Liver CancerPhase 2IDASPHERE IINCT02185768
Chemoembolisation of Hepatocellular Carcinomas Not Subject to Interventive Care by Idarubicin-loaded Beads - IDASPHERE II
A Phase 2 study testing idarubicin and Dc- Beads 300-500µm in people with Liver Cancer, run by Federation Francophone de Cancerologie Digestive at 7 sites in France.
Trial summary
The most frequently used products in CHE are doxorubicin (36%), cisplatin (31%), and epirubicin (12%). But until recently, there were no obvious reasons to use one product over another. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Cancer
- What is being tested?
- idarubicin and Dc- Beads 300-500µm
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 46 participants
- Where
- 7 sitesFrance
- Study dates
- Jan 2015to Oct 2017
- 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 diagnosed HCC or HCC diagnosed according to the EASL criteria
- Measurable targets according to the mRECIST v1.1 criterion
- Preserved liver function (in case of Child-Pugh A or B7 cirrhosis)
- Tumour not subject to interventive care (liver transplant, surgical resection or percutaneous destruction)
- BCLC A/B without portal or extra-hepatic invasion
- No prior treatment by chemotherapy, radiotherapy or transarterial embolisation (with or without chemotherapy)
Show all 10Show fewer
- Age ≥ 18 years
- WHO 0 or 1
- Laboratory test: platelets ≥ 50,000 mm3, N ≥ 1,000/mm3, creatininaemia ≤ 150 µmol/L, PT ≥ 50%
- No heart failure (isotope or ultrasound VEF > 50%)
Who cannot join
- - Advanced tumour (vascular or extra-hepatic invasion including brain metastasis or diffuse HCC with liver invasion > 50%)
- History of other type of cancer except cancer known to be in remission for more than 5 years (in this case, HCC histological proof is required), or basal-cell carcinoma or in situ cervix uteri cancer properly treated with curative treatment
- Advanced liver disease (Child B8, B9 and C, bilirubinaemia > 3 mg/dL, SGOT and SGPT > 5 x ULN or 250 U/L)
- Previous treatment by idarubicin and/or doxorubicin
- Idarubicin contraindications (cardiopathy with myocardial failure, serious kidney or liver failure, yellow fever vaccine)
- Concurrent disease or uncontrolled severe clinical condition
Show all 18Show fewer
- Uncontrolled severe infection
- Patient requiring long-term anticoagulant treatment
- Thrombosis of the portal vein or a 3-segment region or more
- Hepatofugal portal venous flow
- Presence of serious atheromatosis
- Presence of collateral vascular ways potentially affecting the normal regions during embolisation
- Presence of arthritis of the hepatic artery branches to be treated
- Presence of arterioportal or arterial subhepatic fistula that cannot be embolised by coils
- Pregnancy or breastfeeding
- Absence of effective contraception (for men and women of childbearing age)
- Patient who cannot be regularly monitored on account of psychological, social, family- or geography-related reasons
- Concomitant participation of a patient in another study
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
France7 sites
CHU Amiens
Amiens
CHU d'ANGERS
Angers, 49933
CHU - Hôpital François Mitterand
Dijon, 21079
Hôpital La Croix Rousse
Lyon, 69317
Hôpital Edouard Herriot
Lyon, 69437
CHU St Eloi
Montpellier, 34295
Hôpital de l'Archet II
Nice, 06202
About this study
The most frequently used products in CHE are doxorubicin (36%), cisplatin (31%), and epirubicin (12%). But until recently, there were no obvious reasons to use one product over another. In fact, systemic chemotherapy is considered ineffective in HCC [hepatocellular carcinoma], which does not allow any argument in favour of the product. Moreover, 2 randomised trials comparing the molecules (doxorubicin vs. epirubicin) proved to be negative in terms of survival.
Cytotoxicity of different anticancer agents on HCC cell lines have been compared in order to select the best candidate for CHE. Eleven chemotherapy molecules have been tested, including those more frequently used in CHE. Among them, idarubicin (an anthracycline) proved to be the most effective in vitro by far. The superiority of idarubicin (as opposed to doxorubicin) was noted especially on the SNU-449 line, which is known for its resistance to several chemotherapy agents. The best cytotoxicity of idarubicin can be explained by 2 mechanisms: 1) idarubicin has a better intracellular penetration than the other anthracyclines. This is probably due to its more considerable lipophily, facilitating thus its passage through the membrane made up of a double lipid layer, 2) idarubicin is resistant to the multidrug resistance system (MDR). The MDR mechanism, which is often noted in HCC, consists of membrane pumps transporting the molecule outside the cell. These two particularities could explain a more significant accumulation of idarubicin in the HCC cells, and thus better efficacy. It is interesting to note that orally administered idarubicin (5 mg/day for 21 days) has proved to be less toxic and is effective in HCC. Currently, idarubicin is used to treat leukaemia. Its toxicity profile (especially, haematological and cardiac) is known.
Read more
On these grounds, A pilot study has been conducted in order to assess the tolerance and efficacy of lipiodol-based CHE using a 10 mg dose of idarubicin in 21 patients with unresectable HCC. These preliminary data reveal that CHE with idarubicin is effective and less toxic.
Idarubicin can be loaded in microbeads. A phase I study (IDASPHERE) has been conducted on DC Beads® microbeads (300-500µm) loaded with idarubicin (dose increased from 5 to 25 mg). The DLT [dose-limiting toxicity] and MTD [maximum tolerated dose] have been determined in 21 patients using a CRM. The MTD of idarubicin was assessed at 10 mg. In our study, the idarubicin-loaded beads did not give rise to any specific toxicity-related problem. The 10 mg dose is compatible with the known toxicity profile of idarubicin: cumulative cardiotoxicity of doxorubicin is noted from 550 mg/m², whereas that of idarubicin is noted from 93 mg/m². There is thus a 5.9:1 ratio between their cumulative toxicities. The most frequently used dose (and also the weakest one) for the doxorubicin-based CHE is 50 mg. The equivalent of the idarubicin dose would thus be: 50 mg (doxorubicin) / 5.9 (doxorubicin/idarubicin ratio) = approx. 10 mg of idarubicin.
It has been already demonstrated that hepatic extraction of idarubicin is better than those of doxorubicin and daunorubicin in an animal sarcoma model. In this study, AUC 0-48h and AUC 0-72h were 1.35 times higher with idarubicin, proving that its intra-hepatic penetration was 35% higher.
The randomised phase II PRECISION V study compared conventional CHE (cCHE) with CHE by doxorubicin beads (DC Bead®) in patients with HCC. It is currently the largest randomised trial on CHE published. The PRECISION V data can be thus used to compare the other studies in terms of efficacy and tolerance.
To continue our preliminary study and the phase I IDASPHERE study, investigators wish to assess thus the efficacy and confirm the tolerance of idarubicin-loaded beads for the CHE of HCC according to a protocol similar to PRECISION V, as part of a single-arm phase II study.
Read the detailed description
By using a 2-step Fleming plan (Fleming, 1982) with a unilateral alpha risk of 5% and 90% potency, it is necessary to include 86 assessable patients.
On the 1st step: 43 patients will be included (+/- 2 patients, if non-assessable patient(s)
- If 10 patients or less present an objective response, the trial will be discontinued on grounds of futility (H1 rejected)
- If 18 patients or less present an objective response, the trial will be discontinued on grounds of efficacy (H0 rejected)
If not, we proceed with the 2nd step including 43 additional patients. If 29 patients or more present an objective response, the treatment will be considered as effective (H0 rejected)
Considering a 5% ratio of visual loss or non-assessable patients, 91 patients will be included.
- Conditions
- Liver Cancer
- Being tested
- idarubicin, Dc- Beads 300-500µm
- Keywords
- Liver cancer
- Medical subject headings
- Liver Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
idarubicinDrug
Dc- Beads 300-500µmDevice
| Study group | Role | What they receive |
|---|---|---|
| DC-BEADS + Idarubicin | Experimental | Chemoembolization with DC BEAD loaded with idarubicin Receives: Drug: idarubicin; Device: Dc- Beads 300-500µm |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Complete Response or Partial Response (Objective Response), as Assessed According Central Review
The main judgement criterion is the rate of patients in objective response (complete or partial response) at 6 months according to the mRECIST criteria and based on the central review. Response Evaluation Criteria In Solid Tumors Criteria (mRECIST v1.0) for target lesions was assessed by MRI Complete Response (CR) was defined as : Disappearance of all target lesions and Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Objective Response was defind as the number of patients with a CR or a PR.
Measured: up to 6 months
Secondary outcomes (4)
Number of Participants With Complete Response or Partial Response (Objective Response), as Assessed by the Investigator
The rate of patients in objective response (complete or partial response) at 6 months according to the mRECIST criteria, and assessed according to the investigator. Response Evaluation Criteria In Solid Tumors Criteria (mRECIST v1.0) for target lesions wasassessed by MRI Complete Response (CR) was defined as : Disappearance of all target lesions and Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Objective Response was defind as the number of patients with a CR or a PR.
Measured: up to 6 months
Best Response According to mRECIST v1.0 in MRI
The best response according to the mRECIST criteria. Response Evaluation Criteria In Solid Tumors Criteria (mRECIST v1.0) for target lesions was assessed regarding all MRI done for patient during its treatment period.
Measured: up to 6 months after last chemoembolisation
Progression-Free Survival
It was defined by the time interval between the inclusion date and the date of the 1st progression according to the mRECIST criteria (assessed in central review) or death (regardless of the cause).
Alive patients without progression were censored at date of the last news.
Measured: up to 2 years
Overall Survival
It was defined by the time interval between the inclusion date and date of death (regardless of the cause) or date of the last news for alive patients.
Measured: up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2014 (estimated)
- Study startJan 2015
- Primary completionOct 2017
- Study completionOct 2017
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 Liver CancerStudies of the same condition, open and under way.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- Federation Francophone de Cancerologie Digestive
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Boris GUIU, PhD, Principal investigator, Fédération Francophone de Cancérologie Digestive
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02185768
- Sponsor's protocol ID
- FFCD 1307
- Acronym
- IDASPHERE II
- Status last verified
- Jun 2025
- First submitted
- 3 Jul 2014
- Last updated
- 4 Jul 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Guiu B, Chevallier P, Assenat E, Barbier E, Merle P, Bouvier A, Dumortier J, Nguyen-Khac E, Gugenheim J, Rode A, Oberti F, Valette PJ, Yzet T, Chevallier O, Barbare JC, Latournerie M, Boulin M. Idarubicin-loaded Beads for Chemoembolization of Hepatocellular Carcinoma: The IDASPHERE II Single-Arm Phase II Trial. Radiology. 2019 Jun;291(3):801-808. doi: 10.1148/radiol.2019182399. Epub 2019 Apr 30.
PubMed 31038408
Study at a glance
From the registry record, last updated by the sponsor on 4 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Chemoembolisation of Hepatocellular Carcinomas Not Subject to Interventive Care by Idarubicin-loaded Beads - IDASPHERE II
- ClinicalTrials.gov ID
- NCT02185768
- Acronym / sponsor ID
- IDASPHERE II / FFCD 1307
- Conditions
- Liver Cancer
- Keywords
- Liver cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 46 participants (actual)
- Lead sponsor
- Federation Francophone de Cancerologie DigestiveUniversity, hospital or other
- Study start
- Jan 2015 (actual)
- Primary completion
- Oct 2017 (actual)
- Study completion
- Oct 2017 (actual)
- First posted
- 10 Jul 2014 (estimated)
- Results
- Posted 15 Oct 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The most frequently used products in CHE are doxorubicin (36%), cisplatin (31%), and epirubicin (12%). But until recently, there were no obvious reasons to use one product over another. In fact, systemic chemotherapy is considered ineffective in HCC [hepatocellular carcinoma], which does not allow any argument in favour of the product. Moreover, 2 randomised trials comparing the molecules (doxorubicin vs. epirubicin) proved to be negative in terms of survival.
Cytotoxicity of different anticancer agents on HCC cell lines have been compared in order to select the best candidate for CHE. Eleven chemotherapy molecules have been tested, including those more frequently used in CHE. Among them, idarubicin (an anthracycline) proved to be the most effective in vitro by far. The superiority of idarubicin (as opposed to doxorubicin) was noted especially on the SNU-449 line, which is known for its resistance to several chemotherapy agents. The best cytotoxicity of idarubicin can be explained by 2 mechanisms: 1) idarubicin has a better intracellular penetration than the other anthracyclines. This is probably due to its more considerable lipophily, facilitating thus its passage through the membrane made up of a double lipid layer, 2) idarubicin is resistant to the multidrug resistance system (MDR). The MDR mechanism, which is often noted in HCC, consists of membrane pumps transporting the molecule outside the cell. These two particularities could explain a more significant accumulation of idarubicin in the HCC cells, and thus better efficacy. It is interesting to note that orally administered idarubicin (5 mg/day for 21 days) has proved to be less toxic and is effective in HCC. Currently, idarubicin is used to treat leukaemia. Its toxicity profile (especially, haematological and cardiac) is known.
On these grounds, A pilot study has been conducted in order to assess the tolerance and efficacy of lipiodol-based CHE using a 10 mg dose of idarubicin in 21 patients with unresectable HCC. These preliminary data reveal that CHE with idarubicin is effective and less toxic.
Idarubicin can be loaded in microbeads. A phase I study (IDASPHERE) has been conducted on DC Beads® microbeads (300-500µm) loaded with idarubicin (dose increased from 5 to 25 mg). The DLT [dose-limiting toxicity] and MTD [maximum tolerated dose] have been determined in 21 patients using a CRM. The MTD of idarubicin was assessed at 10 mg. In our study, the idarubicin-loaded beads did not give rise to any specific toxicity-related problem. The 10 mg dose is compatible with the known toxicity profile of idarubicin: cumulative cardiotoxicity of doxorubicin is noted from 550 mg/m², whereas that of idarubicin is noted from 93 mg/m². There is thus a 5.9:1 ratio between their cumulative toxicities. The most frequently used dose (and also the weakest one) for the doxorubicin-based CHE is 50 mg. The equivalent of the idarubicin dose would thus be: 50 mg (doxorubicin) / 5.9 (doxorubicin/idarubicin ratio) = approx. 10 mg of idarubicin.
It has been already demonstrated that hepatic extraction of idarubicin is better than those of doxorubicin and daunorubicin in an animal sarcoma model. In this study, AUC 0-48h and AUC 0-72h were 1.35 times higher with idarubicin, proving that its intra-hepatic penetration was 35% higher.
The randomised phase II PRECISION V study compared conventional CHE (cCHE) with CHE by doxorubicin beads (DC Bead®) in patients with HCC. It is currently the largest randomised trial on CHE published. The PRECISION V data can be thus used to compare the other studies in terms of efficacy and tolerance.
To continue our preliminary study and the phase I IDASPHERE study, investigators wish to assess thus the efficacy and confirm the tolerance of idarubicin-loaded beads for the CHE of HCC according to a protocol similar to PRECISION V, as part of a single-arm phase II study.
Detailed description
By using a 2-step Fleming plan (Fleming, 1982) with a unilateral alpha risk of 5% and 90% potency, it is necessary to include 86 assessable patients.
On the 1st step: 43 patients will be included (+/- 2 patients, if non-assessable patient(s)
- If 10 patients or less present an objective response, the trial will be discontinued on grounds of futility (H1 rejected)
- If 18 patients or less present an objective response, the trial will be discontinued on grounds of efficacy (H0 rejected)
If not, we proceed with the 2nd step including 43 additional patients. If 29 patients or more present an objective response, the treatment will be considered as effective (H0 rejected)
Considering a 5% ratio of visual loss or non-assessable patients, 91 patients will be included.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| DC-BEADS + Idarubicin | Experimental | Drug: idarubicin, Device: Dc- Beads 300-500µmChemoembolization with DC BEAD loaded with idarubicin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- - Histologically diagnosed HCC or HCC diagnosed according to the EASL criteria
- Measurable targets according to the mRECIST v1.1 criterion
- Preserved liver function (in case of Child-Pugh A or B7 cirrhosis)
- Tumour not subject to interventive care (liver transplant, surgical resection or percutaneous destruction)
- BCLC A/B without portal or extra-hepatic invasion
Key exclusion criteria (18 listed)
- - Advanced tumour (vascular or extra-hepatic invasion including brain metastasis or diffuse HCC with liver invasion > 50%)
- History of other type of cancer except cancer known to be in remission for more than 5 years (in this case, HCC histological proof is required), or basal-cell carcinoma or in situ cervix uteri cancer properly treated with curative treatment
- Advanced liver disease (Child B8, B9 and C, bilirubinaemia > 3 mg/dL, SGOT and SGPT > 5 x ULN or 250 U/L)
- Previous treatment by idarubicin and/or doxorubicin
- Idarubicin contraindications (cardiopathy with myocardial failure, serious kidney or liver failure, yellow fever vaccine)
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 |
|---|---|---|
| idarubicin | Drug | DC-BEADS + Idarubicin |
| Dc- Beads 300-500µm | Device | DC-BEADS + Idarubicin |
Primary outcome
Number of Participants With Complete Response or Partial Response (Objective Response), as Assessed According Central Review
Time frame: up to 6 months
The main judgement criterion is the rate of patients in objective response (complete or partial response) at 6 months according to the mRECIST criteria and based on the central review. Response Evaluation Criteria In Solid Tumors Criteria (mRECIST v1.0) for target lesions was assessed by MRI Complete Response (CR) was defined as : Disappearance of all target lesions and Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Objective Response was defind as the number of patients with a CR or a PR.
4 secondary outcomes
Number of Participants With Complete Response or Partial Response (Objective Response), as Assessed by the Investigator
Time frame: up to 6 months
Best Response According to mRECIST v1.0 in MRI
Time frame: up to 6 months after last chemoembolisation
Progression-Free Survival
Time frame: up to 2 years
Overall Survival
Time frame: up to 3 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jul 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 31038408Guiu B, Chevallier P, Assenat E, Barbier E, Merle P, Bouvier A, Dumortier J, Nguyen-Khac E, Gugenheim J, Rode A, Oberti F, Valette PJ, Yzet T, Chevallier O, Barbare JC, Latournerie M, Boulin M. Idarubicin-loaded Beads for Chemoembolization of Hepatocellular Carcinoma: The IDASPHERE II Single-Arm Phase II Trial. Radiology. 2019 Jun;291(3):801-808. doi: 10.1148/radiol.2019182399. Epub 2019 Apr 30.
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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.
Boris GUIU, PhD principal investigator
Fédération Francophone de Cancérologie Digestive
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing idarubicin and Dc- Beads 300-500µm in people with Liver Cancer, run by Federation Francophone de Cancerologie Digestive at 7 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 10 inclusion and 18 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 4 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 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.
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 15 Oct 2024). 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 Complete Response or Partial Response (Objective Response), as Assessed According Central Review (time frame: up to 6 months). 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 NCT02185768, 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 4 Jul 2025.