하는 마지막 업데이트 제출
2017년 4월 11일
마지막으로 확인됨
마지막으로 확인됨
2017년 4월 1일
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
기타 연구 ID 번호
- TASMC-16-OS-0702-CTIL
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
아니
미국 FDA 규제 기기 제품 연구
아니
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