Dose Escalation Study for 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:

MedlinePlus related topics: Cancer

U.S. FDA Resources

Further study details as provided by Boehringer Ingelheim Pharmaceuticals:

Primary Outcome Measures:

Determination of maximum tolerated dose (MTD) of nintedanib [ Time Frame: up to 1 month ] [ Designated as safety issue: Yes ]

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 ]
Terminal rate constant in plasma at steady state [ Time Frame: up to 1 month ] [ Designated as safety issue: No ]
Time from last dosing to the maximum concentration in plasma at steady state [ Time Frame: up to 1 month ] [ Designated as safety issue: No ]
Mean residence time in the body at steady state after administration [ Time Frame: up to 1 month ] [ Designated as safety issue: No ]
Apparent clearance in plasma at steady state [ Time Frame: up to 1 month ] [ Designated as safety issue: No ]
Apparent volume of distribution during the terminal phase at steady state [ Time Frame: up to 1 month ] [ 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 ]
Terminal half-life in plasma 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 12 months ] [ Designated as safety issue: Yes ]
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 12 months ] [ Designated as safety issue: Yes ]
Incidence of hepatitis B virus (HBV) reactivation [ Time Frame: up to 12 months ] [ Designated as safety issue: Yes ]
Objective tumour response according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 [ Time Frame: up to 12 months ] [ Designated as safety issue: No ]
Progression free survival (PFS) [ Time Frame: up to 12 months ] [ Designated as safety issue: No ]
Time to progression (TTP) [ Time Frame: up to 12 months ] [ Designated as safety issue: No ]
Response by alpha fetoprotein (AFP) [ Time Frame: up to 12 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	24
Study Start Date:	May 2012
Estimated Study Completion Date:	August 2014
Estimated Primary Completion Date:	March 2014 (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

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

Contacts

Contact: Boehringer Ingelheim Call Center

1-800-243-0127

clintriage.rdg@boehringer-ingelheim.com

Locations

Japan
1199.120.001 Boehringer Ingelheim Investigational Site	Recruiting
Chuo-ku, Tokyo, Japan
1199.120.002 Boehringer Ingelheim Investigational Site	Recruiting
Kashiwa, Chiba, Japan
1199.120.003 Boehringer Ingelheim Investigational Site	Recruiting
Nagoya, Aichi, Japan

Sponsors and Collaborators

Boehringer Ingelheim Pharmaceuticals

Investigators

Study Chair:

Boehringer Ingelheim

Boehringer Ingelheim Pharmaceuticals

More Information

No publications provided

Responsible Party:	Boehringer Ingelheim Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT01594125 History of Changes
Other Study ID Numbers:	1199.120
Study First Received:	May 2, 2012
Last Updated:	June 12, 2013
Health Authority:	Japan: Ministry of Health, Labor and Welfare

Additional relevant MeSH terms:

Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma

Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases

ClinicalTrials.gov processed this record on June 18, 2013