Carcinoma, HepatocellularPhase 2NCT01004003

Phase I/II Comparison of Efficacy and Safety of BIBF 1120 and Sorafenib in Patients With Advanced Hepatocellular Carcinoma

A Phase 2 study testing Sorafenib and BIBF 1120 in people with Carcinoma, Hepatocellular, run by Boehringer Ingelheim at 28 sites in 8 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The study aim is to determine maximally tolerated dose (MTD) of BIBF 1120 in HCC (hepatocellular cancer) and compare efficacy of BIBF 1120 to Sorafenib in HCC 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: 125 participants
Where: 28 sitesin 8 countries
Study dates: 22 Oct 2009to 12 Oct 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

Histologically or cytologically confirmed diagnosis of hepatocellular carcinoma (HCC) not amenable to curative surgery or loco-regional therapy (RFA, percutaneous ethanol injection (PEI), TACE)
Age 18 years or older
Eastern Cooperative Oncology Group performance score of 2 or less
Child-Pugh score A (score 5-6)
At least one measurable lesion according to RECIST 1.0 (this criterion is limited to phase II only)
In case a measurable lesion was previously treated by loco-regional therapy (RFA, PEI, TACE or RT) , this lesion must have to be documented as progression according to RECIST 1.0 by CT or MRI (this criterion is limited to phase II only).
Time interval from last local therapy (e.g. radiofrequency ablation, percutaneous ethanol injection, radiotherapy, transarterial chemoembolization) more than 4 weeks prior to start of study treatment
Written informed consent consistent with International Conference on Harmonisation/ Good Clinical Practice (ICH-GCP) and local legislation

Who cannot join

Prior systemic therapy for HCC
Fibrolamellar hepatocellular carcinoma (HCC)
Bilirubin greater than 1.5 times ULN
AST or ALT greater than 2 times ULN
Uncontrolled or refractory ascites to adequate medical therapy
Hepatic encephalopathy more than grade 1 according to Child-Pugh criteria

Show all 25Show fewer

Prothrombin time international normalized ratio greater than 2.3, or prothrombin time more than 6 seconds prolonged than control
Absolute neutrophil count less than 1000 /µL
Platelet count less than 60000 /µL
Hemoglobin less than 9 g/dL
Serum creatinine greater than 1.5 times Upper Limit of Normal (ULN)
Proteinuria of Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or greater
Variceal bleeding within last 6 months prior to start of study treatment
History of major thrombotic (except portal vein thrombosis) or clinically relevant major bleeding event in the past 6 months
Known inherited predisposition to bleeding or thrombosis
Significant cardiovascular diseases (i.e. hypertension not controlled by medical therapy, blood pressure > 150/90 mmHg), unstable angina, history of myocardial infarction within the past 6 months, congestive heart failure > class II according to New York Heart Association (NYHA), serious cardiac arrhythmia, pericardial effusion)
Therapeutic anticoagulation (except low dose heparin and/or heparin flush as needed for maintenance of an indwelling intravenous device) or antiplatelet therapy (except for chronic low-dose therapy with acetylsalicylic acid =< 325mg per day)
Major surgery within 4 weeks prior to start of study treatment
Treatment with other investigational drugs or participation in another clinical trial within the past four weeks before start of therapy or concomitantly with this trial (except for present trial drug)
Known serious illness or concomitant non-oncological disease such as neurologic, psychiatric, infectious disease or active ulcers (gastro-intestinal tract, skin) or laboratory abnormality that may increase the risk associated with study participation or study drug administration and in the judgment of the investigator would make the patient inappropriate for entry into the study
Patients who are sexually active and unwilling to use a medically acceptable method of contraception (e.g. such as implants, injectables, combined oral contraceptives, some intrauterine devices or vasectomized partner for participating females, condoms for participating males) during the trial and for at least twelve months after end of active therapy
Current alcohol abuse or drug abuse that would limit pt ability to comply with protocol
Symptomatic central nervous system (CNS) metastasis
Life expectancy less than 12 weeks
Patient unable to take oral medication

Trial locations and contacts

28 sites in 8 countries.

Country

City, postcode or hospital

28 sites in 8 countries

Germany9 sites

1199.37.49008 Boehringer Ingelheim Investigational Site
Berlin
1199.37.49009 Boehringer Ingelheim Investigational Site
Erlangen
1199.37.49002 Boehringer Ingelheim Investigational Site
Freiburg im Breisgau
1199.37.49001 Boehringer Ingelheim Investigational Site
Hanover
1199.37.49010 Boehringer Ingelheim Investigational Site
Heidelberg
1199.37.49005 Boehringer Ingelheim Investigational Site
Jena
1199.37.49004 Boehringer Ingelheim Investigational Site
Magdeburg
1199.37.49003 Boehringer Ingelheim Investigational Site
München
1199.37.49006 Boehringer Ingelheim Investigational Site
Tübingen

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United Kingdom7 sites

1199.37.44001 Boehringer Ingelheim Investigational Site
Edgbaston, Birmingham
1199.37.44005 Boehringer Ingelheim Investigational Site
Glasgow
1199.37.44008 Boehringer Ingelheim Investigational Site
Liverpool
1199.37.44002 Boehringer Ingelheim Investigational Site
London
1199.37.44003 Boehringer Ingelheim Investigational Site
London
1199.37.44006 Boehringer Ingelheim Investigational Site
Manchester
1199.37.44004 Boehringer Ingelheim Investigational Site
Nottingham

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Poland3 sites

1199.37.48002 Boehringer Ingelheim Investigational Site
Olsztyn
1199.37.48001 Boehringer Ingelheim Investigational Site
Warsaw
1199.37.48003 Boehringer Ingelheim Investigational Site
Warsaw

Other trials in Poland

Austria2 sites

1199.37.43001 Boehringer Ingelheim Investigational Site
Vienna
1199.37.43002 Boehringer Ingelheim Investigational Site
Vienna

Other trials in Austria

France2 sites

1199.37.33001 Boehringer Ingelheim Investigational Site
Paris
1199.37.33002 Boehringer Ingelheim Investigational Site
Paris

Other trials in France

Netherlands2 sites

1199.37.31002 Boehringer Ingelheim Investigational Site
Leiden
1199.37.31001 Boehringer Ingelheim Investigational Site
Utrecht

Other trials in Netherlands

Romania2 sites

1199.37.40002 Boehringer Ingelheim Investigational Site
Bucharest
1199.37.40003 Boehringer Ingelheim Investigational Site
Cluj-Napoca

Other trials in Romania

Hungary1 site

1199.37.36001 Boehringer Ingelheim Investigational Site
Debrecen

Other trials in Hungary

About this study

Official title: A Multicenter, Open Label, Phase I /Randomised Phase II Study to Evaluate Safety, Pharmacokinetics and Efficacy of BIBF 1120 in Comparison With Oral Sorafenib for Advanced Hepatocellular Carcinoma Patients.

The study aim is to determine maximally tolerated dose (MTD) of BIBF 1120 in HCC (hepatocellular cancer) and compare efficacy of BIBF 1120 to Sorafenib in HCC 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
BIBF 1120Drug
Dose escalated in phase I until MTD or adjusted by investigator, dose in phase II part based on phase I data

Study groups in NCT01004003
Study group	Role	What they receive
BIBF 1120	Experimental	Phase I dose escalation and phase II using dose determined in phase I ( 200 mg BID) Receives: Drug: BIBF 1120
Sorafenib	Active comparator	Not described 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 dose limiting toxicities (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 (15 July 2014); Up to 1031 days

Secondary outcomes (4)

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 (15 July 2014); Up to 1031 days
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 (15 July 2014); Up to 1031 days
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 (15 July 2014); Up to 1031 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

22 Oct 200912 Oct 2016

First posted29 Oct 2009 (estimated)
Study start22 Oct 2009
Primary completion14 Jul 2014
Study completion12 Oct 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: 125 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01004003
Sponsor's protocol ID: 1199.37
Other IDs: 2009-011925-14, 2009
Status last verified: Sep 2017
First submitted: 12 Oct 2009
Last updated: 26 Oct 2017
Results posted: Yes, on ClinicalTrials.gov

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 26 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multicenter, Open Label, Phase I /Randomised Phase II Study to Evaluate Safety, Pharmacokinetics and Efficacy of BIBF 1120 in Comparison With Oral Sorafenib for Advanced Hepatocellular Carcinoma Patients.
ClinicalTrials.gov ID: NCT01004003
Acronym / sponsor ID: 1199.37
Conditions: Carcinoma, Hepatocellular
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 125 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Study start: 22 Oct 2009 (actual)
Primary completion: 14 Jul 2014 (actual)
Study completion: 12 Oct 2016 (actual)
First posted: 29 Oct 2009 (estimated)
Results: Posted 7 Aug 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The study aim is to determine maximally tolerated dose (MTD) of BIBF 1120 in HCC (hepatocellular cancer) and compare efficacy of BIBF 1120 to Sorafenib in HCC patients

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
BIBF 1120	Experimental	Drug: BIBF 1120Phase I dose escalation and phase II using dose determined in phase I ( 200 mg BID)
Sorafenib	Active comparator	Drug: Sorafenib

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

Histologically or cytologically confirmed diagnosis of hepatocellular carcinoma (HCC) not amenable to curative surgery or loco-regional therapy (RFA, percutaneous ethanol injection (PEI), TACE)
Age 18 years or older
Eastern Cooperative Oncology Group performance score of 2 or less
Child-Pugh score A (score 5-6)
At least one measurable lesion according to RECIST 1.0 (this criterion is limited to phase II only)

Key exclusion criteria (25 listed)

Prior systemic therapy for HCC
Fibrolamellar hepatocellular carcinoma (HCC)
Bilirubin greater than 1.5 times ULN
AST or ALT greater than 2 times ULN
Uncontrolled or refractory ascites to adequate medical therapy

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
Sorafenib	Drug	Sorafenib
BIBF 1120Dose escalated in phase I until MTD or adjusted by investigator, dose in phase II part based on phase I data	Drug	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 dose limiting toxicities (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 (15 July 2014); Up to 1031 days
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.

4 secondary outcomes

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 (15 July 2014); Up to 1031 days
Progression Free Survival (PFS)
Time frame: From randomization until data cut-off (15 July 2014); Up to 1031 days
Overall Survival
Time frame: From randomization until data cut-off (15 July 2014); Up to 1031 days

Results and safety

Results posted to the registry on 7 Aug 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Phase 1 Group 1, 100mg Nintedanib Bid	6	0
Phase I Group 1, 150mg Nintedanib Bid	3	0
Phase I Group 1, 200mg Nintedanib Bid	4	0
Phase I Group 2, 50mg Nintedanib Bid	3	0
Phase I Group 2, 100mg Nintedanib Bid	4	0
Phase I Group 2, 150mg Nintedanib Bid	4	0
Phase I Group 2, 200mg Nintedanib Bid	8	0
Phase II, 200 mg Nintedanib Bid	62	2
Phase II, 400 mg Sorafenib Bid	31	1

Primary outcome: Maximum Tolerated Dose in Phase I

Time frame: 4 weeks. Number. Unit: mg bid

Measure	Group 1 n = 9	Group 2 n = 13
Value	200	200

Population analysed: Treated set which included all patients who received at least one single dose of trial medication, including phase I patients from the dose escalation part that were not replaced for MTD determination.

Primary outcome: Time to Progression (TTP) in Phase II

Time frame: From randomization until data cut-off (15 July 2014); Up to 1031 days. Median (Inter-Quartile Range). Unit: months

Measure	Phase II, 200 mg Nintedanib Bid n = 62	Phase II, 400 mg Sorafenib Bid n = 31
Value	5.45 (2.69 to 9.20)	4.63 (2.79 to 20.40)

Phase II, 200 mg Nintedanib Bid vs Phase II, 400 mg Sorafenib Bid: Hazard Ratio (HR): 1.437 (95% CI 0.805 to 2.565)

Population analysed: Treated set, only phase II participants.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: From first administration of the trial drug and until 28 days after the last administration of nintedanib or sorafenib, up to 1289 days. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Phase 1 Group 1, 100mg Nintedanib Bid	3 of 6 (50%)	6 of 6 (100%)	Not reported
Phase I Group 1, 150mg Nintedanib Bid	1 of 3 (33.3%)	3 of 3 (100%)	Not reported
Phase I Group 1, 200mg Nintedanib Bid	4 of 4 (100%)	4 of 4 (100%)	Not reported
Phase I Group 2, 50mg Nintedanib Bid	3 of 3 (100%)	3 of 3 (100%)	Not reported
Phase I Group 2, 100mg Nintedanib Bid	2 of 4 (50%)	4 of 4 (100%)	Not reported
Phase I Group 2, 150mg Nintedanib Bid	3 of 4 (75%)	4 of 4 (100%)	Not reported
Phase I Group 2, 200mg Nintedanib Bid	4 of 8 (50%)	7 of 8 (87.5%)	Not reported
Phase II, 200 mg Nintedanib Bid	34 of 62 (54.8%)	61 of 62 (98.4%)	Not reported
Phase II, 400 mg Sorafenib Bid	14 of 31 (45.2%)	31 of 31 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2017.
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

28 sites in 8 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 28 sites in 8 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 8 inclusion and 25 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 26 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 28 sites in Germany, United Kingdom, Poland, Austria, France and 3 more countries. 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 7 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?

On the ClinicalTrials.gov record for NCT01004003.

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 26 Oct 2017.