A Phase I / II Trial of Nintedanib in Asian Hepatocellular Carcinoma Patients
- Registration Number
- NCT00987935
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
This study is to evaluate the safety, appropriate dose, and efficacy of BIBF 1120 in liver cancer patients
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 134
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Nintedanib (BIBF 1120) BIBF 1120 Phase I dose escalation and phase II using dose determined in phase I Sorafenib Sorafenib Twice daily dosing in phase II
- Primary Outcome Measures
Name Time Method Maximum Tolerated Dose in Phase I 4 weeks 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 From randomization until data cut-off (28 Sep 2012); Up to 77 weeks 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
Name Time Method Progression Free Survival (PFS) From randomization until data cut-off (16 July 2014); Up to 171 weeks 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 From randomization until data cut-off (16 July 2014); Up to 171 weeks Overall survival was defined as the duration from date of randomisation to the date of death.
fe0-12,ss (Fraction Excreted in Urine Between 0 and 12 Hours at Steady State) for Nintedanib 0 to 4 hours (h), 4 to 12 h, and 12 to 24 h after nintedanib 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.Time to Progression (TTP) in Phase II (Follow-up Analyses) From randomization until disease progression or data cut-off (16 Jul 2014); Up to 171 weeks 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. AEs with an onset during therapy with study treatment or within 28 days after discontinuation of study treatment (up to 1066 days) 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 4 weeks Number of patients with dose limiting toxicity are presented
AUC0-12,ss,Norm (Area Under the Plasma Concentration-time Curve Between 0 and 12 Hours at Steady State, Normalised Values) of Nintedanib Day1, Day15 and Day 16 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.Objective Tumour Response by RECIST From randomization until data cut-off (16 July 2014); Up to 171 weeks 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.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) Day1, Day15 and Day 16 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) Day1, Day15 and Day 16 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) Day1, Day15 and Day 16 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) Day1, Day15 and Day 16 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) Day1, Day15 and Day 16 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.
Trial Locations
- Locations (16)
1199.39.88604 Boehringer Ingelheim Investigational Site
🇨🇳Taoyuan County, Taiwan
1199.39.88606 Boehringer Ingelheim Investigational Site
🇨🇳Changhua, Taiwan
1199.39.88603 Boehringer Ingelheim Investigational Site
🇨🇳Taipei, Taiwan
1199.39.88605 Boehringer Ingelheim Investigational Site
🇨🇳Taichung, Taiwan
1199.39.88601 Boehringer Ingelheim Investigational Site
🇨🇳Taipei, Taiwan
1199.39.88607 Boehringer Ingelheim Investigational Site
🇨🇳Yunlin County, Taiwan
1199.39.82004 Boehringer Ingelheim Investigational Site
🇰🇷Seoul, Korea, Republic of
1199.39.82006 Boehringer Ingelheim Investigational Site
🇰🇷Seoul, Korea, Republic of
1199.39.82001 Boehringer Ingelheim Investigational Site
🇰🇷Seoul, Korea, Republic of
1199.39.82002 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
1199.39.88609 Boehringer Ingelheim Investigational Site
🇨🇳Kaohsiung, Taiwan
1199.39.88610 Boehringer Ingelheim Investigational Site
🇨🇳Kaohsiung, Taiwan
1199.39.88608 Boehringer Ingelheim Investigational Site
🇨🇳Tainan City, Taiwan
1199.39.88602 Boehringer Ingelheim Investigational Site
🇨🇳Tainan, Taiwan