Hepatocellular Carcinoma (HCC)ACTESNCT02834546
Correlation Between Sorafenib Plasma Concentrations, Toxicity and Disease Control Rate in Patients Treated by Sorafenib for Hepatocellular Carcinoma
An observational study of Hepatocellular Carcinoma (HCC), run by University Hospital, Bordeaux at 5 sites in France.
Trial summary
The aim of this pilot study is to correlate the sorafenib plasma concentration to observed toxicity and to the disease control rate in 100 patients undergoing a palliative treatment of hepatocellular carcinoma (HCC). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma (HCC)
- What is being tested?
- Sorafenib plasma concentration 4 weeks after treatment initiation
- How many people
- 143 participants
- Where
- 5 sitesFrance
- Study dates
- 25 Jul 2017to 15 Mar 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
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
Study population: Patient with HCC from 5 care centers in France for whom the indication of a first treatment with sorafenib was decided and who will be treated according to the recommendations of drug SmpC
Who may be able to join
- Subjects > 18 years age
- Possibility of regular monitoring
- Ability to understand and willingness to sign written informed consent.
- Hepatocellular carcinoma histologically diagnosed or in case of inability to perform a histology by non-invasive radiological criteria endorsed by EASL/AASLD (a) presence of known cirrhosis and (b) identification of a focal hepatic lesion measuring at least 1cm in diameter with contrast uptake in the arterial phase and rapid wash out in the venous /late phase on two imaging techniques
- Patient not eligible for curative treatment (transplantation, resection, destruction or percutaneous chemo-embolization) or HCC still evolving after failure of a specific treatment
- ECOG ≤ 2
- Child-Pugh A or B
- Score BCLC B or C
Who cannot join
- Any condition that is unstable or could jeopardize the safety of the subject and their compliance in the study
- Cirrhosis CHILD C
- Score BCLC D
- ECOG > 2
- Digestive bleeding within 30 days before inclusion
- Subject has had a liver transplant or waiting for a liver transplant
- Subject previously treated with sorafenib
- Childbearing or breastfeeding women
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
France5 sites
Institut Bergonié
Bordeaux
CHU de Limoges
Limoges
CHU de Montpellier
Montpellier
CHU de Bordeaux
Pessac
CHU de Toulouse
Toulouse
About this study
The aim of this pilot study is to correlate the sorafenib plasma concentration to observed toxicity and to the disease control rate in 100 patients undergoing a palliative treatment of hepatocellular carcinoma (HCC). If some correlations are observed, we will consider planning a larger interventional study to adjust sorafenib daily dose to plasma concentration.
Read the detailed description
Sorafenib is the standard of care for the palliative treatment of HCC. The recommended dose of sorafenib in patients with HCC is 400 mg twice daily. Sorafenib dose-limiting toxicities include diarrhea, arterial hypertension and hand-foot syndrome. Owing a large inter-patient variability (near 50%) of sorafenib Area Under the Curve (AUC) over 12h, an over-exposure to sorafenib could explain acute toxicity. On the other hand, a suboptimal exposure could result in an insufficient anti-tumor activity as suggested by a recent study. This inter-patient variability of sorafenib pharmacokinetic is especially relevant in HCC. Indeed, most of HCC are developed on cirrhotic liver with often an impaired liver function, a decrease of albuminemia and sometimes ascitis. All these parameters are likely to impact the sorafenib pharmacokinetic. The aim of this pilot study is to correlate the sorafenib plasma concentration to observed toxicity and to the disease control rate in 100 patients.
The dose of sorafenib will be the recommended dose: 400 mg twice daily. Sorafenib daily doses will be only adjusted by the clinician on adverse event. Values of sorafenib AUC will not be transmitted to clinician.
Patients will be followed during 12 months with 5 visits: Week 4, Week 8, Week 16, Month 6 and Month 12. Adverse event related to sorafenib will be recorded and graded according to the NCI-CTC for Adverse Event during all the study period. Sorafenib plasma concentrations will be assessed at 4, 8 and 16 weeks. An additional dosage could be performed between W1 and W4, before dose modification, if a dose modification is necessary due to adverse events before W4.
- Conditions
- Hepatocellular Carcinoma (HCC)
- Being tested
- Sorafenib plasma concentration 4 weeks after treatment initiation
- Keywords
- Hepatocellular Carcinoma, Sorafenib, Toxicity, Plasmatic concentration
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sorafenib plasma concentration 4 weeks after treatment initiationBiological
Sorafenib plasma concentrations will be assessed at 4, 8 and 16 weeks by high performance liquid chromatography. The pharmacology Unit of Bordeaux university hospital (Pr Molimard) is a French Center of reference for the dosage of TKI in the plasma
| Study group | Role | What they receive |
|---|---|---|
| Patients with HCC treated with sorafenib | Not described Receives: Biological: Sorafenib plasma concentration 4 weeks after treatment initiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse events related to Sorafenib needing a dose adjustment or a symptomatic medication
Measured: Up 8 weeks after sorafenib treatment introduction
Secondary outcomes (4)
Adverse events notification
Measured: Week 8, 16, month 6 and 12 after sorafenib treatment introduction
Radiological response assessed by scan or MRI
Measured: Week 8, 16, month 6 and 12 after sorafenib treatment introduction
Progression-free survival time
Measured: Up to month 12 after sorafenib treatment introduction
Overall survival
Measured: Up to month 12 after sorafenib treatment introduction
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jul 2016 (estimated)
- Study start25 Jul 2017
- Primary completion15 Mar 2019
- Study completion15 Mar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular Carcinoma (HCC)Studies of the same condition, open and under way.
- More trials run by University Hospital, BordeauxThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 143 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Bordeaux
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Eric FRISON, MD, Study chair, Unité de Soutien Méthodologique à la Recherche clinique et épidémiologique du CHU de Bordeaux
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02834546
- Sponsor's protocol ID
- CHUBX 2014/25
- Acronym
- ACTES
- Status last verified
- Apr 2020
- First submitted
- 13 Jul 2016
- Last updated
- 29 Apr 2020
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Correlation Between Sorafenib Plasma Concentrations, Toxicity and Disease Control Rate in Patients Treated by Sorafenib for Hepatocellular Carcinoma
- ClinicalTrials.gov ID
- NCT02834546
- Acronym / sponsor ID
- ACTES / CHUBX 2014/25
- Conditions
- Hepatocellular Carcinoma (HCC)
- Keywords
- Hepatocellular Carcinoma, Sorafenib, Toxicity, Plasmatic concentration
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 143 participants (actual)
- Lead sponsor
- University Hospital, BordeauxUniversity, hospital or other
- Study start
- 25 Jul 2017 (actual)
- Primary completion
- 15 Mar 2019 (actual)
- Study completion
- 15 Mar 2019 (actual)
- First posted
- 15 Jul 2016 (estimated)
- Results
- Not posted in the source record
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 this pilot study is to correlate the sorafenib plasma concentration to observed toxicity and to the disease control rate in 100 patients undergoing a palliative treatment of hepatocellular carcinoma (HCC). If some correlations are observed, we will consider planning a larger interventional study to adjust sorafenib daily dose to plasma concentration.
Detailed description
Sorafenib is the standard of care for the palliative treatment of HCC. The recommended dose of sorafenib in patients with HCC is 400 mg twice daily. Sorafenib dose-limiting toxicities include diarrhea, arterial hypertension and hand-foot syndrome. Owing a large inter-patient variability (near 50%) of sorafenib Area Under the Curve (AUC) over 12h, an over-exposure to sorafenib could explain acute toxicity. On the other hand, a suboptimal exposure could result in an insufficient anti-tumor activity as suggested by a recent study. This inter-patient variability of sorafenib pharmacokinetic is especially relevant in HCC. Indeed, most of HCC are developed on cirrhotic liver with often an impaired liver function, a decrease of albuminemia and sometimes ascitis. All these parameters are likely to impact the sorafenib pharmacokinetic. The aim of this pilot study is to correlate the sorafenib plasma concentration to observed toxicity and to the disease control rate in 100 patients.
The dose of sorafenib will be the recommended dose: 400 mg twice daily. Sorafenib daily doses will be only adjusted by the clinician on adverse event. Values of sorafenib AUC will not be transmitted to clinician.
Patients will be followed during 12 months with 5 visits: Week 4, Week 8, Week 16, Month 6 and Month 12. Adverse event related to sorafenib will be recorded and graded according to the NCI-CTC for Adverse Event during all the study period. Sorafenib plasma concentrations will be assessed at 4, 8 and 16 weeks. An additional dosage could be performed between W1 and W4, before dose modification, if a dose modification is necessary due to adverse events before W4.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients with HCC treated with sorafenib | – | Biological: Sorafenib plasma concentration 4 weeks after treatment initiation |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patient with HCC from 5 care centers in France for whom the indication of a first treatment with sorafenib was decided and who will be treated according to the recommendations of drug SmpC
Key inclusion criteria (8 listed)
- Subjects > 18 years age
- Possibility of regular monitoring
- Ability to understand and willingness to sign written informed consent.
- Hepatocellular carcinoma histologically diagnosed or in case of inability to perform a histology by non-invasive radiological criteria endorsed by EASL/AASLD (a) presence of known cirrhosis and (b) identification of a focal hepatic lesion measuring at least 1cm in diameter with contrast uptake in the arterial phase and rapid wash out in the venous /late phase on two imaging techniques
- Patient not eligible for curative treatment (transplantation, resection, destruction or percutaneous chemo-embolization) or HCC still evolving after failure of a specific treatment
Key exclusion criteria (8 listed)
- Any condition that is unstable or could jeopardize the safety of the subject and their compliance in the study
- Cirrhosis CHILD C
- Score BCLC D
- ECOG > 2
- Digestive bleeding within 30 days before inclusion
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 plasma concentration 4 weeks after treatment initiationSorafenib plasma concentrations will be assessed at 4, 8 and 16 weeks by high performance liquid chromatography. The pharmacology Unit of Bordeaux university hospital (Pr Molimard) is a French Center of reference for the dosage of TKI in the plasma | Biological | Patients with HCC treated with sorafenib |
Primary outcome
Adverse events related to Sorafenib needing a dose adjustment or a symptomatic medication
Time frame: Up 8 weeks after sorafenib treatment introduction
4 secondary outcomes
Adverse events notification
Time frame: Week 8, 16, month 6 and 12 after sorafenib treatment introduction
Radiological response assessed by scan or MRI
Time frame: Week 8, 16, month 6 and 12 after sorafenib treatment introduction
Progression-free survival time
Time frame: Up to month 12 after sorafenib treatment introduction
Overall survival
Time frame: Up to month 12 after sorafenib treatment introduction
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Apr 2020.
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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.
Eric FRISON, MD study chair
Unité de Soutien Méthodologique à la Recherche clinique et épidémiologique du CHU de Bordeaux
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hepatocellular Carcinoma (HCC), run by University Hospital, Bordeaux at 5 sites in France.
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 8 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 29 Apr 2020. 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 France. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Adverse events related to Sorafenib needing a dose adjustment or a symptomatic medication (time frame: Up 8 weeks after sorafenib treatment introduction). 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 29 Apr 2020.