Clinical trial NCT00987935: A Phase I / II Trial of Nintedanib in Asian Hepatocellular Carcinoma Patients
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Carcinoma, Hepatocellular
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2009-10-01
Enrollment: 134
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility 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

Primary outcomes:
measure: Maximum Tolerated Dose in Phase I
timeFrame: 4 weeks
measure: Time to Progression (TTP) in Phase II
timeFrame: From randomization until data cut-off (28 Sep 2012); Up to 77 weeks
Secondary outcomes:
measure: Time to Progression (TTP) in Phase II (Follow-up Analyses)
timeFrame: From randomization until disease progression or data cut-off (16 Jul 2014); Up to 171 weeks
measure: 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.
timeFrame: AEs with an onset during therapy with study treatment or within 28 days after discontinuation of study treatment (up to 1066 days)
measure: Incidence of Dose Limiting Toxicity in Phase I
timeFrame: 4 weeks
measure: Objective Tumour Response by RECIST
timeFrame: From randomization until data cut-off (16 July 2014); Up to 171 weeks
measure: Progression Free Survival (PFS)
timeFrame: From randomization until data cut-off (16 July 2014); Up to 171 weeks
measure: Overall Survival
timeFrame: From randomization until data cut-off (16 July 2014); Up to 171 weeks
measure: AUC0-12,ss,Norm (Area Under the Plasma Concentration-time Curve Between 0 and 12 Hours at Steady State, Normalised Values) of Nintedanib
timeFrame: Day1, Day15 and Day 16
measure: 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)
timeFrame: Day1, Day15 and Day 16
measure: 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)
timeFrame: Day1, Day15 and Day 16
measure: Cmax,ss,Norm (Maximum Concentration of the Nintedanib in Plasma at Steady State, Normalised Values)
timeFrame: Day1, Day15 and Day 16
measure: Cmax,ss,Norm (Maximum Concentration of the BIBF 1202 in Plasma at Steady State, Normalised Values)
timeFrame: Day1, Day15 and Day 16
measure: Cmax,ss,Norm (Maximum Concentration of the BIBF 1202 Glucuronide in Plasma at Steady State, Normalised Values)
timeFrame: Day1, Day15 and Day 16
measure: fe0-12,ss (Fraction Excreted in Urine Between 0 and 12 Hours at Steady State) for Nintedanib
timeFrame: 0 to 4 hours (h), 4 to 12 h, and 12 to 24 h after nintedanib
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: 1199.39.82001 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 1199.39.82002 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 1199.39.82003 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 1199.39.82004 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 1199.39.82005 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 1199.39.82006 Boehringer Ingelheim Investigational Site
city: Changhua
country: Taiwan
facility: 1199.39.88606 Boehringer Ingelheim Investigational Site
city: Kaohsiung
country: Taiwan
facility: 1199.39.88609 Boehringer Ingelheim Investigational Site
city: Kaohsiung
country: Taiwan
facility: 1199.39.88610 Boehringer Ingelheim Investigational Site
city: Taichung
country: Taiwan
facility: 1199.39.88605 Boehringer Ingelheim Investigational Site
city: Tainan City
country: Taiwan
facility: 1199.39.88608 Boehringer Ingelheim Investigational Site
city: Tainan
country: Taiwan
facility: 1199.39.88602 Boehringer Ingelheim Investigational Site
city: Taipei
country: Taiwan
facility: 1199.39.88601 Boehringer Ingelheim Investigational Site
city: Taipei
country: Taiwan
facility: 1199.39.88603 Boehringer Ingelheim Investigational Site
city: Taoyuan County
country: Taiwan
facility: 1199.39.88604 Boehringer Ingelheim Investigational Site
city: Yunlin County
country: Taiwan
facility: 1199.39.88607 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: