An Open Label, Dose Escalation Phase I Study to Evaluate the Safety and Tolerability of Continuous Twice-daily Oral Treatment of Nintedanib in Japanese Patients With Hepatocellular Carcinoma.
Overview
- Phase
- Phase 1
- Intervention
- Nintedanib medium dose
- Conditions
- Carcinoma, Hepatocellular
- Sponsor
- Boehringer Ingelheim
- Enrollment
- 30
- Locations
- 5
- Primary Endpoint
- Number of Participants With Dose Limiting Toxicities to Determine Maximum Tolerated Dose (MTD) of Nintedanib
- Status
- Completed
- Last Updated
- 10 years ago
Overview
Brief Summary
The aim of the study is to investigate the safety, tolerability, efficacy and pharmacokinetics (PK) for Japanese hepatocellular carcinoma which are not amenable to curative surgery or loco regional therapy
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Group I
patients with mild liver dysfunction according to their AST/ALT values and Child-Pugh score
Intervention: Nintedanib medium dose
Group I
patients with mild liver dysfunction according to their AST/ALT values and Child-Pugh score
Intervention: Nintedanib high dose
Group II
patients with moderate liver dysfunction according to their AST/ALT values and Child-Pugh score
Intervention: Nintedanib low dose
Group II
patients with moderate liver dysfunction according to their AST/ALT values and Child-Pugh score
Intervention: Nintedanib medium dose
Group II
patients with moderate liver dysfunction according to their AST/ALT values and Child-Pugh score
Intervention: Nintedanib high dose
Outcomes
Primary Outcomes
Number of Participants With Dose Limiting Toxicities to Determine Maximum Tolerated Dose (MTD) of Nintedanib
Time Frame: up to 28 days
The MTD is based on the incidence of Dose Limiting Toxicities (DLTs). A drug-related AE was considered as a DLT if one of the following met: CTCAE grade 4 thrombocytopenia of any duration, CTCAE grade 4 neutropenia lasting for ≥8 days, CTCAE grade 4 febrile neutropenia of any duration, CTCAE grade 3 or 4 non-haematologic toxicity (with the following exception: Alopecia, Vomiting, nausea, or diarrhoea with no adequate supportive care, Transient electrolyte abnormality, which resolves spontaneously or can be corrected with appropriate treatment within 3 days, Liver toxicity), Liver enzyme toxicity of AST, ALT, alkaline phosphatase \[ALP\] elevation \>5x ULN, or total bilirubin \>3x ULN if baseline liver enzymes are within the normal range, or AST, ALT or ALP \> baseline value + 4x ULN if the baseline value is elevated. The MTD was determined to be 200mg bid.
Secondary Outcomes
- Number of Participants With Objective Tumour Response According to Response Evaluation Criteria in Solid Tumors (RECIST) 1.0(up to 28 months)
- Progression Free Survival (PFS)(up to 28 months)
- Time to Progression (TTP)(up to 28 months)
- Number of Participants With Response by Alpha Fetoprotein (AFP)(up to 28 months)