Hepatocellular CarcinomaPROMETHEUS-01NCT01167374
Carbon Ion Radiotherapy for Hepatocellular Carcinoma
A study testing Carbon Ion Radiotherapy in people with Hepatocellular Carcinoma, run by University Hospital Heidelberg at 1 site in Germany.
Trial summary
Treatment options for patients with advanced hepatocellular carcinoma (HCC) are often limited. In most cases, they are not amenable to local therapies including surgery or radiofrequency ablation. The multi-kinase inhibitor sorafenib has shown to increase overall survival in this patient group for about 3 months. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- Carbon Ion Radiotherapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteGermany
- Study dates
- Aug 2011to Aug 2022
- Phase
- Interventional
- 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
Who may be able to join
- histologically confirmed HCC or diagnosis of HCC according to AASLD-guidelines
- macroscopic tumor
- liver-confined disease without extrahepatic disease as diagnosed by CT, MRT, ultrasound and bone scan
- minimal distance of tumor edge to the intestines of 1cm
- age ≥ 18 years of age
- Karnofsky Performance Score ³60
Show all 9Show fewer
- For women with childbearing potential, (and men) adequate contraception.
- Ability of subject to understand character and individual consequences of the clinical trial
- Written informed consent (must be available before enrolment in the trial)
Who cannot join
- refusal of the patients to take part in the study
- previous radiotherapy of the hepatobiliary system
- margin of < 1cm between tumor edge and intestines
- Patients who have not yet recovered from acute toxicities of prior therapies
- Known carcinoma < 2 years ago (excluding Carcinoma in situ of the cervix, basal cell carcinoma, squamous cell carcinoma of the skin) requiring immediate treatment interfering with study therapy
- Pregnant or lactating women
- Participation in another clinical study or observation period of competing trials, respectively
Trial locations and contacts
1 site in 1 country.
Germany1 site
University Hospital of Heidelberg, Radiation Oncology
Heidelberg, 69120
About this study
Official title: Phase I Study Evaluating the Treatment of Patients With Hepatocellular Carcinoma (HCC) With Carbon Ion Radiotherapy
Treatment options for patients with advanced hepatocellular carcinoma (HCC) are often limited. In most cases, they are not amenable to local therapies including surgery or radiofrequency ablation. The multi-kinase inhibitor sorafenib has shown to increase overall survival in this patient group for about 3 months.
Radiation therapy is a treatment alternative, however, high local doses are required for long-term local control. However, due to the relatively low radiation tolerance of liver normal tissue, even using stereotactic techniques, delivery of sufficient doses for successful local tumor control has not be achieved to date.
Read more
Carbon ions offer physical and biological characteristics. Due to their inverted dose profile and the high local dose deposition within the Bragg peak precise dose application and sparing of normal tissue is possible. Moreover, in comparison to photons, carbon ions offer an increased relative biological effectiveness (RBE), which can be calculated between 2 and 3 depending on the HCC cell line as well as the endpoint analyzed.
Japanese Data on the evaluation of carbon ion radiation therapy showed promising results for patients with HCC.
In the current Phase I-PROMETHEUS-01-Study, carbon ion radiotherapy will be evaluated for patients with advanced HCC. The study will be performed as a dose-escalation study evaluating the optimal carbon ion dose with respect to toxicity and tumor control.
Primary endpoint is toxicity, secondary endpoint is progression-free survival and response.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- Carbon Ion Radiotherapy
- Keywords
- HCC
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Carbon Ion RadiotherapyRadiation
Increasing Dose of Carbon Ion Radiotherapy 4 x 10 Gy E to 4 x 14 Gy E
| Study group | Role | What they receive |
|---|---|---|
| Carbon Ion Radiotherapy | Experimental | Increasing Dose of Carbon Ion Radiotherapy 4 x 10 Gy E to 4 x 14 Gy E Receives: Radiation: Carbon Ion Radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD)
Determination the maximum tolerated dose (MTD) and dose limiting toxicities (DLTs) of carbon ion radiotherapy
Measured: 3 months
Secondary outcomes (1)
Progression-free Survival
Measured: Follow-up until progression up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2010 (estimated)
- Study startAug 2011
- Primary completionAug 2022
- Study completionAug 2022
Why it stopped: Slow recruitment rate
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by University Hospital HeidelbergThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Heidelberg
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Juergen Debus, University Hospital Heidelberg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01167374
- Sponsor's protocol ID
- PROMETHEUS-01
- Acronym
- PROMETHEUS-01
- Status last verified
- Nov 2022
- First submitted
- 20 Jul 2010
- Last updated
- 3 Nov 2022
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Hoegen-Sassmannshausen P, Naumann P, Hoffmeister-Wittmann P, Ben Harrabi S, Seidensaal K, Weykamp F, Mielke T, Ellerbrock M, Habermehl D, Springfeld C, Dill MT, Longerich T, Schirmacher P, Mehrabi A, Chang DH, Horner-Rieber J, Jakel O, Haberer T, Combs SE, Debus J, Herfarth K, Liermann J. Carbon ion radiotherapy of hepatocellular carcinoma provides excellent local control: The prospective phase I PROMETHEUS trial. JHEP Rep. 2024 Mar 11;6(6):101063. doi: 10.1016/j.jhepr.2024.101063. eCollection 2024 Jun.
PubMed 38737600Habermehl D, Debus J, Ganten T, Ganten MK, Bauer J, Brecht IC, Brons S, Haberer T, Haertig M, Jakel O, Parodi K, Welzel T, Combs SE. Hypofractionated carbon ion therapy delivered with scanned ion beams for patients with hepatocellular carcinoma - feasibility and clinical response. Radiat Oncol. 2013 Mar 13;8:59. doi: 10.1186/1748-717X-8-59.
PubMed 23497349Combs SE, Habermehl D, Ganten T, Schmidt J, Edler L, Burkholder I, Jakel O, Haberer T, Debus J. Phase i study evaluating the treatment of patients with hepatocellular carcinoma (HCC) with carbon ion radiotherapy: the PROMETHEUS-01 trial. BMC Cancer. 2011 Feb 12;11:67. doi: 10.1186/1471-2407-11-67.
PubMed 21314962
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study Evaluating the Treatment of Patients With Hepatocellular Carcinoma (HCC) With Carbon Ion Radiotherapy
- ClinicalTrials.gov ID
- NCT01167374
- Acronym / sponsor ID
- PROMETHEUS-01 / PROMETHEUS-01
- Conditions
- Hepatocellular Carcinoma
- Keywords
- HCC
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow recruitment rate
- Enrolment
- 21 participants (actual)
- Lead sponsor
- University Hospital HeidelbergUniversity, hospital or other
- Study start
- Aug 2011 (actual)
- Primary completion
- Aug 2022 (actual)
- Study completion
- Aug 2022 (actual)
- First posted
- 22 Jul 2010 (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.
Treatment options for patients with advanced hepatocellular carcinoma (HCC) are often limited. In most cases, they are not amenable to local therapies including surgery or radiofrequency ablation. The multi-kinase inhibitor sorafenib has shown to increase overall survival in this patient group for about 3 months.
Radiation therapy is a treatment alternative, however, high local doses are required for long-term local control. However, due to the relatively low radiation tolerance of liver normal tissue, even using stereotactic techniques, delivery of sufficient doses for successful local tumor control has not be achieved to date.
Carbon ions offer physical and biological characteristics. Due to their inverted dose profile and the high local dose deposition within the Bragg peak precise dose application and sparing of normal tissue is possible. Moreover, in comparison to photons, carbon ions offer an increased relative biological effectiveness (RBE), which can be calculated between 2 and 3 depending on the HCC cell line as well as the endpoint analyzed.
Japanese Data on the evaluation of carbon ion radiation therapy showed promising results for patients with HCC.
In the current Phase I-PROMETHEUS-01-Study, carbon ion radiotherapy will be evaluated for patients with advanced HCC. The study will be performed as a dose-escalation study evaluating the optimal carbon ion dose with respect to toxicity and tumor control.
Primary endpoint is toxicity, secondary endpoint is progression-free survival and response.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Carbon Ion Radiotherapy | Experimental | Radiation: Carbon Ion RadiotherapyIncreasing Dose of Carbon Ion Radiotherapy 4 x 10 Gy E to 4 x 14 Gy E |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- histologically confirmed HCC or diagnosis of HCC according to AASLD-guidelines
- macroscopic tumor
- liver-confined disease without extrahepatic disease as diagnosed by CT, MRT, ultrasound and bone scan
- minimal distance of tumor edge to the intestines of 1cm
- age ≥ 18 years of age
Key exclusion criteria (7 listed)
- refusal of the patients to take part in the study
- previous radiotherapy of the hepatobiliary system
- margin of < 1cm between tumor edge and intestines
- Patients who have not yet recovered from acute toxicities of prior therapies
- Known carcinoma < 2 years ago (excluding Carcinoma in situ of the cervix, basal cell carcinoma, squamous cell carcinoma of the skin) requiring immediate treatment interfering with study 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 |
|---|---|---|
| Carbon Ion RadiotherapyIncreasing Dose of Carbon Ion Radiotherapy 4 x 10 Gy E to 4 x 14 Gy E | Radiation | Carbon Ion Radiotherapy |
Primary outcome
Maximum Tolerated Dose (MTD)
Time frame: 3 months
Determination the maximum tolerated dose (MTD) and dose limiting toxicities (DLTs) of carbon ion radiotherapy
1 secondary outcome
Progression-free Survival
Time frame: Follow-up until progression up to 12 months
Results and safety
The study was stopped early (reason given: Slow recruitment rate). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2022.
- Derived from this study: PubMed 38737600Hoegen-Sassmannshausen P, Naumann P, Hoffmeister-Wittmann P, Ben Harrabi S, Seidensaal K, Weykamp F, Mielke T, Ellerbrock M, Habermehl D, Springfeld C, Dill MT, Longerich T, Schirmacher P, Mehrabi A, Chang DH, Horner-Rieber J, Jakel O, Haberer T, Combs SE, Debus J, Herfarth K, Liermann J. Carbon ion radiotherapy of hepatocellular carcinoma provides excellent local control: The prospective phase I PROMETHEUS trial. JHEP Rep. 2024 Mar 11;6(6):101063. doi: 10.1016/j.jhepr.2024.101063. eCollection 2024 Jun.
- Derived from this study: PubMed 23497349Habermehl D, Debus J, Ganten T, Ganten MK, Bauer J, Brecht IC, Brons S, Haberer T, Haertig M, Jakel O, Parodi K, Welzel T, Combs SE. Hypofractionated carbon ion therapy delivered with scanned ion beams for patients with hepatocellular carcinoma - feasibility and clinical response. Radiat Oncol. 2013 Mar 13;8:59. doi: 10.1186/1748-717X-8-59.
- Derived from this study: PubMed 21314962Combs SE, Habermehl D, Ganten T, Schmidt J, Edler L, Burkholder I, Jakel O, Haberer T, Debus J. Phase i study evaluating the treatment of patients with hepatocellular carcinoma (HCC) with carbon ion radiotherapy: the PROMETHEUS-01 trial. BMC Cancer. 2011 Feb 12;11:67. doi: 10.1186/1471-2407-11-67.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Carbon Ion Radiotherapy in people with Hepatocellular Carcinoma, run by University Hospital Heidelberg at 1 site in Germany.
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 9 inclusion and 7 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: stopped early, as of the sponsor's last update on 3 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. 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 was stopped early (reason given: Slow recruitment rate). Results are not available in the source record.
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 (MTD) (time frame: 3 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 NCT01167374, which also lists 3 linked publications.
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 3 Nov 2022.