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

Carcinoma, Hepatocellular Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01594125
• Other study ID #: 1199.120
• Status: Completed
• Phase: Phase 1
• First received: May 2, 2012
• Last updated: January 11, 2016
• Start date: May 2012
• Est. completion date: January 2015

Study information

• Verified date: January 2016
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: January 2015
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years and older

Eligibility

Inclusion criteria:

1. Histologically/cytologically confirmed hepatocellular carcinoma not amenable to curative surgery or loco-regional therapy

2. Age 20 years or older

3. Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1

4. Child-Pugh score of 7 or less

5. Life expectancy more than 3 months

6. Time interval from last loco-regional therapy more than 4 weeks

7. Written informed consent in accordance with good clinical practice (GCP)

Exclusion criteria:

1. More than one line of prior systemic therapy for metastatic/unresectable hepatocellular carcinoma (HCC)

2. Fibrolamellar HCC

3. Uncontrolled or refractory ascites

4. Inadequate organ function

5. Variceal bleeding within 6 months or the presence of inappropriate varices

6. History of major thrombotic (except portal vein thrombosis) or clinically relevant major bleeding event in the past 6 months

7. Major surgery within 4 weeks

8. Known inherited predisposition to bleeding or thrombosis

9. Significant cardiovascular diseases

Study Design

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular

Intervention

Drug:
• Nintedanib high dose
twice daily oral dosing
• Nintedanib low dose
twice daily oral dosing
• Nintedanib medium dose
twice daily oral dosing
• Nintedanib medium dose
twice daily oral dosing
• Nintedanib high dose
twice daily oral dosing

Locations

Country	Name	City	State
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

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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.	up to 28 months	No
Secondary	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.	up to 28 months	No
Secondary	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.	up to 28 months	No
Secondary	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.	up to 28 months	No

External Links

•   Link