Clinical Trials Logo

Clinical Trial Summary

This phase I/II clinical trial studies the side effects of pembrolizumab with or without elbasvir/grazoprevir and ribavirin and to see how well they work in treating patients with liver cancer that has spread to other places in the body and does not respond to previous treatment. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Elbasvir/grazoprevir and ribavirin may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab in combination with elbasvir/grazoprevir and ribavirin may work better in treating patients with liver cancer than with pembrolizumab alone.


Clinical Trial Description

PRIMARY OBJECTIVES: I. To estimate the tolerability of intravenous (V) administration of pembrolizumab as second-line systemic therapy in subjects with advanced hepatocellular carcinoma. (Arm A and Arm B). II. To evaluate the efficacy of pembrolizumab in combination with elbasvir/grazoprevir (Zepatier) as assessed by the proportion of subjects with hepatitis C virus (HCV) GT1 or GT4 achieving Sustained Virologic Response 12 weeks after the end of all HCV study therapy (SVR12), defined as HCV ribonucleic acid (RNA) below the lower limit of quantitation (LLOQ) (either target detected unquantifiable [TD(u)] or target not detected [TND]) 12 weeks after the end of all study therapy. (Arm B) SECONDARY OBJECTIVES: I. To estimate the objective response rate (ORR), per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 assessed by MD Anderson radiology. II. To estimate the duration of response (DOR), disease control rate (DCR), time to progression (TTP), and progression-free survival (PFS) per RECIST 1.1 assessed by MD Anderson Department of Diagnostic Imaging. III. To evaluate the safety of pembrolizumab in combination with Zepatier as assessed by the proportion of subjects with HCV GT1 or GT4 achieving SVR12 and SVR24, defined as HCV RNA below the LLOQ (either TD[u] or TND) 12 and 24 weeks after the end of all study therapy. EXPLORATORY OBJECTIVES: I. To estimate ORR, DOR, DCR, TTP, PFS and overall survival (OS) per immune response RECIST (irRECIST) as assessed by MD Anderson radiology. II. To explore the relationship between progression on sorafenib versus intolerance of sorafenib and response to pembrolizumab. III. To perform exploratory biomarker research to study the correlation between immunological and molecular changes in tumor tissues and peripheral blood with TTP, OS, and rate of adverse events (AEs). IV. To explore the association between PD-1 ligand (PD-L1) expression by immunohistochemistry (IHC), somatic gene expression profiling (GEP) and antitumor efficacy of pembrolizumab based on RECIST 1.1. V. To explore predictive biomarkers to study the correlation of independent effect of cirrhosis grade and severity of portal hypertension by magnetic resonance imaging (MRI) classification on OS. VI. To explore retrospective risk stratification of the degree of the underlying liver dysfunction by IGF score. To explore retrospective risk stratification of the degree of the underlying liver dysfunction by IGF-1 score. See section 2.1. VII. To assess whether pembrolizumab in combination with Zepatier affects the course of viral infections in subjects with underlying HCV GT1 or GT4. We hypothesize that pembrolizumab in combination with Zepatier will help to reduce viral loads in those with untreated HCV. VIIII. To evaluate the response of HCV GT1 and GT4 to treatment as assessed by sustained virologic response at 4 and 12 weeks after the end of 12 to 16 weeks of pembrolizumab in combination with Zepatier dosing. Sustained virologic response is defined as defined as HCV RNA below the LLOQ (either TD[u] or TND). IX. To evaluate the emergence of viral resistance-associated variants (RAVs) to pembrolizumab in combination with Zepatier in subjects with HCV GT1 or GT4 without RAVs as baseline . X. To evaluate the efficacy of pembrolizumab in combination with Zepatier as assessed by the proportion of subjects with HCV GT1 or GT4 achieving undetectable (TND) HCV RNA and HCV RNA below the LLOQ at Weeks 2, 4, 12 and Follow- Up Week 4 (SVR4), Week 12 (SVR12), and Week 24 (SVR24). XI. To explore the relationship between genetic variation and subject response to the treatment(s) administered. OUTLINE: Patients are assigned to 1 of 2 arms. ARM A: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Cycles repeat every 21 days for up to 35 cycles in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive pembrolizumab as in arm A. Patients also receive elbasvir/grazoprevir orally (PO) once daily (QD) and ribavirin PO QD on days 1-28. Treatment continues for 12-16 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30-90 days and then every 12 weeks. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT02940496
Study type Interventional
Source M.D. Anderson Cancer Center
Contact
Status Completed
Phase Phase 2
Start date December 9, 2016
Completion date August 9, 2023

See also
  Status Clinical Trial Phase
Completed NCT01771653 - Comparison of Two Triple Regimens for Treatment and Retreatment of Chronic Hepatitis C Infection N/A
Recruiting NCT03601546 - Feasibility of Implementing a Cohort of People Living With Hepatitis C in Vietnam
Completed NCT02362217 - A Study to Assess the Safety of HIV and Hep C Vaccine Candidates When Given Separately or in Combination Phase 1
Completed NCT00513461 - Liver Cancer Prevention Trial in Patients With Chronic Hep C Infection Phase 2
Active, not recruiting NCT02143401 - Navitoclax and Sorafenib Tosylate in Treating Patients With Relapsed or Refractory Solid Tumors Phase 1
Completed NCT02247401 - Coadministration of ABT-450/Ritonavir/ABT-267 (ABT-450/r/ABT-267) With Ribavirin (RBV) in Adults With Genotype 4 (GT4) Hepatitis C Virus (HCV) in Egypt Phase 3
Completed NCT02582632 - A Study to Evaluate Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir in Treatment-Naïve Hepatitis C Virus Genotype 1b-Infected Adults Phase 3
Terminated NCT01532908 - Open Label Study of the Efficacy and Safety of MBL-HCV1 in Combination With Oral Direct-Acting Antivirals in Patients Undergoing Liver Transplantation for Hepatitis C Phase 2
Recruiting NCT01754961 - Effects of Vitamin D on Inflammation in Liver Disease Phase 2
Terminated NCT01465516 - Treating Hispanic Patients Diagnosed With Hepatitis C Using Boceprevir N/A
Completed NCT01265511 - Study of SCY-635, Pegasys and Copegus in Hepatitis C Phase 2
Completed NCT04042740 - Glecaprevir/Pibrentasvir Fixed-dose Combination Treatment for Acute Hepatitis C Virus Infection Phase 2
Not yet recruiting NCT05601518 - Efficacy and Safety of Coblopasvir Hydrochloride Capsules Combined With Sofosbuvir Tablets for the Treatment of Chronic HCV Infection: A Prospective, Multi-center Real-world Study.
Terminated NCT02429583 - Effects of Persistent Innate Immune Activation on Vaccine Efficacy Phase 4
Not yet recruiting NCT05506475 - Evaluation of HCV Care and Treatment for HIV-HCV Co-infected Patients in Decentralised Areas in Vietnam
Terminated NCT01841502 - Interaction Between Paroxetine and Telaprevir Phase 2
Withdrawn NCT02112630 - Boceprevir in End Stage Renal Disease (ESRD) N/A
Completed NCT02076100 - Safety, Pharmacokinetics, and Pharmacodynamics of Ruzasvir (MK-8408) in Participants With Hepatitis C Infection (MK-8408-003) Phase 1
Completed NCT01803308 - A Multiple Ascending Dose Phase I Study of SB 9200 in Treatment Naïve Adults With Chronic Hepatitis C Infection Phase 1
Terminated NCT01560468 - Study of Hepatitis C Virus (HCV) Entry Inhibitor in Liver Transplant Recipients With HCV Infection Phase 1