Carbon Ion Radiotherapy for Hepatocellular Carcinoma

NCT ID: NCT01167374

Last Updated: 2022-11-03

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-08-31
• Study Completion Date: 2022-08-31

Brief 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.

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.

Conditions

Hepatocellular Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Carbon Ion Radiotherapy

Increasing Dose of Carbon Ion Radiotherapy 4 x 10 Gy E to 4 x 14 Gy E

Group Type: EXPERIMENTAL

Carbon Ion Radiotherapy

Intervention Type: RADIATION

Increasing Dose of Carbon Ion Radiotherapy 4 x 10 Gy E to 4 x 14 Gy E

Interventions

Carbon Ion Radiotherapy

Increasing Dose of Carbon Ion Radiotherapy 4 x 10 Gy E to 4 x 14 Gy E

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• 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
• 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)

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital Heidelberg

OTHER

Sponsor Role: lead

Responsible Party

Juergen Debus

Prof. Dr. Dr. Jürgen Debus

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University Hospital of Heidelberg, Radiation Oncology

Heidelberg, , Germany

Countries

Germany

References

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.

Reference Type: DERIVED

PMID: 38737600 (View on PubMed)

Habermehl 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.

Reference Type: DERIVED

PMID: 23497349 (View on PubMed)

Combs 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.

Reference Type: DERIVED

PMID: 21314962 (View on PubMed)

Other Identifiers

PROMETHEUS-01

Identifier Type: -

Identifier Source: org_study_id