Dose-Escalation Study Evaluating the Safety and Pharmacokinetics of Artesunate in Patients With Hepatocellular Carcinoma

NCT02304289 | Terminated Phase 1

• 2 other identifiers: AGO/2014/0032014-002503-16
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the Safety and Pharmacokinetics of Oral Artesunate in patients with advanced hepatocellular carcinoma (HCC)

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (3)

• Number of Participants with Adverse Events as a Measure of Safety and Tolerability

  14 days

• Maximum tolerated dose (MTD)

  14 days

• Pharmacokinetic analysis of Cmax, Cmin, Tmax, and AUC.

  2 days

Secondary Outcomes (3)

• Time to tumor progression (TTP)

  Time from the first intake of Artesunate to radiological progression

• Overall survival (OS)

  ime from the first intake of Artesunate to death

• Quality of life based on the "Functional Assessment of Cancer Therapy Hep-30 scale" (FACT-Hep-30)

  14 days

Study Arms (1)

Oral Artesunate

EXPERIMENTAL

The first patient will receive 200 mg Artesunate once-daily for 14 days. If no dose-limiting toxicity (DLT) is observed after 14 days, the next patient will start at a daily dose of 300 mg Artesunate. If no DLT is observed after 14 days, a cohort of 3 patients will receive 400 mg once-daily for 14 days. For each subsequent cohort of 3 patients 200 mg will be added to the dose, until the maximum tolerated dose (MTD) is determined.

Drug: Artesunate

Interventions

Artesunate DRUG

Oral Artesunate once-daily for 14 days, dose-escalation

Oral Artesunate

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed advanced HCC, based on the report of the department of pathology, excluding fibrolamellar carcinoma.
• Liver mass measuring at least 2 cm with characteristic vascularization seen on either triphasic computed tomography (CT) scan or magnetic resonance imaging (MRI) with gadolinium
• Patients must have refused treatment with sorafenib or must have had treatment with sorafenib, which was either stopped due to intolerance or therapeutic failure.
• ECOG PS of 0-2.
• Child Pugh class ≤ B7
• Life expectancy greater than 3 months in the Investigator's opinion
• Adequate bone marrow function
• Adequate hepatic function
• Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin (β-hCG) or urine pregnancy test at screening. Women who are pregnant or breast feeding are ineligible for this study.
• For women who are not postmenopausal (12 months of amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to use adequate methods of contraception (e.g., hormonal implants, combined oral contraceptives, vasectomized partner), during the treatment period and for at least 3 months after the last dose of study treatment
• For men: agreement to use a barrier method of contraception during the treatment period and for at least 3 months after the last dose of the study treatment.
• Adequate renal function
• Each subject (or their legally acceptable representative) must be able and willing to provide an written informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and are willing to participate in the study.
• Able to swallow capsules
• Adequate coagulation tests: international normalized ratio (INR) ≤1.5 x ULN

You may not qualify if:

• Patients with Child-Pugh classification \> B7
• Major debilitating disease limiting survival prognosis (incl. heart failure, uncontrolled diabetes, psychiatric disease, hemodialysis, and respiratory insufficiency)
• Any mental deficiency preventing proper understanding of trial protocol requirements
• Remaining toxicities from previous sorafenib treatment will be individually evaluated and well documented by the PI.
• QTc≥440 msec
• Patients suffering from sinus bradycardia, bradyarrythmia, AV-block I or III.
• Known allergy to ART or to other artemisinin derivatives
• Malabsorption or intestinal obstruction
• History of venous thromboembolic disease within 3 months prior to first administration of study treatment
• The patient has current, severe and uncontrolled medical condition such as infection, diabetes mellitus or other systemic disease
• Any condition or illness that, in the opinion of the Investigator or the medical monitor, would compromise patient safety or interfere with the evaluation of the safety of the drug
• The patient has known positive serology for human immunodeficiency virus
• Essential medications that are known potent inhibitors or inducers of CYP2B6 and/or CYP3A4
• Fibrolamellar carcinoma

Sponsors & Collaborators

• University Hospital, Ghent: lead
• University Ghent: collaborator
• Anticancer Fund, Belgium: collaborator

Study Sites (1)

Dept. of Hepatology & Gastroenterology Ghent University Hospital

Ghent, East-Flandres, 9000, Belgium

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Artesunate

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

Intervention Hierarchy (Ancestors)

Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Sesquiterpenes; Terpenes; Hydrocarbons

Study Officials

• Hans Van Vlierberghe, MD, PhD

  University Ghent

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2014
• First Posted: December 1, 2014
• Study Start: November 1, 2014
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: October 27, 2021

Record last verified: 2017-01

Locations

BE (1)