Dose Escalation Study of Nintedanib (BIBF 1120) in Japanese Patients With Hepatocellular Carcinoma
Primary Purpose
Carcinoma, Hepatocellular
Status
Completed
Phase
Phase 1
Locations
Japan
Study Type
Interventional
Intervention
Nintedanib high dose
Nintedanib low dose
Nintedanib medium dose
Nintedanib medium dose
Nintedanib high dose
Sponsored by

About this trial
This is an interventional treatment trial for Carcinoma, Hepatocellular
Eligibility Criteria
Inclusion criteria:
- 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)
Exclusion criteria:
- 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
Sites / Locations
- 1199.120.001 Boehringer Ingelheim Investigational Site
- 1199.120.005 Boehringer Ingelheim Investigational Site
- 1199.120.002 Boehringer Ingelheim Investigational Site
- 1199.120.003 Boehringer Ingelheim Investigational Site
- 1199.120.004 Boehringer Ingelheim Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Group I
Group II
Arm Description
patients with mild liver dysfunction according to their AST/ALT values and Child-Pugh score
patients with moderate liver dysfunction according to their AST/ALT values and Child-Pugh score
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Number of Participants With Objective Tumour Response According to Response Evaluation Criteria in Solid Tumors (RECIST) 1.0
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)
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)
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)
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01594125
Brief Title
Dose Escalation Study of Nintedanib (BIBF 1120) in Japanese Patients With Hepatocellular Carcinoma
Official Title
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.
Study Type
Interventional
2. Study Status
Record Verification Date
January 2016
Overall Recruitment Status
Completed
Study Start Date
May 2012 (undefined)
Primary Completion Date
November 2014 (Actual)
Study Completion Date
January 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Boehringer Ingelheim
4. Oversight
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma, Hepatocellular
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group I
Arm Type
Experimental
Arm Description
patients with mild liver dysfunction according to their AST/ALT values and Child-Pugh score
Arm Title
Group II
Arm Type
Experimental
Arm Description
patients with moderate liver dysfunction according to their AST/ALT values and Child-Pugh score
Intervention Type
Drug
Intervention Name(s)
Nintedanib high dose
Intervention Description
twice daily oral dosing
Intervention Type
Drug
Intervention Name(s)
Nintedanib low dose
Intervention Description
twice daily oral dosing
Intervention Type
Drug
Intervention Name(s)
Nintedanib medium dose
Intervention Description
twice daily oral dosing
Intervention Type
Drug
Intervention Name(s)
Nintedanib medium dose
Intervention Description
twice daily oral dosing
Intervention Type
Drug
Intervention Name(s)
Nintedanib high dose
Intervention Description
twice daily oral dosing
Primary Outcome Measure Information:
Title
Number of Participants With Dose Limiting Toxicities to Determine Maximum Tolerated Dose (MTD) of Nintedanib
Description
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.
Time Frame
up to 28 days
Secondary Outcome Measure Information:
Title
Number of Participants With Objective Tumour Response According to Response Evaluation Criteria in Solid Tumors (RECIST) 1.0
Description
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.
Time Frame
up to 28 months
Title
Progression Free Survival (PFS)
Description
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 Frame
up to 28 months
Title
Time to Progression (TTP)
Description
TTP is defined as the duration from the start date of the study treatment to PD according to RECIST 1.0.
Time Frame
up to 28 months
Title
Number of Participants With Response by Alpha Fetoprotein (AFP)
Description
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.
Time Frame
up to 28 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria:
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)
Exclusion criteria:
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Boehringer Ingelheim
Organizational Affiliation
Boehringer Ingelheim
Official's Role
Study Chair
Facility Information:
Facility Name
1199.120.001 Boehringer Ingelheim Investigational Site
City
Chuo-ku, Tokyo
Country
Japan
Facility Name
1199.120.005 Boehringer Ingelheim Investigational Site
City
Fukuoka, Fukuoka
Country
Japan
Facility Name
1199.120.002 Boehringer Ingelheim Investigational Site
City
Kashiwa, Chiba
Country
Japan
Facility Name
1199.120.003 Boehringer Ingelheim Investigational Site
City
Nagoya, Aichi
Country
Japan
Facility Name
1199.120.004 Boehringer Ingelheim Investigational Site
City
Saga, Saga
Country
Japan
12. IPD Sharing Statement
Citations:
PubMed Identifier
27627050
Citation
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.
Results Reference
derived
Links:
URL
http://trials.boehringer-ingelheim.com
Description
Related Info
Learn more about this trial
Dose Escalation Study of Nintedanib (BIBF 1120) in Japanese Patients With Hepatocellular Carcinoma
We'll reach out to this number within 24 hrs