Carbon Ion Radiotherapy for Atypical Meningiomas (MARCIE)

Treatment of Patients With Atypical Meningiomas Simpson Grade 4 and 5 With a Carbon Ion Boost in Combination With Postoperative Photon Radiotherapy: A Phase II Trial

Treatment standard for patients with atypical or anaplastic meningioma is neurosurgical resection. With this approach, local control ranges between 50 and 70%, depending on resection status. A series or smaller studies has shown that postoperative radiotherapy in this patient population can increase progression-free survival, which translates into increased overall survival. However, meningiomas are known to be radioresistant tumors, and radiation doses of 60 Gy or higher have been shown to be necessary for tumor control.

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 5 depending on the cell line as well as the endpoint analyzed.

First data obtained within the Phase I/II trial performed at GSI in Darmstadt on carbon ion radiotherapy for patients with high-risk meningiomas has shown safety, and treatment results are promising.

Therefore, in the current Phase II-MARCIE-Study a carbon ion boost will be applied to the macroscopic tumor (gross tumor volume, GTV) in conjunction with photon radiotherapy to the clinical target volume (CTV) in patients with atypical meningiomas after incomplete resection or biopsy.

Primary endpoint is progression-free survival rate, secondary endpoints are overall survival, safety and toxicity.

Study Overview

• Status: Active, not recruiting
• Conditions: Meningioma
• Intervention / Treatment: Radiation: Carbon Ion Radiotherapy

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Heidelberg, Germany, 69120
    • University Hopsital Heidelberg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• histologically confirmed atypical meningioma
• macroscopic tumor after biopsy or subtotal resection
• Simpson Grade 4 or 5
• prior photon radiotherapy to the clinical target volume (CTV) of 48-52 Gy
• beginning of study treatment no later than 12 weeks after surgery
• age ≥ 18 years of age
• Karnofsky Performance Score ≥ 60
• For women with childbearing potential, 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 brain
• optic nerve sheath meningioma (ONSM)
• time interval of > 12 weeks after primary diagnosis (neurosurgical intervention) and beginning of study treatment
• Patients who have not yet recovered from acute toxicities of prior therapies
• Known carcinoma < 5 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Carbon Ion Radiotherapy Boost; Carbon Ion Boost to the Macroscopic Tumor visible on contrast-enhanced MR-Imaging	Radiation: Carbon Ion Radiotherapy; Carbon Ion Boost 18 Gy E in single Fractions of 3 Gy E

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression-free survival	Progression-free survival at 3 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall Survival	Overall Survival at 3 years

Collaborators and Investigators

• Sponsor: University Hospital Heidelberg

Publications and helpful links

General Publications

• Combs SE, Edler L, Burkholder I, Rieken S, Habermehl D, Jakel O, Haberer T, Unterberg A, Wick W, Debus J, Haselmann R. Treatment of patients with atypical meningiomas Simpson grade 4 and 5 with a carbon ion boost in combination with postoperative photon radiotherapy: the MARCIE trial. BMC Cancer. 2010 Nov 9;10:615. doi: 10.1186/1471-2407-10-615.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2012
• Primary Completion (Actual): July 1, 2020
• Study Completion (Estimated): February 1, 2026

Study Registration Dates

• First Submitted: July 20, 2010
• First Submitted That Met QC Criteria: July 20, 2010
• First Posted (Estimated): July 21, 2010

Study Record Updates

• Last Update Posted (Actual): January 5, 2024
• Last Update Submitted That Met QC Criteria: January 4, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Atypical Meningioma
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms, Vascular Tissue; Meningeal Neoplasms; Meningioma
• Other Study ID Numbers: MARCIE; 2009-016683-36 (EudraCT Number)