Quizartinib for Liver Disease
Recruiting in Palo Alto (17 mi)
+2 other locations
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Daiichi Sankyo
No Placebo Group
Approved in 2 jurisdictions
Trial Summary
What is the purpose of this trial?This study will evaluate and compare the PK in subjects with severe HI to that of matched healthy control subjects with normal hepatic function.
Is the drug Quizartinib a promising treatment for liver disease?The provided research articles do not mention Quizartinib or its effectiveness for liver disease. They focus on other drugs for treating hepatitis C, a liver disease, but do not provide information about Quizartinib.57121314
What safety data is available for Quizartinib (Vanflyta) in liver disease treatment?The provided research does not contain safety data for Quizartinib (Vanflyta) in the treatment of liver disease. The studies focus on other treatments like regorafenib, masitinib, and cabozantinib for hepatocellular carcinoma, but none mention Quizartinib or Vanflyta.23489
What data supports the idea that Quizartinib for Liver Disease is an effective treatment?The available research does not provide any data on Quizartinib for Liver Disease. Instead, it discusses other drugs like Regorafenib and Donafenib for liver cancer, showing they can improve survival in patients with advanced liver cancer. There is no information on Quizartinib's effectiveness for liver disease in the provided research.1261011
Do I have to stop taking my current medications for this trial?The trial protocol does not specify if you need to stop taking your current medications. However, it excludes participants with certain medical conditions and those with a history of severe adverse reactions to drugs, which might imply some restrictions. Please consult with the trial coordinators for specific guidance.
Eligibility Criteria
This trial is for men and women aged 18-75 with severe liver impairment, a BMI of 18-37, and at least 40 kg in weight. Women must not undergo egg retrieval or donate eggs during the study and for seven months after. Men must use contraception or be surgically sterilized. Participants cannot have certain liver diseases, serious medical conditions that could affect the study's safety or results, recent significant illness, known allergies to Quizartinib ingredients, or a history of digestive surgery affecting drug absorption.Inclusion Criteria
I am between 18 and 75 years old, with a BMI of 18 to 37, and weigh at least 40 kg.
I am a male and have been sterilized, practice abstinence, or agree to use contraception during and up to 4 months after treatment.
Exclusion Criteria
I have been diagnosed with primary biliary cirrhosis or primary sclerosing cholangitis.
I have been diagnosed with Gilbert's syndrome.
Participant Groups
The trial is testing Quizartinib pharmacokinetics (how the drug moves through the body) in subjects with severe hepatic impairment compared to healthy individuals. It aims to understand how liver disease affects the processing of this medication.
2Treatment groups
Experimental Treatment
Group I: Severe HIExperimental Treatment1 Intervention
Participants will receive a single oral dose of 30 mg quizartinib
Group II: Control GroupExperimental Treatment1 Intervention
Healthy participants will receive a single oral dose of 30 mg quizartinib
Quizartinib is already approved in United States, Japan for the following indications:
🇺🇸 Approved in United States as Vanflyta for:
- Acute myeloid leukemia (AML)
🇯🇵 Approved in Japan as Vanflyta for:
- Acute myeloid leukemia (AML)
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Advanced PharmaMiami, FL
Clinical Pharmacology of Miami, LLCMiami, FL
GCP ResearchSaint Petersburg, FL
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Who is running the clinical trial?
Daiichi SankyoLead Sponsor
References
Clinical and pharmacologic study of the farnesyltransferase inhibitor tipifarnib in cancer patients with normal or mildly or moderately impaired hepatic function. [2016]This study explored the feasibility of treating patients with impaired hepatic function with tipifarnib. The safety profile, pharmacokinetics, and relationship between the pharmacokinetics and toxicities were evaluated.
Regorafenib as second-line therapy for intermediate or advanced hepatocellular carcinoma: multicentre, open-label, phase II safety study. [2022]We assessed the safety of the multikinase inhibitor regorafenib in patients with hepatocellular carcinoma (HCC) that had progressed following first-line sorafenib.
Autoimmune-like hepatitis during masitinib therapy in an amyotrophic lateral sclerosis patient. [2021]We report a case of acute severe hepatitis resulting from masitinib in a young amyotrophic lateral sclerosis patient. Hepatotoxicity induced by masitinib, a tyrosine kinase inhibitor, is usually transient with mild elevation of transaminases, although acute hepatitis has been not reported to date. The hepatitis was resolved after masitinib was discontinued and a combination of prednisone and azathioprine was started. The transaminases returned to baseline normal values five months later. This is the first case in the hepatitis literature associated with masitinib. The autoimmune role of this drug-induced liver injury is discussed. Physicians should be aware of this potential complication.
Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. [2022]There are no systemic treatments for patients with hepatocellular carcinoma (HCC) whose disease progresses during sorafenib treatment. We aimed to assess the efficacy and safety of regorafenib in patients with HCC who have progressed during sorafenib treatment.
Sofosbuvir, velpatasvir and voxilaprevir combination for the treatment of hepatitis C. [2021]The advent of direct-acting antiviral (DAA) treatments for chronic hepatitis C virus (HCV) infection has dramatically increased rates of cure. However, there remain difficult-to-treat populations, including patients with genotype 3 infection and cirrhosis, and limited salvage treatment options for those that have failed first-line DAA therapy. Areas covered: This is a review of the preclinical and clinical development of sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX), an interferon-free, oral, once daily, pangenotypic treatment for chronic HCV infection. All relevant literature from 2015 through June of 2017 is included. Expert commentary: Voxilaprevir, a second-generation HCV protease inhibitor, in combination with the already approved combination of sofosbuvir and velpatasvir, was evaluated in the POLARIS trials and found to be a safe and effective regimen. Patients with prior DAA treatment failure, genotype 3, cirrhosis and/or unfavorable resistance profiles all achieved cure rates of 96% or greater. The most distinctive role for this potent regimen may prove to be as a salvage regimen for patients who have failed previous DAA therapy.
Regorafenib as treatment for patients with advanced hepatocellular cancer. [2018]Hepatocellular carcinoma is one of the fastest growing causes of cancer-related mortality worldwide. Sorafenib was the first and only drug to improve survival for patients with advanced disease, and has been the cornerstone of treatment for nearly a decade. Regorafenib is a multikinase inhibitor that has recently been shown to significantly improve survival in patients who have progressed on first-line sorafenib. In this review, we discuss the pharmacokinetic and pharmacodynamics properties of regorafenib and its efficacy and tolerability in patients with advanced hepatocellular carcinoma.
Sofosbuvir/Velpatasvir/Voxilaprevir: A Pan-Genotypic Direct-Acting Antiviral Combination for Hepatitis C. [2021]To review the efficacy and safety of sofosbuvir/velpatasvir/voxilaprevir in the treatment of hepatitis C virus (HCV) infection.
Incidence and risk of regorafenib-induced hepatotoxicity. [2019]Regorafenib, an oral multi-kinase inhibitor, has been approved for the treatments of several malignancies. Unlike traditional cytotoxic chemotherapeutic agents, regorafenib therapy often induces a distinct profile of adverse events (AEs) including hepatotoxicity. Here we conducted an up-to-date meta-analysis to assess the incidence and risk of regorafenib related hepatic toxicities. PubMed and Embase database were reviewed from inception to June 2017 for relevant trials. Eligible studies include subjects with solid tumors treated with 160 mg of regorafenib daily during the first three week of each four-week cycle, and adequate safety data reporting the elevation of aspartate transaminase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and bilirubin. Statistical analyses were conducted to calculate the summary incidence and relative risk (RR). A total of 2,213 subjects from 14 trials were included. The incidences of regorafenib-associated all-grade and high-grade hepatotoxicity were: bilirubin elevation: 23% and 5%; AST elevation: 32% and 6%; ALT elevation: 27% and 5%; ALP elevation: 31% and 2%. Regorafenib-treated subjects had a significant increased risk of all-grade (RR = 3.10; 95% CI, 2.22-4.34) and high-grade (RR = 1.74; 95% CI, 1.09-2.80) bilirubin elevation; all-grade (RR = 1.51; 95% CI, 1.13-2.00) and high-grade (RR = 1.79; 95% CI, 1.00-3.22) AST elevation; all-grade (RR = 1.82; 95% CI, 1.25-2.64) and high-grade (RR = 3.07; 95% CI, 1.30-7.22) ALT elevation; and all-grade (RR = 2.11; 95% CI, 1.01-4.40) ALP elevation. Our results suggest that regorafenib is associated with an increased risk of hepatic toxicities. Hepatotoxicity examination at regular intervals should be advised to clinicians.
Cabozantinib for the Treatment of Advanced Hepatocellular Carcinoma: Current Data and Future Perspectives. [2021]Cabozantinib (Cabometyx®) is a potent multikinase inhibitor targeting the vascular endothelial growth factor (VEGF) receptor 2, the mesenchymal-epithelial transition factor (MET) receptor, and the "anexelekto" (AXL) receptor tyrosine kinase. It is approved for the treatment of advanced hepatocellular carcinoma (HCC) after failure of sorafenib in Europe (since November 2018) and in the USA (since January 2019). The approval of cabozantinib was based on results of the randomized, placebo-controlled, phase 3 CELESTIAL trial in patients with unresectable HCC, who received one or two prior lines of treatment including sorafenib. At the second planned interim analysis, the trial was stopped, because the primary end point overall survival was clearly in favor for cabozantinib. Additionally, median progression-free survival was superior to placebo. The most common ≥ grade 3 relevant adverse events in patients with HCC treated with cabozantinib were palmar-plantar erythrodysesthesia, hypertension, fatigue, and diarrhea. In this review, current data on cabozantinib for the treatment of patients with advanced HCC, with a focus on the management of common adverse events and ongoing clinical trials, are discussed.
Regorafenib enhances antitumor immunity via inhibition of p38 kinase/Creb1/Klf4 axis in tumor-associated macrophages. [2021]Regorafenib and other multikinase inhibitors may enhance antitumor efficacy of anti-program cell death-1 (anti-PD1) therapy in hepatocellular carcinoma (HCC). Its immunomodulatory effects, besides anti-angiogenesis, were not clearly defined.
Donafenib treatment for hepatocellular carcinoma: A case report. [2023]Hepatocellular carcinoma (HCC) is the most common liver cancer. The efficacy of the present treatment is disappointing, and the prognosis is poor. Donafenib, a novel multikinase inhibitor, is a new deuterated derivative of sorafenib. It can improve overall survival in patients with advanced HCC, with a favorable safety and tolerability profile over sorafenib.
Treatment of Hepatitis C in a Case of Pediatric B-Cell Acute Leukemia. [2022]The prevalence of hepatitis C virus (HCV) infection in Pediatric patients with lymphoproliferative diseases has most commonly been reported with B cell Non-Hodgkin lymphoma. Case studies have reported the requirement of dose reduction or suspension of chemotherapy in 80% of Pediatric ALL cases who are anti-HCV positive owing to hepatotoxicity. The standard of care anti HCV therapy in children aged 3-17 years had been peginterferon and ribavirin for 48 weeks. FDA approved pan-genotypic, anti- HCV regimen, sofosbuvir/velpatasvir [SOF/VEL], for the Pediatric population >6yrs of age or >17 kg body weight in March 2020. We herein report a case of an HCV infected Pediatric B cell ALL patient who was treated with SOF/VEL concomitantly with an intensive chemotherapy regimen. Child tolerated the full dose chemotherapy along with antivirals for 12 weeks and was in morphological remission with sustained virological response.
The impact of sofosbuvir/velpatasvir/voxilaprevir treatment on serum hyperglycemia in hepatitis C virus infections: a systematic review and meta-analysis. [2023]The combination of Sofosbuvir (SOF), velpatasvir (VEL), and voxilaprevir (VOX) is an effective, safe rescue therapy for patients with previous treatment failure. Direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) infection in diabetics with a history of hypoglycemia could improve insulin resistance due to HCV clearance. However, some studies have shown that SOF/VEL/VOX causes grade 3 hyperglycemia and other adverse events, which contradicts the findings of other DAA studies.
Treatment Outcomes of Sofosbuvir/Velpatasvir/Voxilaprevir in Direct-Acting Antiviral-Experienced Hepatitis C Virus Patients: A Systematic Review and Meta-Analysis. [2023]About 5% of chronic hepatitis C (CHC) patients experienced treatment failure with direct-acting antiviral (DAA) treatment. The global data on the practice and treatment outcomes of Sofosbuvir/Velpatasvir/Voxilaprevir (SOF/VEL/VOX) in DAA-experienced CHC patients remains sparse. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of SOF/VEL/VOX as a salvage treatment in DAA-experienced CHC patients. We searched five electronic databases from inception to 31 January 2023. The study outcomes were SVR12 and treatment-related adverse effects, with subgroup analysis performed based on genotype, cirrhosis, HCC, prior SOF/VEL exposure, and region. We identified and analyzed data from 24 studies (2877 DAA-experienced CHC patients); 17.2% had prior SOF/VEL exposure, 25% received ribavirin with SOF/VEL/VOX, and 42% had pre-treatment resistance-associated substitution (RAS) testing performed. Eastern Mediterranean had a higher pooled SVR12 than the America and Europe regions (p < 0.05). Predictors of SOF/VEL/VOX failure were genotype 3, active HCC, baseline cirrhosis, and prior SOF/VEL. Baseline RAS mutation and ribavirin supplementation were not associated with higher SVR12. Treatment discontinuation because of drug-related adverse events was uncommon (10 studies, 0.2%). In summary, SOF/VEL/VOX is efficacious and safe for retreatment in DAA-experienced CHC patients, even with RAS mutation. Our findings support SOF/VEL/VOX as a first-line rescue treatment for DAA-experienced CHC patients.