Phase I/II Study of PTX-9908 Injection As an Inhibitor of Cancer Progression in Patients with Non-resectable Hepatocellular Carcinoma Following Transarterial Chemoembolization Treatment
This is a multicenter, Phase I/II study in patients with non-resectable hepatocellular carcinoma following TACE treatment. Phase I (Open-label dose escalation) This study will be an open-label study with an Accelerated Phase and a Standard Phase. For the Accelerated Phase of the study, one patient per dose level (1 mg/kg, and 2 mg/kg) is planned. For the dose levels in the standard phase (4 mg/kg, 8 mg/kg and 16 mg/kg), it will follow the Fibonacci's rule of 3 + 3 design. All eligible patients who have received TACE treatment and recovered well, will be administrated PTX-9908 Injection intravenously one dose per day for 5 days on Week 1 (excludes weekends and public holidays), and one dose per week (on Day 8, Day 15, and Day 22) for 3 consecutive weeks. The 4-week treatment period, will be followed by a 2-week follow-up period. Phase II (Randomized placebo controlled dose expansion) The objective of phase II is to further evaluate the safety, tolerability and antitumor activity of PTX-9908 Injection for patients with non-resectable hepatocellular carcinoma following TACE treatment. Approximately 24 eligible patients who have received TACE treatment and recovered, will be randomized to PTX-9908 Injection using the predetermined dose in phase I or the vehicle placebo in a 2:1 ratio. PTX-9908 Injection or placebo will be administered intravenously one dose per day for 5 days in Week 1 (excludes weekends and public holidays), and one dose per week till Week 12 (Day 78). The 12-week treatment period, will be followed by a 2-week follow-up period.
• Unresectable hepatocellular carcinoma and at intermediate-stage HCC (BCLC stage B or Child-Pugh class A/B with large or multifocal HCC, no vascular invasion, or extrahepatic spread) with completed TACE procedure in 4 weeks before day 1 of study intervention infusion.
• Recovered from TACE treatment and procedure related toxicities including ALT/AST and bilirubin within normal limit or reference numeric value (reference value is defined as the test value before TACE procedure).
• ECOG (Eastern Cooperative Oncology Group) performance status \< 2.
• Have adequate organ and marrow function as defined below:
∙ Absolute neutrophil count \> 1,200/µL
‣ Hemoglobin \> 9 g/dL
‣ Platelets \> 100,000/µL
‣ Total bilirubin \< 2 X ULN
• Have adequate kidney function as estimated glomerular filtration rate (eGFR) \> 60 mL/min/1.73m2
• A negative pregnancy test at screening. This applies to any female patient with childbearing potential.
• Agree to use adequate contraception after signing informed consent form, during the duration of study participation and for at least 4-weeks after completion or withdrawal from the study. This applies to any female patient with childbearing potential and any male patient whose female partner has childbearing potential.
• Acceptable contraceptive methods include:
‣ Established use of oral, injected or implanted hormonal methods of contraception
‣ Placement of an intrauterine device (IUD) or intrauterine system (IUS)
‣ Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) \>=20 years of age. (Note: In Taiwan, age of majority recognized in law is 20 years of age)
• \>=20 years of age. (Note: In Taiwan, age of majority recognized in law is 20 years of age)
• Anticipated life expectancy of \>= 6 months at assessment during screening.
⁃ Ability to understand and have signed a written informed consent document.