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

This study has been completed.
Sponsor:
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
  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
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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

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
Adenocarcinoma
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 April 27, 2016