Hepatocellular CarcinomaPhase 1DESPARTHNCT02304289
Dose-Escalation Study Evaluating the Safety and Pharmacokinetics of Artesunate in Patients With Hepatocellular Carcinoma
A Phase 1 study testing Artesunate in people with Hepatocellular Carcinoma, run by University Hospital, Ghent at 1 site in Belgium.
Trial summary
The purpose of this study is to evaluate the Safety and Pharmacokinetics of Oral Artesunate in patients with advanced hepatocellular carcinoma (HCC) Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- Artesunate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteBelgium
- Study dates
- Nov 2014to Dec 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
- Recovery to Grade 1 from the effects (excluding alopecia) of any prior therapy for their malignancies
- At least 4 weeks since any major surgery or open biopsy and 7 days since a core biopsy before first study treatment
- The following time must have elapsed between previous therapy for cancer and first administration of ART:
- At least 2 weeks since previous systemic targeted therapy with small molecule inhibitors, which includes any tyrosine-kinase inhibitor
- At least 4 weeks since the last dose of systemic anti-cancer therapy other than targeted therapy, which includes cytotoxic agents, monoclonal antibody therapy, immunotherapy and prior radiotherapy
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country.
Belgium1 site
Dept. of Hepatology & Gastroenterology Ghent University Hospital
Ghent, East-Flandres, 9000
About this study
Official title: Phase I Dose-Escalation Study Evaluating the Safety and Pharmacokinetics of Oral Artesunate (ART) in Patients With Advanced Hepatocellular Carcinoma (HCC).
The purpose of this study is to evaluate the Safety and Pharmacokinetics of Oral Artesunate in patients with advanced hepatocellular carcinoma (HCC)
Read the detailed description
Artemisinins, compounds extracted from the herb Artemisia annua, are safe and effective FDA-approved antimalarial drugs. Recent studies have suggested that artemisinins also exert anti-angiogenic and cytotoxic effects on human cancer cells. Artesunate (ART) is a water soluble semisynthetic artemisinin with improved pharmacokinetic properties.
A single-center phase I dose-escalation study evaluating the safety and pharmacokinetics of oral Artesunate in patients with Advanced HCC.
Approximately 15 patients will be enrolled in this trial. Dose-escalation protocol: 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.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- Artesunate
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ArtesunateDrug
Oral Artesunate once-daily for 14 days, dose-escalation
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Artesunate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Measured: 14 days
Maximum tolerated dose (MTD)
Measured: 14 days
Pharmacokinetic analysis of Cmax, Cmin, Tmax, and AUC.
Measured: 2 days
Secondary outcomes (3)
Time to tumor progression (TTP)
Measured: Time from the first intake of Artesunate to radiological progression
Overall survival (OS)
Measured: 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)
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Dec 2014 (estimated)
- Study startNov 2014
- Primary completionDec 2016
- Study completionDec 2016
Why it stopped: slow recruitment of patients
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by University Hospital, GhentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Ghent
- Sponsor type
- University, hospital or other
- Collaborators
- University Ghent, Anticancer Fund, Belgium
- Responsible party
- Sponsor
- Investigators
- Hans Van Vlierberghe, MD, PhD, Principal investigator, University Ghent
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02304289
- Sponsor's protocol ID
- AGO/2014/003
- Other IDs
- 2014-002503-16, 2014
- Acronym
- DESPARTH
- Status last verified
- Jan 2017
- First submitted
- 20 Nov 2014
- Last updated
- 27 Oct 2021
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Dose-Escalation Study Evaluating the Safety and Pharmacokinetics of Oral Artesunate (ART) in Patients With Advanced Hepatocellular Carcinoma (HCC).
- ClinicalTrials.gov ID
- NCT02304289
- Acronym / sponsor ID
- DESPARTH / AGO/2014/003
- Conditions
- Hepatocellular Carcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: slow recruitment of patients
- Enrolment
- 2 participants (actual)
- Lead sponsor
- University Hospital, GhentUniversity, hospital or other
- Collaborators
- University Ghent, Anticancer Fund, Belgium
- Study start
- Nov 2014
- Primary completion
- Dec 2016 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 1 Dec 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the Safety and Pharmacokinetics of Oral Artesunate in patients with advanced hepatocellular carcinoma (HCC)
Detailed description
Artemisinins, compounds extracted from the herb Artemisia annua, are safe and effective FDA-approved antimalarial drugs. Recent studies have suggested that artemisinins also exert anti-angiogenic and cytotoxic effects on human cancer cells. Artesunate (ART) is a water soluble semisynthetic artemisinin with improved pharmacokinetic properties.
A single-center phase I dose-escalation study evaluating the safety and pharmacokinetics of oral Artesunate in patients with Advanced HCC.
Approximately 15 patients will be enrolled in this trial. Dose-escalation protocol: 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Oral Artesunate | Experimental | Drug: ArtesunateThe 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ArtesunateOral Artesunate once-daily for 14 days, dose-escalation | Drug | Oral Artesunate |
Primary outcome
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Time frame: 14 days
Maximum tolerated dose (MTD)
Time frame: 14 days
Pharmacokinetic analysis of Cmax, Cmin, Tmax, and AUC.
Time frame: 2 days
3 secondary outcomes
Time to tumor progression (TTP)
Time frame: Time from the first intake of Artesunate to radiological progression
Overall survival (OS)
Time frame: 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)
Time frame: 14 days
Results and safety
The study was stopped early (reason given: slow recruitment of patients). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hans Van Vlierberghe, MD, PhD principal investigator
University Ghent
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Artesunate in people with Hepatocellular Carcinoma, run by University Hospital, Ghent at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 27 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: slow recruitment of patients). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants with Adverse Events as a Measure of Safety and Tolerability (time frame: 14 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2021.