Clinical Trials /

A Study of PTX-9908 Injection for Non-resectable HCC With TACE

NCT03812874

Description:

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.

Related Conditions:
  • Hepatocellular Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of PTX-9908 Injection for Non-resectable HCC With TACE
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: PTX-9908-HCC-01
  • NCT ID: NCT03812874

Conditions

  • Carcinoma, Hepatocellular

Interventions

DrugSynonymsArms
PTX-9908 InjectionPTX-9908 Injection group
PlaceboPlacebo/Vehicle group

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
PTX-9908 Injection groupExperimentalIV injection.
  • PTX-9908 Injection
Placebo/Vehicle groupPlacebo ComparatorIV injection
  • Placebo

Eligibility Criteria

        Inclusion Criteria:

          1. 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.

          2. Recovered from TACE treatment and procedure related toxicities including ALT/AST and
             bilirubin within normal limit or 1.5x of reference numeric value (reference value is
             defined as the test value before TACE procedure).

          3. ECOG (Eastern Cooperative Oncology Group) performance status < 2.

          4. Have adequate organ and marrow function as defined below:

               -  Absolute neutrophil count > 1,200/µL

               -  Hemoglobin > 9g/dL

               -  Platelets > 100,000/µL

               -  Total bilirubin < 2 X ULN

               -  AST < 5 X ULNs

               -  ALT < 5 X ULNs

               -  Creatinine < 2.5 X ULN

          5. A negative pregnancy test at Screening. This applies to any female patient with
             childbearing potential.

          6. 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:

               1. Established use of oral, injected or implanted hormonal methods of contraception

               2. Placement of an intrauterine device (IUD) or intrauterine system (IUS)

               3. Barrier methods of contraception: condom or occlusive cap (diaphragm or
                  cervical/vault caps)

          7. >= 20 years of age (Note: In Taiwan, age of majority recognized in law is 20 years of
             age.)

          8. Anticipated life expectancy of >= 6months at assessment during screening.

          9. Ability to understand and have signed a written informed consent document.

        Exclusion Criteria:

          1. Patients with Child-Pugh B8-9.

          2. Patient who has had anti-cancer therapy including surgery, radiotherapy,
             immunotherapy, or chemotherapy (except in TACE regimen) within 4 weeks prior to the
             screening visit.

          3. Patient who has received any other investigational agents within 4 weeks prior to the
             screening visit.

          4. Patient who has not recovered from the side effects of the earlier investigational
             agent or had anti-cancer therapy including surgery, radiotherapy, immunotherapy, or
             chemotherapy.

          5. Patient with known brain metastases, leptomeningeal or epidural metastases (unless
             treated and well controlled for >= 3 months).

          6. Patient with prior history of co-malignancies, except for adequately treated carcinoma
             in situ of the cervix, ductal carcinoma in situ (DCIS) of the breast, and basal
             cell/squamous cell skin cancer.

          7. Patient with history of myocardial infarction or uncontrolled cardiac dysfunction, or
             unstable arrhythmia or symptomatic peripheral arterial vascular disease.

          8. Patient with history of positive serology for human immunodeficiency virus (HIV).

          9. Patient with active, uncontrolled bacterial, viral, or fungal infections, which
             require systemic therapy.

         10. Patient with poor liver function as indicated by serum bilirubin > 2 mg/dL, Child-Pugh
             Class C, severe coagulopathy (INR > 2) not correctable with vitamin K, or active
             hepatic encephalopathy.

         11. Patient with known allergic reactions to biological agent or polypeptides similar to
             PTX-9908 Injection.

         12. Woman who is pregnant or nursing.

         13. Patient with concomitant disease or condition that could interfere with the conduct of
             the study, or that would, in the opinion of the investigator, pose an unacceptable
             risk to the patient in this study.

         14. Patient with unwillingness or inability to comply with the study protocol for any
             reason.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:20 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety as measured by the number and severity of Adverse Events
Time Frame:Week 1 - Week 6 (Phase I)/Week 14 (Phase II)
Safety Issue:
Description:Any of the following, if judged to be associated with PTX-9908 Injection or the combination of TACE with PTX-9908 Injection (i.e., with possible causality) that occur within the DLT evaluation window, will be considered as a DLT. All Grade 4 (i.e., life-threatening) non-hematological and hematological toxicities (except for Grade 4 lymphopenia). Grade 3 anemia with clinically significant bleeding All grades of febrile neutropenia. All Grade 3 non-laboratory/non-hematologic treatment-emergent adverse events, with the exception for nausea, vomiting, or diarrhea that resolves within 3 days. In addition, for Grade 3 cytokine release syndrome, the symptoms have to persist for > 24 hours after PTX-9908 Injection administration despite symptomatic treatment.

Secondary Outcome Measures

Measure:Recommended Phase 2 Dose (RP2D)
Time Frame:Week 1 - Week 6 (Phase I only)
Safety Issue:
Description:The RP2D was based on the highest dose in which 0/6 or 1/6 participants experienced DLT with at least 2 out of no more than 6 participants experiencing DLT at the next higher dose level, and the assessment of any relevant chronic toxicity.
Measure:Maximum Plasma Concentration (Cmax) of single-dose and repeat-dose of PTX-9908 Injection
Time Frame:Day 1, Day 8, Day 15, and Day 22 in Phase I and Phase II
Safety Issue:
Description:Pharmacokinetics (PK) is a branch of pharmacology concerned with the rate at which drugs are absorbed, distributed, metabolized, and eliminated by the body. Cmax=maximum observed plasma concentration of PTX-9908 Injection administered with IV dose derived from plasma concentration versus time data.
Measure:Area Under the Curve, Extrapolated to Infinity (AUC[INF]) of single-dose and repeat-dose of PTX-9908 Injection
Time Frame:Day 1, Day 8, Day 15, and Day 22 in Phase I and Phase II
Safety Issue:
Description:PK is a branch of pharmacology concerned with the rate at which drugs are absorbed, distributed, metabolized, and eliminated by the body. AUC(INF)=area under the plasma concentration-time curve from time zero extrapolated to infinite time of PTX-9908 Injection administered with IV.
Measure:Terminal Half-life (T-Half) of single-dose and repeat-dose of PTX-9908 Injection
Time Frame:Day 1, Day 8, Day 15, and Day 22 in Phase I and Phase II
Safety Issue:
Description:PK is a branch of pharmacology concerned with the rate at which drugs are absorbed, distributed, metabolized, and eliminated by the body. T-Half=terminal-phase elimination half-life in plasma of PTX-9908 Injection administered with IV.
Measure:Overall Tumor Response
Time Frame:Week 1 - Week 6 (Phase I)/Week 14 (Phase II)
Safety Issue:
Description:Number of participants with a best overall tumor response of complete Response (CR), Partial Response (PR), Stable Disease (SD), and Progressive Disease (PD). Overall tumor response will be assessed using contrast-enhanced CT imaging according to mRECIST criteria following the 1.1 release of RECIST.
Measure:Response of target hepatic lesions in embolized territory
Time Frame:Week 1 - Week 6 (Phase I)/Week 14 (Phase II)
Safety Issue:
Description:Number of participants with hepatic lesion in embolized territory of complete Response (CR), Partial Response (PR), Stable Disease (SD), and Progressive Disease (PD). Tumor response will be assessed using contrast-enhanced CT imaging according to mRECIST criteria following the 1.1 release of RECIST
Measure:To evaluate overall time-to-progression
Time Frame:Week 1 - Week 6 (Phase I)/Week 14 (Phase II)
Safety Issue:
Description:Time to progression (TPP) will start from TACE administration to radiological progression. Definition of progression is based on the mRECIST criteria.
Measure:To evaluate change in AFP levels.
Time Frame:Week 1 - Week 6 (Phase I)/Week 14 (Phase II)
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:TCM Biotech International Corp.

Last Updated

January 17, 2019