Status:

TERMINATED

Study of GNS561 in Patients With Liver Cancer

Lead Sponsor:

Genoscience Pharma

Conditions:

Hepatocellular Carcinoma

Cholangiocarcinoma, Intrahepatic

Eligibility:

All Genders

18+ years

Phase:

PHASE1

PHASE2

Brief 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

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 ...

Eligibility Criteria

Inclusion

  • 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
  • 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.

Exclusion

  • 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.
  • 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

Key Trial Info

Start Date :

April 4 2018

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

April 25 2022

Estimated Enrollment :

50 Patients enrolled

Trial Details

Trial ID

NCT03316222

Start Date

April 4 2018

End Date

April 25 2022

Last Update

May 2 2022

Active Locations (5)

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Page 1 of 2 (5 locations)

1

Memorial Sloan Kettering

New York, New York, United States, 10065

2

Jules Bordet Institute

Brussels, Belgium

3

CHU Grenoble

Grenoble, France, 38043

4

Croix-Rousse Hospital

Lyon, France, 69004