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

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ClinicalTrials.gov Identifier: NCT01594125
Recruitment Status : Completed
First Posted : May 8, 2012
Results First Posted : December 22, 2015
Last Update Posted : February 12, 2016
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Study Description
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Brief 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

Condition or disease Intervention/treatment Phase
Carcinoma, Hepatocellular Drug: Nintedanib high dose Drug: Nintedanib low dose Drug: Nintedanib medium dose Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (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.
Study Start Date : May 2012
Actual Primary Completion Date : November 2014
Actual Study Completion Date : January 2015

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Arms and Interventions
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Arm Intervention/treatment
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


Outcome Measures
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Primary Outcome Measures :
  1. Number of Participants With Dose Limiting Toxicities to Determine Maximum Tolerated Dose (MTD) of Nintedanib [ Time Frame: up to 28 days ]
    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 :
  1. Number of Participants With Objective Tumour Response According to Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 [ Time Frame: up to 28 months ]
    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.

  2. Progression Free Survival (PFS) [ Time Frame: up to 28 months ]
    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.

  3. Time to Progression (TTP) [ Time Frame: up to 28 months ]
    TTP is defined as the duration from the start date of the study treatment to PD according to RECIST 1.0.

  4. Number of Participants With Response by Alpha Fetoprotein (AFP) [ Time Frame: up to 28 months ]
    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.


Eligibility Criteria
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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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
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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01594125


Locations
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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
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Study Chair: Boehringer Ingelheim Boehringer Ingelheim
More Information
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Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01594125    
Other Study ID Numbers: 1199.120
First Posted: May 8, 2012    Key Record Dates
Results First Posted: December 22, 2015
Last Update Posted: February 12, 2016
Last Verified: January 2016
Additional relevant MeSH terms:
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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