Clinical Trials /

Study of GNS561 in Patients With Liver Cancer

NCT03316222

Description:

This is a first in human, open-label dose escalation study to investigate the safety, tolerability and pharmacokinetics of GNS561 in patients with advanced malignancies including hepatocellular carcinoma.

Related Conditions:
  • Hepatocellular Carcinoma
Recruiting Status:

Unknown status

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of GNS561 in Patients With Liver Cancer
  • Official Title: Phase 1/2a Study to Evaluate the Safety, Activity, and Pharmacokinetics of Escalating Doses of GNS561 in Patients With Advanced Malignancies Including Hepatocellular Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: GNS561-CL-I-Q-0211
  • NCT ID: NCT03316222

Conditions

  • Hepatocellular Carcinoma
  • Cholangiocarcinoma, Intrahepatic

Interventions

DrugSynonymsArms
GNS561Dose escalation

Purpose

This is a first in human, open-label dose escalation study to investigate the safety, tolerability and pharmacokinetics of GNS561 in patients with advanced malignancies including hepatocellular carcinoma.

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 malignancies such as HCC. This study will enroll approximately 50
      patients and consists of 2 parts: Phase 1(dose escalation) and Phase 2 (continuation). 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, at the same time each Monday,
      Wednesday and Friday following a meal.
    

Trial Arms

NameTypeDescriptionInterventions
Dose escalationExperimentalDose escalation using 3+3 design with dose limiting toxicity (DLT) observation period of 28 days.
  • GNS561
Dose ContinuationExperimentalAdditional 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.
  • GNS561

Eligibility Criteria

        Inclusion Criteria:

          1. Males or females ≥ 18 years of age

          2. Histologically confirmed and documented locally advanced or metastatic HCC that is
             deemed not appropriate for curative therapy.

          3. Liver tumor burden< 50% of the liver (per Investigator judgment)

          4. Antiviral therapy required in hepatitis B virus patients (Hepatitis B antigen
             positive)

          5. Willing to have liver biopsy at the beginning of cycle 2 (Day 1)

          6. Presence of a measurable tumor per RECIST v1.1 criteria

          7. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1

          8. Life expectancy ≥ 12 weeks

          9. Adequate hematologic function prior to the first dose of GNS561, defined as:

               1. Absolute neutrophils count ≥ 1500 cells/µL

               2. Hemoglobin ≥ 10 g/dL with no transfusion within 4 weeks prior to first planned
                  dose of GNS561

               3. Platelet count > 50,000/µL with no transfusion within 2 weeks prior to first
                  planned dose of GNS561

         10. Adequate renal function prior to first dose, defined as

               1. Serum creatinine < 1.5 ULN

               2. Creatinine clearance ≥ 50 mL/min/m2 (by Cockroft-Gault equation of 24-hour urine)
                  if creatinine ≥ 1.5 X ULN

         11. Adequate hepatic function prior to first dose, defined as AST/ALT ≤ 5 X ULN

         12. 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 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.

         13. 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
             and/or to refrain from donating sperm from the time of screening through at least 6
             months following the completion of dose administration.

         14. 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.

         15. Absence of other clinically relevant abnormalities for screening laboratory test
             results as judged by the Investigator and Sponsor.

         16. Willingness and ability to comply with scheduled visits, treatment plan, laboratory
             tests, and other study procedures.

         17. Be willing to abstain from alcohol from signing of informed consent through Week 5
             (completion of PK sampling at the beginning of Cycle 2).

         18. Able to read, understand and provide written informed consent.

        Exclusion Criteria:

          1. Pregnant or breast-feeding mothers

          2. Any known history of encephalopathy

          3. Known esophageal varices with recent history of bleeding (within previous 2 months)

          4. Clinically significant ascites or paracentesis

          5. Known untreated or symptomatic brain metastases

          6. 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.

          7. Chronic treatment with immunosuppressive agents (like steroids) ≤ 6 weeks prior to
             first planned dose of GNS561.

          8. 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

          9. Any clinically significant cardiovascular condition as judged by the Investigator

         10. Severe or uncontrolled renal condition

         11. Untreated chronic hepatitis B

         12. Known history of immunodeficiency diseases (e.g., active HIV)

         13. Use of any prohibited concomitant medications within 14 days of the Baseline/Day 1
             visit

         14. Known current alcohol (> 20g/ Day in women and > 30g/ Day in men) or substance abuse

         15. Malabsorption issues (e.g., gastric bypass or gastrectomy patients)

         16. 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

         17. 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

         18. Is a participant or plans to participate in another investigational clinical study,
             while taking part in this study.

         19. Known intolerance or hypersensitivity to the active ingredient or to one of the
             components of the study drug
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose-Limiting Toxicity
Time Frame:Dose-Limiting Toxicity will be evaluated during the 4 - week dose escalation phase.
Safety Issue:
Description:Dose-Limiting Toxicity will be measured by adverse events by dose level

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Genoscience Pharma

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