Carcinoma, HepatocellularPhase 2NCT00987935
A Phase I / II Trial of Nintedanib in Asian Hepatocellular Carcinoma Patients
A Phase 2 study testing Sorafenib and BIBF 1120 in people with Carcinoma, Hepatocellular, run by Boehringer Ingelheim at 16 sites in 2 countries.
Trial summary
This study is to evaluate the safety, appropriate dose, and efficacy of BIBF 1120 in liver cancer patients Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Hepatocellular
- What is being tested?
- Sorafenib and BIBF 1120
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 134 participants
- Where
- 16 sitesin 2 countries
- Study dates
- Oct 2009to Jan 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Hepatocellular carcinoma, either histologically/cytologically confirmed or clinically diagnosed, which is not amenable to curative surgery or loco-regional therapy
- Age 18 years or older
- Eastern Cooperative Group performance score of 2 or less
- Child-Pugh score of 7 or less
- Written informed consent in accordance with International Conference on Harmonisation (ICH) and Good Clinical Practice (GCP) and local legislation
Who cannot join
- Prior systemic therapy for metastatic/unresectable hepatocellular carcinoma (for phase II)
- More than one line of prior systemic therapy for metastatic/unresectable hepatocellular carcinoma (for phase I)
- Uncontrolled or refractory ascites to adequate medical therapy
- Bilirubin greater than 1.5 times upper limit of normal
- Aspartate amino transferase or alanine amino transferase greater than 5 times upper limit of normal
- Absolute neutrophil count less than 1500/microliter
Show all 9Show fewer
- Platelet count less than 75000/microliter
- Hemoglobin less than 9 g/dL
- Serum creatinine greater than 1.5 times upper limit of normal
Trial locations and contacts
16 sites in 2 countries.
16 sites in 2 countries
Taiwan10 sites
1199.39.88606 Boehringer Ingelheim Investigational Site
Changhua
1199.39.88609 Boehringer Ingelheim Investigational Site
Kaohsiung City
1199.39.88610 Boehringer Ingelheim Investigational Site
Kaohsiung City
1199.39.88605 Boehringer Ingelheim Investigational Site
Taichung
1199.39.88602 Boehringer Ingelheim Investigational Site
Tainan
1199.39.88608 Boehringer Ingelheim Investigational Site
Tainan
1199.39.88601 Boehringer Ingelheim Investigational Site
Taipei
1199.39.88603 Boehringer Ingelheim Investigational Site
Taipei
1199.39.88604 Boehringer Ingelheim Investigational Site
Taoyuan County
1199.39.88607 Boehringer Ingelheim Investigational Site
Yunlin County
South Korea6 sites
1199.39.82001 Boehringer Ingelheim Investigational Site
Seoul
1199.39.82002 Boehringer Ingelheim Investigational Site
Seoul
1199.39.82003 Boehringer Ingelheim Investigational Site
Seoul
1199.39.82004 Boehringer Ingelheim Investigational Site
Seoul
1199.39.82005 Boehringer Ingelheim Investigational Site
Seoul
1199.39.82006 Boehringer Ingelheim Investigational Site
Seoul
About this study
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.
This study is to evaluate the safety, appropriate dose, and efficacy of BIBF 1120 in liver cancer patients
- Conditions
- Carcinoma, Hepatocellular
- Being tested
- Sorafenib, BIBF 1120
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SorafenibDrug
400 mg twice daily
BIBF 1120Drug
Twice daily
| Study group | Role | What they receive |
|---|---|---|
| Nintedanib (BIBF 1120) | Experimental | Phase I dose escalation and phase II using dose determined in phase I Receives: Drug: BIBF 1120 |
| Sorafenib | Active comparator | Twice daily dosing in phase II Receives: Drug: Sorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose in Phase I
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.
Measured: 4 weeks
Time to Progression (TTP) in Phase II
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.
Measured: From randomization until data cut-off (28 Sep 2012); Up to 77 weeks
Secondary outcomes (13)
Time to Progression (TTP) in Phase II (Follow-up Analyses)
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.
Measured: From randomization until disease progression or data cut-off (16 Jul 2014); Up to 171 weeks
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.
Incidence and worst intensity (severity) of Adverse Events with grading according to the Common Terminology Criteria for Adverse Events (CTCAE version 3.0).
Measured: AEs with an onset during therapy with study treatment or within 28 days after discontinuation of study treatment (up to 1066 days)
Incidence of Dose Limiting Toxicity in Phase I
Number of patients with dose limiting toxicity are presented
Measured: 4 weeks
Objective Tumour Response by RECIST
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.
Measured: From randomization until data cut-off (16 July 2014); Up to 171 weeks
Progression Free Survival (PFS)
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.
Measured: From randomization until data cut-off (16 July 2014); Up to 171 weeks
Overall Survival
Overall survival was defined as the duration from date of randomisation to the date of death.
Measured: From randomization until data cut-off (16 July 2014); Up to 171 weeks
AUC0-12,ss,Norm (Area Under the Plasma Concentration-time Curve Between 0 and 12 Hours at Steady State, Normalised Values) of Nintedanib
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.
Measured: 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)
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.
Measured: 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 Glucuronide (Metabolite of Nintedanib)
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.
Measured: Day1, Day15 and Day 16
Cmax,ss,Norm (Maximum Concentration of the Nintedanib in Plasma at Steady State, Normalised Values)
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.
Measured: Day1, Day15 and Day 16
Cmax,ss,Norm (Maximum Concentration of the BIBF 1202 in Plasma at Steady State, Normalised Values)
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.
Measured: Day1, Day15 and Day 16
Cmax,ss,Norm (Maximum Concentration of the BIBF 1202 Glucuronide in Plasma at Steady State, Normalised Values)
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.
Measured: Day1, Day15 and Day 16
fe0-12,ss (Fraction Excreted in Urine Between 0 and 12 Hours at Steady State) for 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.
Measured: 0 to 4 hours (h), 4 to 12 h, and 12 to 24 h after nintedanib
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2009 (estimated)
- Study startOct 2009
- Primary completionJul 2014
- Study completionJan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Carcinoma, HepatocellularStudies of the same condition, open and under way.
- More trials run by Boehringer IngelheimThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 134 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boehringer Ingelheim
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Boehringer Ingelheim, Study chair, Boehringer Ingelheim
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00987935
- Sponsor's protocol ID
- 1199.39
- Status last verified
- Feb 2016
- First submitted
- 30 Sep 2009
- Last updated
- 10 Mar 2016
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT00987935
- Acronym / sponsor ID
- 1199.39
- Conditions
- Carcinoma, Hepatocellular
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 134 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- Oct 2009
- Primary completion
- Jul 2014 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 1 Oct 2009 (estimated)
- Results
- Posted 27 Aug 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is to evaluate the safety, appropriate dose, and efficacy of BIBF 1120 in liver cancer patients
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Nintedanib (BIBF 1120) | Experimental | Drug: BIBF 1120Phase I dose escalation and phase II using dose determined in phase I |
| Sorafenib | Active comparator | Drug: SorafenibTwice daily dosing in phase II |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Hepatocellular carcinoma, either histologically/cytologically confirmed or clinically diagnosed, which is not amenable to curative surgery or loco-regional therapy
- Age 18 years or older
- Eastern Cooperative Group performance score of 2 or less
- Child-Pugh score of 7 or less
- Written informed consent in accordance with International Conference on Harmonisation (ICH) and Good Clinical Practice (GCP) and local legislation
Key exclusion criteria (9 listed)
- Prior systemic therapy for metastatic/unresectable hepatocellular carcinoma (for phase II)
- More than one line of prior systemic therapy for metastatic/unresectable hepatocellular carcinoma (for phase I)
- Uncontrolled or refractory ascites to adequate medical therapy
- Bilirubin greater than 1.5 times upper limit of normal
- Aspartate amino transferase or alanine amino transferase greater than 5 times upper limit of normal
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sorafenib400 mg twice daily | Drug | Sorafenib |
| BIBF 1120Twice daily | Drug | Nintedanib (BIBF 1120) |
Primary outcome
Maximum Tolerated Dose in Phase I
Time frame: 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
Time frame: 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.
13 secondary outcomes
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
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)
Incidence of Dose Limiting Toxicity in Phase I
Time frame: 4 weeks
Objective Tumour Response by RECIST
Time frame: From randomization until data cut-off (16 July 2014); Up to 171 weeks
Progression Free Survival (PFS)
Time frame: From randomization until data cut-off (16 July 2014); Up to 171 weeks
Overall Survival
Time frame: From randomization until data cut-off (16 July 2014); Up to 171 weeks
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
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
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
Cmax,ss,Norm (Maximum Concentration of the Nintedanib in Plasma at Steady State, Normalised Values)
Time frame: Day1, Day15 and Day 16
Cmax,ss,Norm (Maximum Concentration of the BIBF 1202 in Plasma at Steady State, Normalised Values)
Time frame: Day1, Day15 and Day 16
Cmax,ss,Norm (Maximum Concentration of the BIBF 1202 Glucuronide in Plasma at Steady State, Normalised Values)
Time frame: Day1, Day15 and Day 16
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Boehringer Ingelheim study chair
Boehringer Ingelheim
16 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sorafenib and BIBF 1120 in people with Carcinoma, Hepatocellular, run by Boehringer Ingelheim at 16 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in Taiwan, South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Aug 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose in Phase I (time frame: 4 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2016.