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Hepatocellular CarcinomaPhase 1/2NCT03316222

Study of GNS561 in Patients With Liver Cancer

A Phase 1/2 study testing GNS561 in people with Hepatocellular Carcinoma and Cholangiocarcinoma, Intrahepatic, run by Genoscience Pharma at 5 sites in 3 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This is a first in human, open-label dose escalation study to investigate the safety, tolerability and pharmacokinetics of GNS561 in patients Primary and Secondary liver cancer Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
GNS561
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
5 sitesin 3 countries
Study dates
4 Apr 2018to 25 Apr 2022
Phase
Phase 1/2
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

  • Males or females ≥ 18 years of age
  • Histologically confirmed and documented locally advanced or metastatic HCC that is deemed not appropriate for curative therapy and Histologically confirmed and documented locally advanced or metastatic iCCA.
  • Liver tumor burden< 50% of the liver (per Investigator judgment)
  • Antiviral therapy required in hepatitis B virus patients (Hepatitis B antigen positive)
  • Willing to have liver biopsy at the beginning of cycle 2 (Day 1)
  • Presence of a measurable tumor per RECIST v1.1 criteria
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  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
  • Life expectancy ≥ 12 weeks
  • Adequate hematologic function prior to the first dose of GNS561, defined as:
  • Absolute neutrophils count ≥ 1500 cells/µL
  • Hemoglobin ≥ 10 g/dL with no transfusion within 4 weeks prior to first planned dose of GNS561
  • Platelet count > 50,000/µL with no transfusion within 2 weeks prior to first planned dose of GNS561
  • Adequate renal function prior to first dose, defined as
  • Serum creatinine < 1.5 ULN
  • Creatinine clearance ≥ 50 mL/min/m2 (by Cockroft-Gault equation of 24-hour urine) if creatinine ≥ 1.5 X ULN
  • Adequate hepatic function prior to first dose, defined as AST/ALT ≤ 5 X ULN
  • Women patients of childbearing potential must have a negative serum/urine pregnancy test at screening and baseline, and be willing to use a medically acceptable form, as judged by Investigator and Sponsor, of contraception (e.g., hormonal birth control, intrauterine device [IUD], or barrier method [male condom, female condom, diaphragm]), plus a spermicidal agent [contraceptive foam, jelly, or cream]) or abstinence or bilateral occlusion or whose partner had a vasectomy at least 2 years before screening. The patient should be advised to continue the contraception for at least 6 months following the completion of dosing. Women with cessation for > 24 months of previously occurring menses, or women of any age who have had a hysterectomy, or have had both ovaries removed will be considered to be of non-childbearing potential.
  • Male patients of reproductive potential must be willing to use one acceptable method of contraception, as judged by Investigator and Sponsor, as described in Criteria 12 and/or to refrain from donating sperm from the time of screening through at least 6 months following the completion of dose administration.
  • Amenable to computed tomography (CT) with 3 or 4 phase liver or magnetic resonance imaging (MRI) of abdomen and pelvis, and CT of chest, or MRI of whole body, for initial tumor size measurements and subsequent follow-up.
  • Absence of other clinically relevant abnormalities for screening laboratory test results as judged by the Investigator and Sponsor.
  • Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
  • Be willing to abstain from alcohol from signing of informed consent through Week 5 (completion of PK sampling at the beginning of Cycle 2).
  • Able to understand and provide written informed consent.

Who cannot join

  • Pregnant or breast-feeding mothers
  • Any known history of encephalopathy
  • Known esophageal varices with recent history of bleeding (within previous 2 months)
  • Clinically significant ascites or paracentesis
  • Known untreated or symptomatic brain metastases
  • Presence of residual toxicities of ≥ Grade 2 after prior antitumor therapy ≤ 4 weeks prior to first dose. Grade 1 toxicities related to previous treatments are acceptable at the time of the first planned dose of GNS561, as well as any alopecia.
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  • Chronic treatment with immunosuppressive agents (like steroids) ≤ 6 weeks prior to first planned dose of GNS561.
  • Major surgical procedures, open biopsy or significant traumatic injury ≤ 4 weeks prior to first dose of GNS561 or anticipation of major surgical procedure during the course of the trial, minor surgical procedures ≤ 1 week of first planned dose
  • Any clinically significant cardiovascular condition as judged by the Investigator
  • Severe or uncontrolled renal condition
  • Untreated chronic hepatitis B
  • Known history of immunodeficiency diseases (e.g., active HIV)
  • Use of any prohibited concomitant medications within 14 days of the Baseline/Day 1 visit
  • Known current alcohol (> 20g/ Day in women and > 30g/ Day in men) or substance abuse
  • Malabsorption issues (e.g., gastric bypass or gastrectomy patients)
  • Participation in any investigational clinical investigation ≤ 4 weeks prior to first planned dose of GNS561 or longer if required by local regulations, and for any other limitation of participation based on local regulations
  • Known clinically significant or life threatening organ or systemic disease such that in the opinion of the Investigator, the significance of the disease will compromise the patient's participation in the trial
  • Is a participant or plans to participate in another investigational clinical study, while taking part in this study.
  • Known intolerance or hypersensitivity to the active ingredient or to one of the components of the study drug

Trial locations and contacts

5 sites in 3 countries.

5 sites in 3 countries

France3 sites

  • CHU Grenoble

    Grenoble, 38043

  • Croix-Rousse Hospital

    Lyon, 69004

  • Saint-Joseph Hospital

    Paris, 75014

Other trials in France

United States1 site

  • Memorial Sloan Kettering

    New York, New York, 10065

Other trials in United States

Belgium1 site

  • Jules Bordet Institute

    Brussels

Other trials in Belgium

About this study

Official title: Phase 1/2a Study to Evaluate the Safety, Activity, and Pharmacokinetics of Escalating Doses of GNS561 in Patients With Primary and Secondary Liver Cancer

This is a first in human, open-label dose escalation study to investigate the safety, tolerability and pharmacokinetics of GNS561 in patients Primary and Secondary liver cancer

Read the detailed description

This is a multicenter, open-label, uncontrolled, repeat-dose Phase 1/2a study designed to evaluate the safety profile and to determine the recommended Phase 2 dose of GNS561 in patients with advanced primary and secondary liver cancer. This study will enroll approximately 50 patients and consists of 2 parts: Phase 1(dose escalation) and Phase 2 (expansion). All patients will be treated until the occurrence of an unacceptable toxicity, disease progression, or withdrawal of consent. In this study a treatment cycle is defined as 4 weeks (28 days). Patients are to take their assigned dose of GNS561, in the Morning and in the evening at the same time everyday, following a meal.

Being tested
GNS561
Medical subject headings
Carcinoma, Hepatocellular, Cholangiocarcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GNS561Drug

    Escalating doses to be administered 3 times a week.

Study groups in NCT03316222
Study groupRoleWhat they receive
Dose escalationExperimentalDose escalation using 3+3 design with dose limiting toxicity (DLT) observation period of 28 days.
Receives: Drug: GNS561
Dose ExpansionExperimentalAdditional patients will be enrolled into the recommended dose. These additional patients will undergo all of the same assessments as the patients enrolled in dose escalation with the exception of PK sampling.
Receives: Drug: GNS561

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose-Limiting Toxicity

    Dose-Limiting Toxicity will be measured by adverse events by dose level

    Measured: Dose-Limiting Toxicity will be evaluated during the 4 - week dose escalation phase.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Oct 2017
  2. Study start4 Apr 2018
  3. Primary completion15 Jan 2021
  4. Study completion25 Apr 2022

Why it stopped: only phase 1b was completed and the phase 2 will be an another study, finally

Resources

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
50 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03316222
Sponsor's protocol ID
GNS561-CL-I-Q-0211
Status last verified
Apr 2022
First submitted
10 Oct 2017
Last updated
2 May 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Harding JJ, Awada A, Roth G, Decaens T, Merle P, Kotecki N, Dreyer C, Ansaldi C, Rachid M, Mezouar S, Menut A, Bestion EN, Paradis V, Halfon P, Abou-Alfa GK, Raymond E. First-In-Human Effects of PPT1 Inhibition Using the Oral Treatment with GNS561/Ezurpimtrostat in Patients with Primary and Secondary Liver Cancers. Liver Cancer. 2022 Feb 15;11(3):268-277. doi: 10.1159/000522418. eCollection 2022 Jun.

    PubMed 35949290

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing GNS561 in people with Hepatocellular Carcinoma and Cholangiocarcinoma, Intrahepatic, run by Genoscience Pharma at 5 sites in 3 countries.

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 23 inclusion and 19 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 2 May 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in France, United States, 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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: only phase 1b was completed and the phase 2 will be an another study, finally). 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?

Dose-Limiting Toxicity (time frame: Dose-Limiting Toxicity will be evaluated during the 4 - week dose escalation phase.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03316222, which also lists 1 linked publication.

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 2 May 2022.

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