Recurrence Rate of Hepatocellular Carcinoma After Treatment of Chronic Hepatits C Patients With Direct Acting Antivirals: Randomized Controlled Phase 3 Trial

NCT03551444 | Unknown Phase 3

• 1 other identifier: MD353/2017
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

• Unexpected results were published in 2016 showed increased aggressiveness and rates of HCC recurrence after curative treatment of HCC in HCV patients treated by DAAs achieving SVR. On the other hand, the retrospective analysis of ANRS study, did not observe an increased risk of HCC recurrence after DAAs treatment in patients who underwent curative HCC treatment.
• Assess the recurrence rate of HCC in HCV infected patients with prior history of treated HCC who achieved rCR with and without administration of DAAs and assess the effect of its timing.

Conditions

Hepatocellular Carcinoma; Hepatitis C, Chronic

Outcome Measures

Primary Outcomes (1)

• Recurrence rate

  To compare the Recurrence Rate of HCC in the two main randomized arms (administration of DAAs "arm 1" and control arm "arm 2")

  Follow up will be done from baseline for up to 24 months for detection of sustained HCC treatment,tumoral progression or denovo occurrence

Secondary Outcomes (2)

• effect of timing of administration of DAAs after achieving rCR as regard recurrence rate

  Follow up will be done from baseline for up to 24 months

• Identifications of predictive factors of HCC recurrence

  Follow up will be done from baseline for up to 24 months

Study Arms (2)

Administration of DAA-based treatment (Arm 1)

ACTIVE COMPARATOR

Arm 1 will be divided into 2 groups by randomization according to a 1:1 ratio into: Group A: Administration of DAA-based treatment after 3 months of complete remission of HCC. Group B: Administration of DAA-based treatment after 6 months of complete remission of HCC.

Drug: Administration of DAA-based treatment

Control arm (Arm 2)

EXPERIMENTAL

Not receiving DAAs after complete remission of HCC and to be kept on follow-up

Drug: Administration of DAA-based treatment

Interventions

Administration of DAA-based treatment DRUG

* Antiviral therapy and treatment duration (12/24 weeks) will be indicated in each patient according to the viral genotype/subtype and the severity of liver disease, in accordance with the EASL Recommendations on Treatment of Hepatitis C 2016. * HCV-RNA quantification will be assessed by real-time PCR, with a limit of detection (LOD) of15 IU/mL. * During antiviral treatment, follow-up of the Patients will be monthly by clinical and laboratory evaluation. * Virological response to DAA-based treatment will be assessed by quantitative HCV-RNA at the end of treatment (EOT) and at 4 and 12 weeks after the EOT, to confirm sustained virological response (SVR). * SVR12 is defined as undetectable HCV-RNA at week 12 after the EOT. * Virological failures and early discontinuations of therapy due to adverse events will be also registered.

Administration of DAA-based treatment (Arm 1); Control arm (Arm 2)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: more than or equal to 18 years old.
• Confirmed HCV viremia by PCR.
• CHILD Pugh "A".
• HCC diagnosed by criteria according to AASLD guidelines.
• HCC patients should have been treated prior to randomization by resection, or ablation and achieving rCR.

You may not qualify if:

• Patients below 18 old.
• Patients with advanced liver condition.
• Patients known HBV or HIV infection.
• Prior history of liver transplantation.
• HCC treatment but without rCR before randomization
• Pregnancy and lactation.
• Patients with other malignancies other than HCC.

Sponsors & Collaborators

• Ain Shams University: lead

Study Sites (1)

Ain Shams University

Cairo, Egypt

RECRUITING

Related Publications (7)

• Conti F, Buonfiglioli F, Scuteri A, Crespi C, Bolondi L, Caraceni P, Foschi FG, Lenzi M, Mazzella G, Verucchi G, Andreone P, Brillanti S. Early occurrence and recurrence of hepatocellular carcinoma in HCV-related cirrhosis treated with direct-acting antivirals. J Hepatol. 2016 Oct;65(4):727-733. doi: 10.1016/j.jhep.2016.06.015. Epub 2016 Jun 24.

  PMID: 27349488 BACKGROUND

• Elgharably A, Gomaa AI, Crossey MM, Norsworthy PJ, Waked I, Taylor-Robinson SD. Hepatitis C in Egypt - past, present, and future. Int J Gen Med. 2016 Dec 20;10:1-6. doi: 10.2147/IJGM.S119301. eCollection 2017.

  PMID: 28053553 BACKGROUND

• European Association For The Study Of The Liver; European Organisation For Research And Treatment Of Cancer. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012 Apr;56(4):908-43. doi: 10.1016/j.jhep.2011.12.001. No abstract available.

  PMID: 22424438 BACKGROUND

• European Association for the Study of the Liver. EASL Recommendations on Treatment of Hepatitis C 2016. J Hepatol. 2017 Jan;66(1):153-194. doi: 10.1016/j.jhep.2016.09.001. Epub 2016 Sep 22. No abstract available.

  PMID: 27667367 BACKGROUND

• ANRS collaborative study group on hepatocellular carcinoma (ANRS CO22 HEPATHER, CO12 CirVir and CO23 CUPILT cohorts). Electronic address: stanislas.pol@aphp.fr. Lack of evidence of an effect of direct-acting antivirals on the recurrence of hepatocellular carcinoma: Data from three ANRS cohorts. J Hepatol. 2016 Oct;65(4):734-740. doi: 10.1016/j.jhep.2016.05.045. Epub 2016 Jun 7.

  PMID: 27288051 BACKGROUND

• Nault JC, Colombo M. Hepatocellular carcinoma and direct acting antiviral treatments: Controversy after the revolution. J Hepatol. 2016 Oct;65(4):663-665. doi: 10.1016/j.jhep.2016.07.004. Epub 2016 Jul 12. No abstract available.

  PMID: 27417216 BACKGROUND

• Torres HA, Vauthey JN, Economides MP, Mahale P, Kaseb A. Hepatocellular carcinoma recurrence after treatment with direct-acting antivirals: First, do no harm by withdrawing treatment. J Hepatol. 2016 Oct;65(4):862-864. doi: 10.1016/j.jhep.2016.05.034. Epub 2016 May 30. No abstract available.

  PMID: 27255582 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Hepatitis C, Chronic

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Fatma S Abdelbakey, MD

CONTACT

01033440694; fatma_totta@yahoo.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Ph.D Candidate

Study Record Dates

• First Submitted: May 29, 2018
• First Posted: June 11, 2018
• Study Start: October 1, 2017
• Primary Completion: April 1, 2019
• Study Completion: October 1, 2019
• Last Updated: June 11, 2018

Record last verified: 2018-05

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)