Carcinoma, HepatocellularPhase 1NCT01594125
Dose Escalation Study of Nintedanib (BIBF 1120) in Japanese Patients With Hepatocellular Carcinoma
A Phase 1 study testing Nintedanib high dose, Nintedanib low dose and Nintedanib medium dose in people with Carcinoma, Hepatocellular, run by Boehringer Ingelheim at 5 sites in Japan.
Trial summary
The aim of the study is to investigate the safety, tolerability, efficacy and pharmacokinetics (PK) for Japanese hepatocellular carcinoma which are not amenable to curative surgery or loco regional therapy Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Carcinoma, Hepatocellular
- What is being tested?
- Nintedanib high dose, Nintedanib low dose and Nintedanib medium dose
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 5 sitesJapan
- Study dates
- May 2012to Jan 2015
- Phase
- Phase 1
- 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 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically/cytologically confirmed hepatocellular carcinoma not amenable to curative surgery or loco-regional therapy
- Age 20 years or older
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1
- Child-Pugh score of 7 or less
- Life expectancy more than 3 months
- Time interval from last loco-regional therapy more than 4 weeks
- Written informed consent in accordance with good clinical practice (GCP)
Who cannot join
- More than one line of prior systemic therapy for metastatic/unresectable hepatocellular carcinoma (HCC)
- Fibrolamellar HCC
- Uncontrolled or refractory ascites
- Inadequate organ function
- Variceal bleeding within 6 months or the presence of inappropriate varices
- History of major thrombotic (except portal vein thrombosis) or clinically relevant major bleeding event in the past 6 months
Show all 9Show fewer
- Major surgery within 4 weeks
- Known inherited predisposition to bleeding or thrombosis
- Significant cardiovascular diseases
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Japan5 sites
1199.120.001 Boehringer Ingelheim Investigational Site
Chuo-ku, Tokyo
1199.120.005 Boehringer Ingelheim Investigational Site
Fukuoka, Fukuoka
1199.120.002 Boehringer Ingelheim Investigational Site
Kashiwa, Chiba
1199.120.003 Boehringer Ingelheim Investigational Site
Nagoya, Aichi
1199.120.004 Boehringer Ingelheim Investigational Site
Saga, Saga
About this study
Official title: An Open Label, Dose Escalation Phase I Study to Evaluate the Safety and Tolerability of Continuous Twice-daily Oral Treatment of Nintedanib in Japanese Patients With Hepatocellular Carcinoma.
The aim of the study is to investigate the safety, tolerability, efficacy and pharmacokinetics (PK) for Japanese hepatocellular carcinoma which are not amenable to curative surgery or loco regional therapy
- Conditions
- Carcinoma, Hepatocellular
- Being tested
- Nintedanib high dose, Nintedanib low dose, Nintedanib medium dose
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nintedanib high doseDrug
twice daily oral dosing
Nintedanib low doseDrug
twice daily oral dosing
Nintedanib medium doseDrug
twice daily oral dosing
Nintedanib medium doseDrug
twice daily oral dosing
Nintedanib high doseDrug
twice daily oral dosing
| Study group | Role | What they receive |
|---|---|---|
| Group I | Experimental | patients with mild liver dysfunction according to their AST/ALT values and Child-Pugh score Receives: Drug: Nintedanib high dose; Drug: Nintedanib medium dose |
| Group II | Experimental | patients with moderate liver dysfunction according to their AST/ALT values and Child-Pugh score Receives: Drug: Nintedanib low dose; Drug: Nintedanib medium dose; Drug: Nintedanib high dose |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Dose Limiting Toxicities to Determine Maximum Tolerated Dose (MTD) of Nintedanib
The MTD is based on the incidence of Dose Limiting Toxicities (DLTs). A drug-related AE was considered as a DLT if one of the following met: CTCAE grade 4 thrombocytopenia of any duration, CTCAE grade 4 neutropenia lasting for ≥8 days, CTCAE grade 4 febrile neutropenia of any duration, CTCAE grade 3 or 4 non-haematologic toxicity (with the following exception: Alopecia, Vomiting, nausea, or diarrhoea with no adequate supportive care, Transient electrolyte abnormality, which resolves spontaneously or can be corrected with appropriate treatment within 3 days, Liver toxicity), Liver enzyme toxicity of AST, ALT, alkaline phosphatase [ALP] elevation >5x ULN, or total bilirubin >3x ULN if baseline liver enzymes are within the normal range, or AST, ALT or ALP > baseline value + 4x ULN if the baseline value is elevated. The MTD was determined to be 200mg bid.
Measured: up to 28 days
Secondary outcomes (4)
Number of Participants With Objective Tumour Response According to Response Evaluation Criteria in Solid Tumors (RECIST) 1.0
Objective response (Complete response (CR) + Partial response (PR), regardless of confirmation) is derived from a patient's best objective response by RECIST. Best objective response is calculated based on the "overall" visit response from each assessment. Best objective response represents the best response a patient has had during their time in the study up until progression, last evaluable assessment in the absence of progression or the start of subsequent anti-cancer therapy. For patients whose progression event is death, best objective response will be calculated based on data up until the last evaluable RECIST assessment prior to death.
Measured: up to 28 months
Progression Free Survival (PFS)
PFS is defined as the duration from start date of the study treatment to PD according to RECIST 1.0, or any death whichever occurs earlier.
Measured: up to 28 months
Time to Progression (TTP)
TTP is defined as the duration from the start date of the study treatment to PD according to RECIST 1.0.
Measured: up to 28 months
Number of Participants With Response by Alpha Fetoprotein (AFP)
Response by AFP is defined as 20% or more decline in AFP between the baseline value and the AFP value after three courses (12 weeks) of therapy. If patients only receive two courses of therapy the AFP value after two courses (8 weeks) will be used for the analysis.
Measured: up to 28 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2012 (estimated)
- Study startMay 2012
- Primary completionNov 2014
- Study completionJan 2015
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.
- Publications (1)Papers the sponsor has linked to this study.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 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
- NCT01594125
- Sponsor's protocol ID
- 1199.120
- Status last verified
- Jan 2016
- First submitted
- 2 May 2012
- Last updated
- 12 Feb 2016
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Okusaka T, Otsuka T, Ueno H, Mitsunaga S, Sugimoto R, Muro K, Saito I, Tadayasu Y, Inoue K, Loembe AB, Ikeda M. Phase I study of nintedanib in Japanese patients with advanced hepatocellular carcinoma and liver impairment. Cancer Sci. 2016 Dec;107(12):1791-1799. doi: 10.1111/cas.13077. Epub 2016 Dec 12.
PubMed 27627050
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label, Dose Escalation Phase I Study to Evaluate the Safety and Tolerability of Continuous Twice-daily Oral Treatment of Nintedanib in Japanese Patients With Hepatocellular Carcinoma.
- ClinicalTrials.gov ID
- NCT01594125
- Acronym / sponsor ID
- 1199.120
- Conditions
- Carcinoma, Hepatocellular
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- May 2012
- Primary completion
- Nov 2014 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 8 May 2012 (estimated)
- Results
- Posted 22 Dec 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of the study is to investigate the safety, tolerability, efficacy and pharmacokinetics (PK) for Japanese hepatocellular carcinoma which are not amenable to curative surgery or loco regional therapy
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group I | Experimental | Drug: Nintedanib high dose, Drug: Nintedanib medium dosepatients with mild liver dysfunction according to their AST/ALT values and Child-Pugh score |
| Group II | Experimental | Drug: Nintedanib low dose, Drug: Nintedanib medium dose, Drug: Nintedanib high dosepatients with moderate liver dysfunction according to their AST/ALT values and Child-Pugh score |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Histologically/cytologically confirmed hepatocellular carcinoma not amenable to curative surgery or loco-regional therapy
- Age 20 years or older
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1
- Child-Pugh score of 7 or less
- Life expectancy more than 3 months
Key exclusion criteria (9 listed)
- More than one line of prior systemic therapy for metastatic/unresectable hepatocellular carcinoma (HCC)
- Fibrolamellar HCC
- Uncontrolled or refractory ascites
- Inadequate organ function
- Variceal bleeding within 6 months or the presence of inappropriate varices
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 |
|---|---|---|
| Nintedanib high dosetwice daily oral dosing | Drug | Group I |
| Nintedanib low dosetwice daily oral dosing | Drug | Group II |
| Nintedanib medium dosetwice daily oral dosing | Drug | Group I |
| Nintedanib medium dosetwice daily oral dosing | Drug | Group II |
| Nintedanib high dosetwice daily oral dosing | Drug | Group II |
Primary outcome
Number of Participants With Dose Limiting Toxicities to Determine Maximum Tolerated Dose (MTD) of Nintedanib
Time frame: up to 28 days
The MTD is based on the incidence of Dose Limiting Toxicities (DLTs). A drug-related AE was considered as a DLT if one of the following met: CTCAE grade 4 thrombocytopenia of any duration, CTCAE grade 4 neutropenia lasting for ≥8 days, CTCAE grade 4 febrile neutropenia of any duration, CTCAE grade 3 or 4 non-haematologic toxicity (with the following exception: Alopecia, Vomiting, nausea, or diarrhoea with no adequate supportive care, Transient electrolyte abnormality, which resolves spontaneously or can be corrected with appropriate treatment within 3 days, Liver toxicity), Liver enzyme toxicity of AST, ALT, alkaline phosphatase [ALP] elevation >5x ULN, or total bilirubin >3x ULN if baseline liver enzymes are within the normal range, or AST, ALT or ALP > baseline value + 4x ULN if the baseline value is elevated. The MTD was determined to be 200mg bid.
4 secondary outcomes
Number of Participants With Objective Tumour Response According to Response Evaluation Criteria in Solid Tumors (RECIST) 1.0
Time frame: up to 28 months
Progression Free Survival (PFS)
Time frame: up to 28 months
Time to Progression (TTP)
Time frame: up to 28 months
Number of Participants With Response by Alpha Fetoprotein (AFP)
Time frame: up to 28 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27627050Okusaka T, Otsuka T, Ueno H, Mitsunaga S, Sugimoto R, Muro K, Saito I, Tadayasu Y, Inoue K, Loembe AB, Ikeda M. Phase I study of nintedanib in Japanese patients with advanced hepatocellular carcinoma and liver impairment. Cancer Sci. 2016 Dec;107(12):1791-1799. doi: 10.1111/cas.13077. Epub 2016 Dec 12.
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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
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Nintedanib high dose, Nintedanib low dose and Nintedanib medium dose in people with Carcinoma, Hepatocellular, run by Boehringer Ingelheim at 5 sites in Japan.
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 7 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 12 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Japan. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 22 Dec 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?
Number of Participants With Dose Limiting Toxicities to Determine Maximum Tolerated Dose (MTD) of Nintedanib (time frame: up to 28 days). 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 NCT01594125, which also lists 1 linked publication.
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 12 Feb 2016.