Phase 1/2a Study to Evaluate the Safety, Activity, and Pharmacokinetics of Escalating Doses of GNS561 in Patients With Primary and Secondary Liver Cancer
Overview
- Phase
- Phase 1
- Intervention
- GNS561
- Conditions
- Hepatocellular Carcinoma
- Sponsor
- Genoscience Pharma
- Enrollment
- 50
- Locations
- 5
- Primary Endpoint
- Dose-Limiting Toxicity
- Status
- Terminated
- Last Updated
- 4 years ago
Overview
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 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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 GNS
- •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
Arms & Interventions
Dose escalation
Dose escalation using 3+3 design with dose limiting toxicity (DLT) observation period of 28 days.
Intervention: GNS561
Dose Expansion
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.
Intervention: GNS561
Outcomes
Primary Outcomes
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