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Study of GNS561 in Patients With Liver Cancer

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ClinicalTrials.gov Identifier: NCT03316222
Recruitment Status : Recruiting
First Posted : October 20, 2017
Last Update Posted : May 7, 2018
Sponsor:
Information provided by (Responsible Party):
Genoscience Pharma

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma Cholangiocarcinoma, Intrahepatic Drug: GNS561 Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : April 4, 2018
Estimated Primary Completion Date : January 15, 2020
Estimated Study Completion Date : January 15, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Dose escalation
Dose escalation using 3+3 design with dose limiting toxicity (DLT) observation period of 28 days.
Drug: GNS561
Escalating doses to be administered 3 times a week.

Experimental: Dose Continuation
Additional 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.
Drug: GNS561
Escalating doses to be administered 3 times a week.




Primary Outcome Measures :
  1. Dose-Limiting Toxicity [ Time Frame: Dose-Limiting Toxicity will be evaluated during the 4 - week dose escalation phase. ]
    Dose-Limiting Toxicity will be measured by adverse events by dose level



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03316222


Contacts
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Contact: Christelle Ansaldi, MD (+33)04 91 26 99 58 cansaldi@genosciencepharma.com

Locations
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United States, New York
Memorial Sloan Kettering Not yet recruiting
New York, New York, United States, 10065
Contact: Jim Harding, PhD         
Principal Investigator: Jim Harding, PhD         
Belgium
Jules Bordet Institute Recruiting
Brussel, Belgium
Contact: Ahmad Awada, PhD         
Principal Investigator: Ahmad Awada, PhD         
France
Croix-Rousse Hospital Not yet recruiting
Lyon, France, 69004
Contact: Philippe Merle, PhD         
Principal Investigator: Philippe Merle, PhD         
Saint-Joseph Hospital Not yet recruiting
Paris, France, 75014
Contact: Chantal Drey, MD         
Principal Investigator: Chantal Drey, MD         
Sponsors and Collaborators
Genoscience Pharma

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Responsible Party: Genoscience Pharma
ClinicalTrials.gov Identifier: NCT03316222     History of Changes
Other Study ID Numbers: GNS561-CL-I-Q-0211
First Posted: October 20, 2017    Key Record Dates
Last Update Posted: May 7, 2018
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Hepatocellular
Cholangiocarcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases