Dose Escalation Study of Nintedanib (BIBF 1120) in Japanese Patients With Hepatocellular Carcinoma
This study has been completed.
Sponsor:
Boehringer Ingelheim
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01594125
First received: May 2, 2012
Last updated: January 11, 2016
Last verified: January 2016
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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:
Further study details as provided by Boehringer Ingelheim:
Primary Outcome Measures:
- Number of Participants With Dose Limiting Toxicities to Determine Maximum Tolerated Dose (MTD) of Nintedanib [ Time Frame: up to 28 days ] [ Designated as safety issue: No ]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 [ Time Frame: up to 28 months ] [ Designated as safety issue: No ]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) [ Time Frame: up to 28 months ] [ Designated as safety issue: No ]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) [ Time Frame: up to 28 months ] [ Designated as safety issue: No ]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) [ Time Frame: up to 28 months ] [ Designated as safety issue: No ]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.
| Enrollment: | 30 |
| Study Start Date: | May 2012 |
| Study Completion Date: | January 2015 |
| Primary Completion Date: | November 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 (Adult, Senior) |
| 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
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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
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
Additional Information:
| Responsible Party: | Boehringer Ingelheim |
| ClinicalTrials.gov Identifier: | NCT01594125 History of Changes |
| Other Study ID Numbers: | 1199.120 |
| Study First Received: | May 2, 2012 |
| Results First Received: | November 17, 2015 |
| Last Updated: | January 11, 2016 |
| 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 Nintedanib Antineoplastic Agents Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |
ClinicalTrials.gov processed this record on September 23, 2016