Dose Escalation Study of Nintedanib (BIBF 1120) in Japanese Patients With Hepatocellular Carcinoma - Full Text View

Purpose

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

Condition	Intervention	Phase
Carcinoma, Hepatocellular	Drug: Nintedanib high dose Drug: Nintedanib low dose Drug: Nintedanib medium dose	Phase 1


Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
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.

Resource links provided by NLM:

Drug Information available for: Nintedanib Nintedanib esylate

Genetic and Rare Diseases Information Center resources: Liver Cancer

U.S. FDA Resources

Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:

Determination of maximum tolerated dose (MTD) of nintedanib [ Time Frame: up to 28 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Predose (trough) and maximum measured concentration in plasma at steady state [ Time Frame: up to 2 months ] [ Designated as safety issue: No ]
Amount of drug eliminated in urine at steady state [ Time Frame: up to 1 month ] [ Designated as safety issue: No ]
Incidence and intensity of adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 [ Time Frame: up to 28 months ] [ Designated as safety issue: No ]
Area under the concentration-time curve in plasma at steady state [ Time Frame: up to 1 month ] [ Designated as safety issue: No ]
Changes of safety laboratory values from baseline [ Time Frame: up to 28 months ] [ Designated as safety issue: No ]
Incidence of hepatitis B virus (HBV) reactivation [ Time Frame: up to 28 months ] [ Designated as safety issue: No ]
Objective tumour response according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 [ Time Frame: up to 28 months ] [ Designated as safety issue: No ]
Progression free survival (PFS) [ Time Frame: up to 28 months ] [ Designated as safety issue: No ]
Time to progression (TTP) [ Time Frame: up to 28 months ] [ Designated as safety issue: No ]
Response by alpha fetoprotein (AFP) [ Time Frame: up to 28 months ] [ Designated as safety issue: No ]


Estimated Enrollment:	30
Study Start Date:	May 2012
Estimated Study Completion Date:	August 2015
Estimated Primary Completion Date:	January 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Group I patients with mild liver dysfunction according to their AST/ALT values and Child-Pugh score	Drug: Nintedanib high dose twice daily oral dosing Drug: Nintedanib medium dose twice daily oral dosing
Experimental: Group II patients with moderate liver dysfunction according to their AST/ALT values and Child-Pugh score	Drug: Nintedanib low dose twice daily oral dosing Drug: Nintedanib medium dose twice daily oral dosing Drug: Nintedanib high dose twice daily oral dosing

Eligibility


Ages Eligible for Study:	20 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01594125

Locations


Japan
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

Sponsors and Collaborators

Boehringer Ingelheim

Investigators


Study Chair:	Boehringer Ingelheim	Boehringer Ingelheim

More Information

No publications provided


Responsible Party:	Boehringer Ingelheim
ClinicalTrials.gov Identifier:	NCT01594125 History of Changes
Other Study ID Numbers:	1199.120
Study First Received:	May 2, 2012
Last Updated:	January 7, 2015
Health Authority:	Japan: Ministry of Health, Labor and Welfare

Additional relevant MeSH terms:


Carcinoma, Hepatocellular Adenocarcinoma Carcinoma Digestive System Diseases Digestive System Neoplasms Liver Diseases Liver Neoplasms Neoplasms Neoplasms by Histologic Type	Neoplasms by Site Neoplasms, Glandular and Epithelial Nintedanib Antineoplastic Agents Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Therapeutic Uses

ClinicalTrials.gov processed this record on March 03, 2015