Dose Escalation Study of Nintedanib (BIBF 1120) in Japanese Patients With Hepatocellular Carcinoma

Phase 1

Completed

• Conditions: Carcinoma, Hepatocellular
• Interventions: Drug: Nintedanib low dose; Drug: Nintedanib medium dose; Drug: Nintedanib high dose

• Registration Number: NCT01594125
• Lead Sponsor: Boehringer Ingelheim

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

Detailed Description

Not available

Study Timeline

• Study Start: 2012-05
• Study First Submitted: 2012-05-02
• Study First Submitted QC: 2012-05-07
• Study First Posted: 2012-05-08
• Primary Completion: 2014-11
• Study Completion: 2015-01
• Results First Submitted: 2015-11-17
• Results First Submitted QC: 2015-11-17
• Results First Posted: 2015-12-22
• Status Verified: 2016-01
• Last Update Submitted: 2016-01-11
• Last Update Posted: 2016-02-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

Not provided

Read More

Exclusion Criteria

Not provided

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group II	Nintedanib high dose	patients with moderate liver dysfunction according to their AST/ALT values and Child-Pugh score
Group I	Nintedanib high dose	patients with mild liver dysfunction according to their AST/ALT values and Child-Pugh score
Group I	Nintedanib medium dose	patients with mild liver dysfunction according to their AST/ALT values and Child-Pugh score
Group II	Nintedanib low dose	patients with moderate liver dysfunction according to their AST/ALT values and Child-Pugh score
Group II	Nintedanib medium dose	patients with moderate liver dysfunction according to their AST/ALT values and Child-Pugh score

Primary Outcome Measures

Name	Time	Method
Number of Participants With Dose Limiting Toxicities to Determine Maximum Tolerated Dose (MTD) of Nintedanib	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 Outcome Measures

Name	Time	Method
Number of Participants With Objective Tumour Response According to Response Evaluation Criteria in Solid Tumors (RECIST) 1.0	up to 28 months	Objective response (Complete response (CR) + Partial response (PR), regardless of confirmation) is derived from a patient's best objective response by RECIST. Best objective response is calculated based on the "overall" visit response from each assessment. Best objective response represents the best response a patient has had during their time in the study up until progression, last evaluable assessment in the absence of progression or the start of subsequent anti-cancer therapy. For patients whose progression event is death, best objective response will be calculated based on data up until the last evaluable RECIST assessment prior to death.
Progression Free Survival (PFS)	up to 28 months	PFS is defined as the duration from start date of the study treatment to PD according to RECIST 1.0, or any death whichever occurs earlier.
Time to Progression (TTP)	up to 28 months	TTP is defined as the duration from the start date of the study treatment to PD according to RECIST 1.0.
Number of Participants With Response by Alpha Fetoprotein (AFP)	up to 28 months	Response by AFP is defined as 20% or more decline in AFP between the baseline value and the AFP value after three courses (12 weeks) of therapy. If patients only receive two courses of therapy the AFP value after two courses (8 weeks) will be used for the analysis.

Trial Locations

Locations (5)

1199.120.001 Boehringer Ingelheim Investigational Site; 🇯🇵 Chuo-ku, Tokyo, Japan

1199.120.005 Boehringer Ingelheim Investigational Site; 🇯🇵 Fukuoka, Fukuoka, Japan

1199.120.003 Boehringer Ingelheim Investigational Site; 🇯🇵 Nagoya, Aichi, Japan

1199.120.004 Boehringer Ingelheim Investigational Site; 🇯🇵 Saga, Saga, Japan

1199.120.002 Boehringer Ingelheim Investigational Site; 🇯🇵 Kashiwa, Chiba, Japan