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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

May 2, 2012
January 11, 2016
May 2012
November 2014   (final data collection date for primary outcome measure)
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.
Determination of Maximum Tolerated Dose (MTD) of Nintedanib [ Time Frame: up to 1 month ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01594125 on ClinicalTrials.gov Archive Site
  • 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.
  • 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 ]
Not Provided
Not Provided
 
Dose Escalation Study of Nintedanib (BIBF 1120) in Japanese Patients With Hepatocellular Carcinoma
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.
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
Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Carcinoma, Hepatocellular
  • Drug: Nintedanib high dose
    twice daily oral dosing
  • Drug: Nintedanib low dose
    twice daily oral dosing
  • Drug: Nintedanib medium dose
    twice daily oral dosing
  • Experimental: Group I
    patients with mild liver dysfunction according to their AST/ALT values and Child-Pugh score
    Interventions:
    • Drug: Nintedanib high dose
    • Drug: Nintedanib medium dose
  • Experimental: Group II
    patients with moderate liver dysfunction according to their AST/ALT values and Child-Pugh score
    Interventions:
    • Drug: Nintedanib low dose
    • Drug: Nintedanib medium dose
    • Drug: Nintedanib high dose
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
30
January 2015
November 2014   (final data collection date for primary outcome measure)

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
Both
20 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Japan
 
NCT01594125
1199.120
Not Provided
Not Provided
Not Provided
Boehringer Ingelheim
Boehringer Ingelheim
Not Provided
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
Boehringer Ingelheim
January 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP