Dose Escalation Study of Nintedanib (BIBF 1120) in Japanese Patients With Hepatocellular Carcinoma
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.
1 other identifier
interventional
30
1 country
5
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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started May 2012
Typical duration for phase_1
5 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
May 1, 2012
CompletedFirst Submitted
Initial submission to the registry
May 2, 2012
CompletedFirst Posted
Study publicly available on registry
May 8, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
January 1, 2015
CompletedResults Posted
Study results publicly available
December 22, 2015
CompletedFebruary 12, 2016
January 1, 2016
2.5 years
May 2, 2012
November 17, 2015
January 11, 2016
Conditions
Outcome Measures
Primary Outcomes (1)
Number of Participants With Dose Limiting Toxicities to Determine Maximum Tolerated Dose (MTD) of Nintedanib
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.
up to 28 days
Secondary Outcomes (4)
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
Study Arms (2)
Group I
EXPERIMENTALpatients with mild liver dysfunction according to their AST/ALT values and Child-Pugh score
Group II
EXPERIMENTALpatients with moderate liver dysfunction according to their AST/ALT values and Child-Pugh score
Interventions
Eligibility Criteria
You may qualify if:
- Histologically/cytologically confirmed hepatocellular carcinoma not amenable to curative surgery or loco-regional therapy
- Age 20 years or older
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1
- Child-Pugh score of 7 or less
- Life expectancy more than 3 months
- Time interval from last loco-regional therapy more than 4 weeks
- Written informed consent in accordance with good clinical practice (GCP)
You may not qualify if:
- More than one line of prior systemic therapy for metastatic/unresectable hepatocellular carcinoma (HCC)
- Fibrolamellar HCC
- Uncontrolled or refractory ascites
- Inadequate organ function
- Variceal bleeding within 6 months or the presence of inappropriate varices
- History of major thrombotic (except portal vein thrombosis) or clinically relevant major bleeding event in the past 6 months
- Major surgery within 4 weeks
- Known inherited predisposition to bleeding or thrombosis
- Significant cardiovascular diseases
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (5)
1199.120.001 Boehringer Ingelheim Investigational Site
Chuo-ku, Tokyo, Japan
1199.120.005 Boehringer Ingelheim Investigational Site
Fukuoka, Fukuoka, Japan
1199.120.002 Boehringer Ingelheim Investigational Site
Kashiwa, Chiba, Japan
1199.120.003 Boehringer Ingelheim Investigational Site
Nagoya, Aichi, Japan
1199.120.004 Boehringer Ingelheim Investigational Site
Saga, Saga, Japan
Related Publications (1)
Okusaka T, Otsuka T, Ueno H, Mitsunaga S, Sugimoto R, Muro K, Saito I, Tadayasu Y, Inoue K, Loembe AB, Ikeda M. Phase I study of nintedanib in Japanese patients with advanced hepatocellular carcinoma and liver impairment. Cancer Sci. 2016 Dec;107(12):1791-1799. doi: 10.1111/cas.13077. Epub 2016 Dec 12.
PMID: 27627050DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Boehringer Ingelheim, Call Center
- Organization
- Boehringer Ingelheim
Study Officials
- STUDY CHAIR
Boehringer Ingelheim
Boehringer Ingelheim
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 2, 2012
First Posted
May 8, 2012
Study Start
May 1, 2012
Primary Completion
November 1, 2014
Study Completion
January 1, 2015
Last Updated
February 12, 2016
Results First Posted
December 22, 2015
Record last verified: 2016-01