Hepatocellular carcinoma
Conditions
Interventions
Product Name: Tefinostat tartrate
Product Code: CHR-2845 tartrate
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: tefinostat tartrate
Sponsors
Queen Mary, University of London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed, informed consent 2. Histologically or cytologically confirmed malignant HCC refractory to standard therapy or for which no standard therapy exists. a.Patients with alcoholic cirrhosis may be included dependent on clinical judgement as to their ability to conform to the protocol 3. Patient is not a transplant candidate 4. Recovered from all acute adverse effects of prior therapies 5. Hepatitis is controlled by antiviral therapy (PEG-IFN, ribavirin, telaprevir, etc). Prophylactic Lamivudine for HBV carriers. 6. Child-Pugh classification A or B7. 7. Adequate bone marrow, hepatic and renal function including the following a.Hb = 9.0 g/dL, absolute neutrophil count = 1.5 x 109/L, platelets =75 x 109/L b.Total bilirubin = 1.5 x upper normal limit, excluding cases where elevated bilirubin can be attributed to Gilberts Syndrome c.AST (SGOT), ALT (SGPT) = baseline + 4 x upper normal limit d.Creatinine = 1.5 x upper normal limit e.Serum albumin > 28 g/L f.INR =65 years) yes F.1.3.1 Number of subjects for this age range 35
Exclusion criteria
Exclusion criteria: 1. Anti-cancer therapy including chemotherapy, radiotherapy, TACE, endocrine therapy, immunotherapy or use of other investigational agents within the 4 weeks prior to trial. 2. Use of medicines known to prolong QTc within 14 days prior to the first dose of study drug 3. Candidate for surgical resection, orthotopic liver transplantation, or loco-regional therapy such as radio-frequency ablation or chemoembolization 4. History of organ allograft 5. Co-existing active infection or serious concurrent illness 6. Significant cardiovascular disease as defined by a.history of congestive heart failure requiring therapy b.history of unstable angina pectoris or myocardial infarction up to 6 months prior to trial entry c.presence of severe valvular heart disease d.presence of a ventricular arrhythmia requiring treatment e.LVEF CTCAE v4.0 grade I) 12. Pregnant or breast-feeding women 13. Patients who have received an investigational drug within the last 4 weeks
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase I: To determine the safety, tolerability and dose-limiting toxicities (DLT) of tefinostat when administered orally to patients with advanced HCC To determine the recommended Phase II dose (RP2D) of tefinostat in patients with advanced HCC Phase II: To perform a preliminary assessment of the anti-disease activity of tefinostat as measured by mRECIST. ; Secondary Objective: Phase I: To perform a preliminary assessment of the anti-disease activity of tefinostat as measured by mRECIST. Phase II: To determine the safety and tolerability of the recommended dose of tefinostat when administered orally to patients with advanced HCC To determine the anti-disease activity of tefinostat as measured by mRECIST Phase I and II: To determine pharmacokinetic parameters for tefinostat and CHR-2847 when administered orally at different dose levels and dose schedules To confirm monocyte specific delivery, protein acetylation will be measured in lymphocytes, granulocytes and monocytes ; Primary end point(s): Phase I: a) Causality of each AE to tefinostat and grading severity according to CTCAE 4.03. MTD at either once or twice daily dosing. b) To determine the recommended Phase II dose (RP2D) of tefinostat in patients with advanced HCC Phase II: Radiological progression free survival (RPFS) rate at 3-months ; Timepoint(s) of evaluation of this end point: Phase I: a) End of phase 1 part of study b) End of phase 1 part of study Phase II: 3 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Phase I: To perform a preliminary assessment of the anti-disease activity of tefinostat as measured by mRECIST. Phase II: a) To determine the safety and tolerability of the recommended dose of tefinostat when administered orally to patients with advanced HCC b) To determine the anti-disease activity of tefinostat as measured by mRECIST Phase I and II: a) To determine pharmacokinetic parameters for tefinostat and CHR-2847 when administered orally at different dose levels and dose schedules b) To confirm monocyte specific delivery, protein acetylation will be measured in lymphocytes, granulocytes and monocytes ; Timepoint(s) of evaluation of this end point: Phase I: End of phase 1 part of study Phase II: a) End of study b) End of study Phase I and II: a) Last patient Cycle 2 Day 1 b) End of study | — |
Countries
United Kingdom
Contacts
Public ContactDeanen Perumal
Queen Mary's, University of London
Outcome results
None listed