Proton Dose Escalation for Patients With Atypical or Anaplastic Meningiomas (PANAMA)

The trial evaluates the effect of a moderately increased radiation dose in patients with atypical (grade II) and anaplastic (grade III) meningioma after incomplete or no surgery. Endpoint is recurrence-free survival after 5 years.

Study Overview

• Status: Not yet recruiting
• Conditions: Meningioma
• Intervention / Treatment: Radiation: Radiotherapy 68 Gy(RBE); Radiation: Radiotherapy 72 Gy(RBE); Radiation: Radiotherapy 60 Gy(RBE)

Detailed Description

The trial intends to optimize treatment for grade II and grade III (atypical or anaplastic) meningioma. Standard treatment for atypical or anaplastic meningioma is surgery. For grade III (anaplastic) meningiomas, post-operative radiotherapy would be performed in all cases using standard fractionation schedules to a total dose of ~60 Gy. For grade II (atypical) meningiomas, although some small patient datasets support early onset of radiotherapy, the standard treatment is still to irradiate if tumours are recurrent or if resection was macroscopically incomplete. Total doses of 54 to ~60 Gy are applied using standard fractionation schedules.

A major problem of the treatment of atypical or anaplastic meningioma is that beyond surgery and radiotherapy, there are only experimental treatment options and the probability of local recurrences is 50-100% within the first 5 years for grade II and grade III meningioma.

The present trial has been developed to evaluate efficacy of a dose-intensified radiotherapy treatment schedule for incompletely or not resected meningioma to a total dose of 68 (grade II) or 72 Gy (grade III). To minimize normal tissue toxicity, the boost dose or the complete radiotherapy is applied using protons. The expectation is a higher recurrence-free survival compared to previous reports on outcome of standard dose (60 Gy) radiotherapy.

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• histologically confirmed atypical (WHO grade II) or anaplastic (WHO grade III) meningioma with the indication for radiotherapy
• MRI (within 24h post-operative, if not available than with a time interval of ~ 6 weeks) including contrast-enhanced T1 weighted 3D dataset and PET for evaluation of macroscopic tumour (residuum)
• Karnofsky Performance Score ≥ 60, ECOG ≤2
• 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 brain
• several manifestations of the meningioma in different regions of the brain or additional spinal manifestations
• distant metastases
• patients who are not suitable for radiotherapy
• known other malignant disease within 5 years before radiotherapy (except tumours that likely do not impact prognosis and likely not require treatment interfering with study therapy, e.g. in-situ carcinoma of the breast or cervix uteri)
• pregnant or lactating women
• patients with non-MRI compatible metal implants, pacemaker or non-MRI compatible external automatic defibrillators
• patients not able to understand character and individual consequences of the clinical trial
• claustrophobic patients
• current participation in another clinical intervention study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Grade II tumors (macroscopic); Radiotherapy 68 Gy(RBE)	Radiation: Radiotherapy 68 Gy(RBE); Radiotherapy 2.0 to 50 Gy(RBE) photon or proton and boost 2 to 18 Gy(RBE) proton
Experimental: Grade III tumors (macroscopic); Radiotherapy 72 Gy(RBE)	Radiation: Radiotherapy 72 Gy(RBE); Radiotherapy 2.0 to 50 Gy(RBE) photon or proton and boost 2 to 18 Gy(RBE) proton and boost 2 to 4 Gy(RBE) proton
Active Comparator: Grade II/III tumors (completely resected); Radiotherapy 60 Gy(RBE)	Radiation: Radiotherapy 60 Gy(RBE); Radiotherapy 2.0 to 50 Gy(RBE) photon or proton and boost 2 to 10 Gy(RBE) proton

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
progression-free survival	5 years after start of radiotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
late toxicity	CTC-AE 4.0	5 years after start of radiotherapy
acute toxicity	CTC-AE 4.0	5 years after start of radiotherapy
overall survival		5 years after start of radiotherapy
patterns of recurrence using MRI		5 years after start of radiotherapy
quality of life by validated quality of life questionnaires	EORTC-QLQ-C30, EORTC-QLQ-BN20	5 years after start of radiotherapy

Collaborators and Investigators

• Sponsor: Technische Universität Dresden
• Collaborators: German Cancer Research Center; Radiation Oncology Working Group of the German Cancer Society
• Investigators: Study Chair: Mechthild Krause, Prof., Technische Universität Dresden, German Cancer Consortium, Helmholtz-Zentrum Dresden - Rossendorf

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2022
• Primary Completion (Anticipated): December 1, 2028
• Study Completion (Anticipated): December 1, 2029

Study Registration Dates

• First Submitted: October 19, 2016
• First Submitted That Met QC Criteria: November 28, 2016
• First Posted (Estimate): December 1, 2016

Study Record Updates

• Last Update Posted (Actual): August 3, 2022
• Last Update Submitted That Met QC Criteria: August 2, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: brain tumors; proton radiotherapy; photon radiotherapy
• 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: STR-PANAMA-2015

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No