A Phase I / II Trial of Nintedanib in Asian Hepatocellular Carcinoma Patients

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00987935
First received: September 30, 2009
Last updated: July 31, 2015
Last verified: July 2015
  Purpose

This study is to evaluate the safety, appropriate dose, and efficacy of BIBF 1120 in liver cancer patients


Condition Intervention Phase
Carcinoma, Hepatocellular
Drug: Sorafenib
Drug: BIBF 1120
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter, Open Label, Phase I/Randomized II Study to Evaluate Safety, Pharmacokinetics and Efficacy of BIBF 1120 in Comparison With Sorafenib for Advanced Hepatocellular Carcinoma Patients in Asia.

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Maximum Tolerated Dose in Phase I [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    The MTD was defined as the highest dose studied for which the incidence of DLTs was 0/3 or less than 2/6 patients during the first treatment course.

  • Time to Progression (TTP) in Phase II [ Time Frame: From randomization until data cut-off (28 Sep 2012); Up to 77 weeks ] [ Designated as safety issue: No ]
    TTP according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.0 criteria based on central independent review. TTP RECIST 1.0 was defined as the time from randomisation to disease progression according to RECIST 1.0.


Secondary Outcome Measures:
  • Time to Progression (TTP) in Phase II (Follow-up Analyses) [ Time Frame: From randomization until disease progression or data cut-off (16 Jul 2014); Up to 171 weeks ] [ Designated as safety issue: No ]
    TTP according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.0 criteria based on central independent review. TTP RECIST 1.0 was defined as the time from randomisation to disease progression according to RECIST 1.0.

  • Incidence and Intensity of Adverse Events (AEs) Reported as the Number of Patients With AEs According to Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 Throughout the Treatment Period. [ Time Frame: AEs with an onset during therapy with study treatment or within 28 days after discontinuation of study treatment (up to 1066 days) ] [ Designated as safety issue: No ]
    Incidence and worst intensity (severity) of Adverse Events with grading according to the Common Terminology Criteria for Adverse Events (CTCAE version 3.0).

  • Incidence of Dose Limiting Toxicity in Phase I [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Number of patients with dose limiting toxicity are presented

  • Objective Tumour Response by RECIST [ Time Frame: From randomization until data cut-off (16 July 2014); Up to 171 weeks ] [ Designated as safety issue: No ]

    Objective RECIST 1.0 tumour response was defined as Complete Response (CR) or Partial Response (PR) and was derived from the patient's best objective RECIST 1.0 response based on central independent review.

    95% Confidence Interval presented below are computed by Clopper and Pearson method.


  • Progression Free Survival (PFS) [ Time Frame: From randomization until data cut-off (16 July 2014); Up to 171 weeks ] [ Designated as safety issue: No ]
    PFS by RECIST 1.0 was defined as the duration from date of randomisation to date of progression or death, whichever occurred earlier, based on central independent review.

  • Overall Survival [ Time Frame: From randomization until data cut-off (16 July 2014); Up to 171 weeks ] [ Designated as safety issue: No ]
    Overall survival was defined as the duration from date of randomisation to the date of death.

  • AUC0-12,ss,Norm (Area Under the Plasma Concentration-time Curve Between 0 and 12 Hours at Steady State, Normalised Values) of Nintedanib [ Time Frame: Day1, Day15 and Day 16 ] [ Designated as safety issue: No ]

    AUC0-12,ss,norm (area under the plasma concentration-time curve between 0 and 12 hours at steady state, normalised values) of Nintedanib

    Detailed time points of sampling are:

    Phase I and selected phase II patients in the Nintedanib arm:

    Cycle 1, Day 15 to 16: Immediately prior to swallowing the dose of nintedanib (predose) and 1 hour (h), 2 h, 3 h, 4 h, 5 h, 7 h, 10 h, 12 h and 24 h after drug administration on Day 15; Cycle 2, Day 1: Immediately prior to swallowing the dose of nintedanib (predose) and 2 h after drug administration on Day 1; Cycle 2, Day 15: Immediately prior to swallowing the dose of nintedanib (predose) and 2 h after drug administration on Day 15.


  • AUC0-12,ss,Norm (Area Under the Plasma Concentration-time Curve Between 0 and 12 Hours at Steady State, Normalised Values) of BIBF 1202 (Metabolite of Nintedanib) [ Time Frame: Day1, Day15 and Day 16 ] [ Designated as safety issue: No ]

    AUC0-12,ss,norm (area under the plasma concentration-time curve between 0 and 12 hours at steady state, normalised values) of BIBF 1202 (metabolite of Nintedanib).

    Detailed time points of sampling are:

    Phase I and selected phase II patients in the Nintedanib arm:

    Cycle 1, Day 15 to 16: Immediately prior to swallowing the dose of nintedanib (predose) and 1 hour (h), 2 h, 3 h, 4 h, 5 h, 7 h, 10 h, 12 h and 24 h after drug administration on Day 15; Cycle 2, Day 1: Immediately prior to swallowing the dose of nintedanib (predose) and 2 h after drug administration on Day 1; Cycle 2, Day 15: Immediately prior to swallowing the dose of nintedanib (predose) and 2 h after drug administration on Day 15.


  • AUC0-12,ss,Norm (Area Under the Plasma Concentration-time Curve Between 0 and 12 Hours at Steady State, Normalised Values) of BIBF 1202 Glucuronide (Metabolite of Nintedanib) [ Time Frame: Day1, Day15 and Day 16 ] [ Designated as safety issue: No ]

    AUC0-12,ss,norm of BIBF 1202 glucuronide (Metabolite of Nintedanib):

    Detailed time points of sampling are:

    Phase I and selected phase II patients in the Nintedanib arm:

    Cycle 1, Day 15 to 16: Immediately prior to swallowing the dose of nintedanib (predose) and 1 hour (h), 2 h, 3 h, 4 h, 5 h, 7 h, 10 h, 12 h and 24 h after drug administration on Day 15; Cycle 2, Day 1: Immediately prior to swallowing the dose of nintedanib (predose) and 2 h after drug administration on Day 1; Cycle 2, Day 15: Immediately prior to swallowing the dose of nintedanib (predose) and 2 h after drug administration on Day 15.


  • Cmax,ss,Norm (Maximum Concentration of the Nintedanib in Plasma at Steady State, Normalised Values) [ Time Frame: Day1, Day15 and Day 16 ] [ Designated as safety issue: No ]

    Cmax,ss,norm (maximum concentration of the Nintedanib in plasma at steady state, normalised values).

    Detailed time points of sampling are:

    Phase I and selected phase II patients in the Nintedanib arm:

    Cycle 1, Day 15 to 16: Immediately prior to swallowing the dose of nintedanib (predose) and 1 hour (h), 2 h, 3 h, 4 h, 5 h, 7 h, 10 h, 12 h and 24 h after drug administration on Day 15; Cycle 2, Day 1: Immediately prior to swallowing the dose of nintedanib (predose) and 2 h after drug administration on Day 1; Cycle 2, Day 15: Immediately prior to swallowing the dose of nintedanib (predose) and 2 h after drug administration on Day 15.


  • Cmax,ss,Norm (Maximum Concentration of the BIBF 1202 in Plasma at Steady State, Normalised Values) [ Time Frame: Day1, Day15 and Day 16 ] [ Designated as safety issue: No ]

    Cmax,ss,norm (maximum concentration of the BIBF 1202 in plasma at steady state, normalised values).

    Detailed time points of sampling are:

    Phase I and selected phase II patients in the Nintedanib arm:

    Cycle 1, Day 15 to 16: Immediately prior to swallowing the dose of nintedanib (predose) and 1 hour (h), 2 h, 3 h, 4 h, 5 h, 7 h, 10 h, 12 h and 24 h after drug administration on Day 15; Cycle 2, Day 1: Immediately prior to swallowing the dose of nintedanib (predose) and 2 h after drug administration on Day 1; Cycle 2, Day 15: Immediately prior to swallowing the dose of nintedanib (predose) and 2 h after drug administration on Day 15.


  • Cmax,ss,Norm (Maximum Concentration of the BIBF 1202 Glucuronide in Plasma at Steady State, Normalised Values) [ Time Frame: Day1, Day15 and Day 16 ] [ Designated as safety issue: No ]

    Cmax,ss,norm (maximum concentration of the BIBF 1202 glucuronide in plasma at steady state, normalised values).

    Detailed time points of sampling are:

    Phase I and selected phase II patients in the Nintedanib arm:

    Cycle 1, Day 15 to 16: Immediately prior to swallowing the dose of nintedanib (predose) and 1 hour (h), 2 h, 3 h, 4 h, 5 h, 7 h, 10 h, 12 h and 24 h after drug administration on Day 15; Cycle 2, Day 1: Immediately prior to swallowing the dose of nintedanib (predose) and 2 h after drug administration on Day 1; Cycle 2, Day 15: Immediately prior to swallowing the dose of nintedanib (predose) and 2 h after drug administration on Day 15.


  • fe0-12,ss (Fraction Excreted in Urine Between 0 and 12 Hours at Steady State) for Nintedanib [ Time Frame: 0 to 4 hours (h), 4 to 12 h, and 12 to 24 h after nintedanib ] [ Designated as safety issue: No ]

    fe0-12,ss (fraction excreted in urine between 0 and 12 hours at steady state) for Nintedanib.

    The reported value corresponds to the percentage of administered dose.



Enrollment: 134
Study Start Date: October 2009
Estimated Study Completion Date: December 2015
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Nintedanib (BIBF 1120)
Phase I dose escalation and phase II using dose determined in phase I
Drug: BIBF 1120
Twice daily
Active Comparator: Sorafenib
Twice daily dosing in phase II
Drug: Sorafenib
400 mg twice daily

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. Hepatocellular carcinoma, either histologically/cytologically confirmed or clinically diagnosed, which is not amenable to curative surgery or loco-regional therapy
  2. Age 18 years or older
  3. Eastern Cooperative Group performance score of 2 or less
  4. Child-Pugh score of 7 or less
  5. Written informed consent in accordance with International Conference on Harmonisation (ICH) and Good Clinical Practice (GCP) and local legislation

Exclusion criteria:

  1. Prior systemic therapy for metastatic/unresectable hepatocellular carcinoma (for phase II)
  2. More than one line of prior systemic therapy for metastatic/unresectable hepatocellular carcinoma (for phase I)
  3. Uncontrolled or refractory ascites to adequate medical therapy
  4. Bilirubin greater than 1.5 times upper limit of normal
  5. Aspartate amino transferase or alanine amino transferase greater than 5 times upper limit of normal
  6. Absolute neutrophil count less than 1500/microliter
  7. Platelet count less than 75000/microliter
  8. Hemoglobin less than 9 g/dL
  9. Serum creatinine greater than 1.5 times upper limit of normal
  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: NCT00987935

Locations
Korea, Republic of
1199.39.82006 Boehringer Ingelheim Investigational Site
Seoul, Korea, Republic of
1199.39.82002 Boehringer Ingelheim Investigational Site
Seoul, Korea, Republic of
1199.39.82001 Boehringer Ingelheim Investigational Site
Seoul, Korea, Republic of
1199.39.82004 Boehringer Ingelheim Investigational Site
Seoul, Korea, Republic of
1199.39.82005 Boehringer Ingelheim Investigational Site
Seoul, Korea, Republic of
1199.39.82003 Boehringer Ingelheim Investigational Site
Seoul, Korea, Republic of
Taiwan
1199.39.88606 Boehringer Ingelheim Investigational Site
Changhua, Taiwan
1199.39.88609 Boehringer Ingelheim Investigational Site
Kaohsiung, Taiwan
1199.39.88610 Boehringer Ingelheim Investigational Site
Kaohsiung, Taiwan
1199.39.88605 Boehringer Ingelheim Investigational Site
Taichung, Taiwan
1199.39.88602 Boehringer Ingelheim Investigational Site
Tainan, Taiwan
1199.39.88608 Boehringer Ingelheim Investigational Site
Tainan City, Taiwan
1199.39.88601 Boehringer Ingelheim Investigational Site
Taipei, Taiwan
1199.39.88603 Boehringer Ingelheim Investigational Site
Taipei, Taiwan
1199.39.88604 Boehringer Ingelheim Investigational Site
Taoyuan County, Taiwan
1199.39.88607 Boehringer Ingelheim Investigational Site
Yunlin County, Taiwan
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00987935     History of Changes
Other Study ID Numbers: 1199.39
Study First Received: September 30, 2009
Results First Received: June 3, 2015
Last Updated: July 31, 2015
Health Authority: South Korea: Ministry of Food and Drug Safety (MFDS)
Taiwan: Department of Health
United States: Food and Drug Administration

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
Sorafenib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on September 02, 2015