Hepatocellular carcinoma Intrahepatic cholangiocarcinoma Pancreatic adenocarcinoma with liver metastasis Colorectal cancer with liver metastasis MedDRA version: 20.0 Level: LLT Classification code 10019828 Term: Hepatocellular carcinoma non-resectable System Organ Class: 100000004864 MedDRA version: 20.0 Level: LLT Classification code 10077738 Term: Hepatocellular carcinoma metastatic System Organ Class: 100000004864 MedDRA version: 20.0 Level: LLT Classification code 10073077 Term: Intrahepa
Conditions
Interventions
Product Code: GNS561
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: not available
CAS Number: 1914148-72-3
Current Sponsor code: GNS561
Concentration unit: mg milligram(s)
Concentration type:
Sponsors
GENOSCIENCE PHARMA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Males or females = 18 years of age. 2. Histologically confirmed and documented locally advanced or metastatic hepatocarcinoma (HCC) that is deemed not appropriate for curative therapy or histologically confirmed and documented locally advanced or metastatic intrahepatic carcinoma (iCCA) or or histologically confirmed and documented pancreatic ductal adenocarcinoma (PDAC) with liver metastasis or histologically confirmed and documented colorectal cancer (CRC) with liver metastasis. 3. Liver tumor burden 50,000/µL with no transfusion within 2 weeks prior to first planned dose of GNS561 13. Adequate renal function prior to first dose, defined as a. Serum creatinine 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 pote
Exclusion criteria
Exclusion criteria: 1. Pregnant or breast-feeding mothers 2. Prior history of acrodermatitis enteropathica or known ZIP4 genetic mutations 3. Any known history of encephalopathy 4. Known esophageal varices with recent history of bleeding (within previous 2 months) 5. Clinically significant ascites or paracentesis 6. Concurrent hematologic malignancies or other malignancy, with the exception of: a) Curatively resected non-melanoma skin cancer; b) Curatively treated cervical carcinoma in situ. 7. Known untreated or symptomatic brain metastases 8. Prior antitumor treatment, including chemotherapy, biologic, experimental, hormonal or radiotherapy within 4 weeks of first dose of GNS561with the following exceptions: a. Maintenance hormonal therapy for metastatic prostate and breast cancer b. Hormone-replacement therapy or oral contraceptives c. Palliative radiation to bone metastases within 2 weeks prior to first dose 9. Previous treatment with ZIP4 targeted therapy 10. Known allergic reaction to quinoline derivatives (e.g., quinine, chloroquine, Mefloquine) 11. 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. 12. Chronic treatment with immunosuppressive agents(like steroids) = 6 weeks prior to first planned dose of GNS561. 13. 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 14. Any clinically significant cardiovascular condition as judged by the Investigator 15. Severe or uncontrolled renal condition 16. Untreated chronic hepatitis B 17. Known history of immunodeficiency diseases (e.g., active HIV) 18. Use of any prohibited concomitant medications within 14 days of the Baseline/Day 1 visit 19. Known current alcohol (> 20g/ Day in women and >30g/ Day in men) or substance abuse 20. Malabsorption issues (e.g., gastric bypass or gastrectomy patients) 21. Patient with a mental or legal disability 22. 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 23. 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 24. Is a participant or plans to participate in another investigational clinical study, while taking part in this study. 25. Known intolerance or hypersensitivity to the active ingredient or to one of the components of the study drug
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase 1: • To characterize the safety and tolerability of GNS561 • To identify the recommended Phase 2 dose (RD) • To characterize the PK of GNS561 Phase 2a: • To characterize the safety and tolerability of GNS561 • To identify evidence of antitumor activity (tumor control rate : overall response rate + SD by RECIST 1.1) ;Secondary Objective: Exploratory objectives: • Pharmacodynamics (PD) biomarker expression in blood including a-fetoprotein (AFP), CA-19-9 and CEA. • PD biomarker expressions in liver biopsies ZIP4, Ki67 expression by immunostaining and an autophagy marker (LC3-II). • To assess the liver/plasma ratio of GNS561 after repeated dosing • To assess the anti-fibrotic effect of GNS561 in liver after repeated dosing (for Phase 2a only) by a FibroScan® and calculation of a fibrosis score (FibroTest®/FibroSURE™) ;Primary end point(s): Safety: • Incidence and nature of DLTs by dose level during the 4 week dose escalation phase • Incidence, nature, and severity of adverse events • Change in vital signs, clinical laboratory (chemistry and hematology) values, urinalysis, electrocardiogram (ECGs) Efficacy: • Response rate (CR+ PR) • Disease control rate (CR+PR+SD) • Progression free survival Pharmacokinetics: • GNS561 PK over first 48 hours following first and repeated dose in Cycle 1 and Cycle 2;Timepoint(s) of evaluation of this end point: Safety evaluation: at each visit Efficacy evaluation: on week 9 and all 8 weeks (tumor RECIST) PK evaluation: D1, D2, D3 of Cycle 1 and Cycle 2. Weekly during Cycle 1 and D1 of Cycle 3, Cycle 4 and Cycle 5. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Exploratory endpoints: • PD biomarker expressions in blood including AFP for HCC patients, CEA and CA-19-9 for iCCA, PDAC and CRC patients. • PD biomarker expressions in liver biopsies including ZIP4 and Ki67 expression by immunostaining and an autophagy marker (LC3-II). • Liver/plasma ratio of GNS561 after repeated dosing at the beginning of Cycle 2 • Assessment of the anti-fibrotic effect of GNS561 in liver after repeated dosing (for Phase 2a only) by a FibroScan® and calculation of a fibrosis score (FibroTest®/FibroSURE™) for patients with primary liver cancer.;Timepoint(s) of evaluation of this end point: AFP, CA-19-9 and CEA : at screening, then beginning of each cycle from C2 and final follow-up visit. FibroScan and fibrosis score: at baseline and every 6 months. | — |
Countries
Belgium, United States
Contacts
Public ContactClinical Trials Information
GENOSCIENCE PHARMA
Outcome results
None listed