Advanced hepatocellular carcinoma (HCC)in the third line or later setting MedDRA version: 21.1 Level: LLT Classification code 10049010 Term: Carcinoma hepatocellular System Organ Class: 100000004864
Conditions
Interventions
Product Name: ADI-PEG 20
Product Code: [ADI-PEG 20]
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Pegargiminase
CAS Number: 1394129-74-8
Current Sponsor code: ADI-PEG 20
Concentrati
Sponsors
POLARIS GROUP
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Advanced histologically or cytologically proven HCC (except with prior liver transplantation). 2. Treatment with at least 2 prior systemic therapy regimens. 3. Child-Pugh grade A. Child-Pugh status should be determined based on clinical findings and laboratory data during the screening period (Appendix C). 4. Measurable disease using RECIST 1.1 criteria (Appendix A). At least 1 measurable lesion must be present. Subjects who have received local-regional therapies are eligible, provided that they have either a target lesion which has not been treated with local therapy and/or the target lesion(s) within the field of the local regional therapy has shown an increase of = 20% in size. Local-regional therapy must be completed at least 4 weeks prior to the baseline CT scan. 5. ECOG performance status of 0 - 1. 6. Expected survival of at least 3 months. 7. Age = 18 years. 8. Fully recovered from any prior surgery and no major surgery within 4 weeks of initiating treatment. Surgery or procedure for placement of vascular access devices is exempt from this period. 9. Subjects must agree to use two forms of contraception or agree to refrain from intercourse for the duration of the study. For females subjects, a serum human chorionic gonadotropin (HCG) pregnancy test must be negative before entry into the study. If HCG pregnancy test is positive, further evaluation to rule out pregnancy must be performed according to GCP before this patient is claimed eligible. 10. Informed consent must be obtained prior to study initiation. 11. No concurrent investigational studies are allowed. 12. Total bilirubin 1500/µL. 15. Platelets > 75,000/µL. 16. Serum uric acid = 8 mg/dL (with or without medication control). 17. Serum creatinine = 1.5 x the upper limit of normal range, or, if serum creatinine >1.5 x the upper limit of normal range, then the creatinine clearance must be = 60 mL/min/1.73 m2 (calculated using the Jelliffe equation: calculated creatinine clearance = 98 - 0.8 [age (yrs.) - 20] /serum creatinine (x 0.9 if female). 18. Brain metastases are allowed if well controlled and without seizures. 19. Serum albumin level = 2.8 g/dL. 20. Prothrombin time (PT)-international normalized ratio (INR): PT =65 years) yes F.1.3.1 Number of subjects for this age range 91
Exclusion criteria
Exclusion criteria: 1. Serious infection requiring treatment with systemically administered antibiotics at the time of study entrance, or an infection requiring systemic antibiotic therapy within 7 days prior to the first dose of study treatment. 2. Pregnancy or lactation. 3. Expected non-compliance. 4. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association Class III or IV), cardiac arrhythmia, or psychiatric illness. 5. Subjects who have had any anticancer treatment prior to entering the study and have not recovered to baseline (except alopecia) or = Grade 1 AEs, or deemed irreversible from the effects of prior cancer therapy. AEs > Grade 1 that are not considered a safety risk by the Sponsor and investigator may be allowed upon agreement with both. 6. Subjects with history of another primary cancer, including co-existent second malignancy, with the exception of: a) curatively resected non-melanoma skin cancer; b) curatively treated cervical carcinoma in situ; or c) other primary solid tumor with no known active disease present or in the opinion of the investigator will not affect patient outcome. 7. Subjects who had been treated with ADI-PEG 20 previously. 8. History of seizure disorder not related to underlying cancer. 9. Known HIV positivity (testing not required). 10. Known allergy to pegylated compounds. 11. Known allergy to E. coli drug products (such as GMCSF). 12. Prior grade 2 or higher neuropathy from prior platinum unless neuropathy is currently = grade 1.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The purpose of this study is to determine effectiveness of study treatment by looking at the response rate when ADI-PEG 20 is given in combination with folinic acid (leucovorin), fluorouracil and oxaliplatin (FOLFOX).;Primary end point(s): The number and percent of subjects who exhibit each level of tumor response will be summarized. Best overall response with confidence intervals will also be determined.;Secondary Objective: The secondary objectives are to determine: - Progression free survival (the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse) - Overall survival (the length of time from the start of treatment for a disease that patients diagnosed with the disease are still alive) - Duration of response (time from documentation of tumor response to disease progression) - Disease control rate (proportion of patients with reduction in tumor burden of a predefined amount) - Pharmacodynamics (how the drug affects the body)of ADI-PEG 20 in combination with FOLFOX - Pharmacokinetics (how the body affects the drug) of ADI-PEG 20 in combination with FOLFOX - Immunogenicity (ability to cause an immune response)of ADI-PEG 20 in combination with FOLFOX - Change of Alpha-fetoprotein (a type of protein associated with liver cancer);Timepoint(s) of evaluation of this end point: Scans are to be performed every 8 weeks in the week after every 8th dose of study drug for the first year of treatment, and every 12 weeks through the second year of treatment. In case of tumor response (CR, PR), repeat imaging study at 4 weeks is to be performed to confirm response. Subjects then return to scans every 8 weeks from the confirmatory scan through the first year of treatment, and then every 12 weeks in the second year of treatment. A futility analysis will be included. Futility will be assessed three times during the study based on having ORR data available for 56, 110, and 166 patients. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): PFS, OS, DoR, DCR, pharmacodynamics, pharmacokinetics, immunogenicity, and AFP will be summarized.;Timepoint(s) of evaluation of this end point: The secondary objectives of the phase 2 will be analyzed at the end of the final analysis. | — |
Countries
China, Italy, Korea, Republic of, Taiwan, United Kingdom, United States
Contacts
Public ContactWINT SWE
Polaris Pharmaceuticals, Inc.
Outcome results
None listed