Comparison of Proton and Carbon Ion Radiotherapy With Advanced Photon Radiotherapy in Skull Base Meningiomas: The PINOCCHIO Trial. (PINOCCHIO)

Randomized Comparison of Proton and Carbon Ion Radiotherapy With Advanced Photon Radiotherapy in Skull Base Meningiomas: The PINOCCHIO Trial.

In PINOCCHIO-Triayl, carbon ion radiotherapy is compared to proton and advanced photon radiotherapy in patients with skull base meningiomas. There will be two treatment arms with photons, one arm with hypofractionated photon radiotherapy, and one arm with conventional fractionation. The study is designed as descriptive study on feasibility of the investigated therapies aiming at a comparison of toxicities. The study will serve as a basis for further larger randomized protocols comparing efficacy of the therapies, assuming toxicity is comparable in all four treatment arms. Primary endpoint is toxicity, secondary endpoints are overall survival, progression-free survival and quality of life.

Study Overview

• Status: Withdrawn
• Conditions: Skull Base Meningioma
• Intervention / Treatment: Radiation: Carbon Ion Radiotherapy; Radiation: Proton Therapy; Radiation: Hypofractionated Photon Radiotherapy; Radiation: Conventional Photon Radiotherapy

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Heidelberg, Germany, 69120
    • University Hospital of Heidelberg, Radiation Oncology

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

Patients meeting all of the following criteria will be considered for admission to the trial:

• Histologically or imaging confirmed skull base meningioma
• macroscopic tumor - Simpson Grade 4 or 5
• age ≥ 18 years of age
• Karnofsky Performance Score >=60
• For women with childbearing potential, (and men) adequate contraception (sexual abstinence, estrogen- or gestagen containing contraceptive medication etc.)
• Female participants: No pregnancy present (pregnancy test required)
• 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:

Patients presenting with any of the following criteria will not be included in the trial:

• refusal of the patients to take part in the study
• previous radiotherapy of the brain
• histologically confirmed atypical or anaplastic meningioma
• optic nerve sheath meningioma (ONSM)
• 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: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Carbon Ion Radiotherapy; Treatment Schedule Carbon Ion Radiation Total Dose 45 Gy E, 15 fractions, 3 Gy E single dose	Radiation: Carbon Ion Radiotherapy; Patients will be immobilized using an individually manufactured head mask for treatment planning and RT. Contrast-enhanced CT as well as MR-imaging will be performed for target volume definition. OAR such as the brain stem, optic nerves, chiasm and spinal chord will be contoured. The fractionation scheme will be taken into account for dose prescription, as well as DVH-characteristics and clinical parameters of the invidivual patient. The Gross Tumor Volume (GTV) will be defined as the contrast-enhancing lesion on MRI on T1-weighted MR-imaging. Amino-Acid-PET or DOTATOC-PET may be used in addition to contrast-enhanced MRI for target volume definition but is not mandatory.The Clinical Target Volume (CTV) will be defined adding 1-2mm safety margin to the GTV.
Experimental: Proton Therapy; Treatment Schedule Proton Radiation Total Dose 45 Gy E, 15 fractions, 3 Gy E single dose	Radiation: Proton Therapy; As described previously, patients will be immobilized using an individually manufactured head mask for treatment planning and RT. Contrast-enhanced CT as well as MR-imaging will be performed for target volume definition. OAR such as the brain stem, optic nerves, chiasm and spinal chord will be contoured. Dose constraints of normal tissue will be respected according to Emami et al. (33). The fractionation scheme will be taken into account for dose prescription, as well as DVH-characteristics and clinical parameters of the invidivual patient. The Gross Tumor Volume (GTV) will be defined as the contrast-enhancing lesion on MRI on T1-weighted MR-imaging. Amino-Acid-PET or DOTATOC-PET may be used in addition to contrast-enhanced MRI for target volume definition but is not mandatory.The Clinical Target Volume (CTV) will be defined adding 1-2mm safety margin to the GTV.
Experimental: Hypofractionated Photon Therapy; Treatment Schedule Photon Radiation 3 Gy E Total Dose 45 Gy E, 15 fractions, 3 Gy E single dose	Radiation: Hypofractionated Photon Radiotherapy; Treatment Planning for Photon Radiotherapy will be performed using the Planning Systems available at the Department of Radiation Oncology in Heidelberg, Germany (including Masterplan/Nucletron, Virtuos-Konrad/Siemens, or Precisis/STP/Stryker-Leibinger, or the Tomotherapy Software). Carbon ion and proton RT planning is performed using the treatment planning software PT-Planning (Siemens, Erlangen, Germany) including biologic plan optimization. Biologically effective dose distributions will be calculated using the a/ß ratio for meningioma as well as for the endpoint late toxicity to the brain. Patient positioning prior to radiotherapy will be evaluated by comparison of x-rays to the DRRs. Set up deviations >3mm are corrected prior to radiotherapy. To the target volume defined for photon treatment, a total dose of 52.2 Gy E - 57.6 Gy E is applied in single fractions of 1.8Gy E. In the 3Gy E Photon arm, photon radiotherapy will be delivered to a total dose of 45 Gy E in 15 fractions.
Active Comparator: Conventional Photon Radiotherapy; Treatment Schedule Photon Radiation 1.8 Gy E Total Dose 57.6 Gy Gy E, 32 fractions, 1.8 Gy E single dose	Radiation: Conventional Photon Radiotherapy; Treatment Planning for Photon Radiotherapy will be performed using the Planning Systems available at the Department of Radiation Oncology in Heidelberg, Germany (including Masterplan/Nucletron, Virtuos-Konrad/Siemens, or Precisis/STP/Stryker-Leibinger, or the Tomotherapy Software). Carbon ion and proton RT planning is performed using the treatment planning software PT-Planning (Siemens, Erlangen, Germany) including biologic plan optimization. Biologically effective dose distributions will be calculated using the a/ß ratio for meningioma as well as for the endpoint late toxicity to the brain. Patient positioning prior to radiotherapy will be evaluated by comparison of x-rays to the DRRs. Set up deviations >3mm are corrected prior to radiotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Toxicity graded according to CTCAE Version 4.1 after 1 year	Toxicity graded according to CTCAE Version 4.1 after 1 year	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Overall survival	3 years
Progression-free survival	Progression-free survival	3 years
Quality of Life		3 years

Collaborators and Investigators

• Sponsor: University Hospital Heidelberg

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2020
• Primary Completion (Anticipated): May 1, 2022
• Study Completion (Anticipated): May 1, 2022

Study Registration Dates

• First Submitted: February 18, 2013
• First Submitted That Met QC Criteria: February 18, 2013
• First Posted (Estimate): February 20, 2013

Study Record Updates

• Last Update Posted (Actual): October 6, 2021
• Last Update Submitted That Met QC Criteria: September 28, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• 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: pinocchio

Drug and device information, study documents

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