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Proton Radiotherapy for Primary Central Nervous System Tumours in Adults (PRO-CNS)

Primary Purpose

Central Nervous System Tumour, Arteriovenous Malformation

Status
Recruiting
Phase
Phase 2
Locations
Sweden
Study Type
Interventional
Intervention
Proton radiotherapy
Sponsored by
Uppsala University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Central Nervous System Tumour

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

  • The patient must be at least 18 years old
  • World Health Organization (WHO)/ Eastern Cooperative OncologyGroup (ECOG) performance status 0-2, Karnofsky score ≥60.
  • The patient must be able to understand the information about the treatment and give a written informed consent to participate in the trial.
  • Adequate follow-up study must be possible; this will exclude a patient who is uncooperative.
  • Must have a life expectancy of at least 3 years based on age and co-morbidities as well as diagnosis. For patients considered for re-irradiation the life expectancy must be estimated to minimum 6 months.
  • Must have a pathology proven CNS tumour or if not possible, the radiology findings must be evaluated at a multi-disciplinary conference at a university hospital.
  • Women of reproductive potential must agree to use an effective method of contraception during therapy such as an intrauterine device or condom. Pregnancy IS not an ineligibility criteria if radiotherapy is indicated and can-not be postponed.
  • Prior CNS radiotherapy is not an ineligibility criteria but re-irradiated patients will be included in a subgroup evaluated separately.

Patients discussed at multidisciplinary conferences at one of the seven university hospitals in Sweden and found candidates for radiotherapy and one of following diagnoses:

  • Anaplastic glioma grade III with Loss of Heterozygosity (LOH) 1p/19q and isocitrate dehydrogenase-1 (IDH-1) mutation
  • Arteriovenous malformations (AVMs)
  • Chordomas and chondrosarcomas
  • Craniopharyngiomas
  • Ependymomas
  • Intracranial germ cell tumours
  • Low grade gliomas - grade I-II
  • Medulloblastoma, Primitive neuroectodermal tumour (PNET)
  • Meningiomas
  • Neurocytoma
  • Other grade I-II primary CNS tumour according to WHO classification
  • Pituitary adenomas
  • Schwannomas
  • Spinal tumours
  • Whenever craniospinal irradiation (CSI) is indicated
  • Whenever re-irradiation of CNS is considered

Exclusion criteria:

  • Concomitant or previous malignancies. Exceptions are adequately treated basal cell carcinoma or squamous cell carcinoma of the skin, or in situ carcinoma of the cervix uteri with a follow-up time of at least 3 years, or other previous malignancy with a disease-free interval of at least 5 years.
  • Not able to understand information or manage tests according to study protocol. If necessary, only authorized interpreters may be used to assist in the translation.
  • Psychiatric or addictive disorders or other medical conditions that, in the opinions of the investigator, would preclude the patient from meeting the study requirements.

Sites / Locations

  • Sahlgrenska University HospitalRecruiting
  • Linkoeping University HospitalRecruiting
  • Orebro University HospitalRecruiting
  • Karolinska University HospitalRecruiting
  • Umea University HospitalRecruiting
  • Uppsala University HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Proton radiotherapy

Arm Description

Proton radiation therapy daily (Monday through Friday) for 4-8 weeks. This is a single arm study.

Outcomes

Primary Outcome Measures

Acute adverse events
Long-term adverse events
This study specifically includes longitudinal follow-up to assess the incidence of neurotoxicity including cognitive dysfunction, as well as the incidence of secondary malignant neoplasms at 10 and 15 years following radiotherapy.

Secondary Outcome Measures

Local and regional tumour control
Including overall survival
Pattern of failure
Pattern of failure on MRI will be compared with patients getting conventional radiotherapy.
Quality of life
Quality of Life (QoL) data will be evaluated using validated questionnaires from the European Organization for Research and Treatment of Cancer (EORTC): EORTC-QLQ-C30 is a multidimensional, cancer-specific QoL questionnaire developed for repeated assessments in clinical trials, and validated in various cancer populations. The Brain Cancer Module (EORTC-QLQ-BN20) includes 20 questions focusing on neurological symptoms and EuroQoL (EQ-5D) may additional also be used in the study.
Normal tissue sparing and normal tissue complication
Normal tissue complication probability (NTCP) models will be used to evaluate the reduction in normal tissue complications in dose planning studies comparing proton radiotherapy vs. 3D-Conformal Radiotherapy (CRT), Intensity Modulated Radiotherapy (IMRT)/Volumetric Modulated Arc Therapy (VMAT)/Helical Tomotherapy (HTT).

Full Information

First Posted
May 18, 2016
Last Updated
June 7, 2016
Sponsor
Uppsala University
Collaborators
Sahlgrenska University Hospital, Sweden, Karolinska University Hospital, University Hospital, Umeå, Region Örebro County, University Hospital, Linkoeping
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1. Study Identification

Unique Protocol Identification Number
NCT02797366
Brief Title
Proton Radiotherapy for Primary Central Nervous System Tumours in Adults
Acronym
PRO-CNS
Official Title
Proton Radiotherapy for Primary Central Nervous System Tumours in Adults - a Prospective Swedish Multicentre Study
Study Type
Interventional

2. Study Status

Record Verification Date
June 2016
Overall Recruitment Status
Recruiting
Study Start Date
August 2015 (undefined)
Primary Completion Date
July 2020 (Anticipated)
Study Completion Date
July 2030 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Uppsala University
Collaborators
Sahlgrenska University Hospital, Sweden, Karolinska University Hospital, University Hospital, Umeå, Region Örebro County, University Hospital, Linkoeping

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Open label, multi-centre prospective study. Adult patients with primary central nervous system tumours fulfilling the inclusion criteria according to the study protocol. The study consists of 2 sequential cohorts evaluated consecutively for the feasibility, safety and toxicity, as well as long-term survival data, when using spot scanning proton beam therapy.
Detailed Description
Open label, multi-centre prospective phase II study. Adult patients with primary central nervous system tumours full-filling the inclusion criteria according to the study protocol. The study consists of 2 sequential cohorts evaluated for the feasibility, safety and toxicity, as well as long-term survival data, when using proton beam therapy. Part I: To assess the feasibility of using pencil beam scanning and evaluating the treatment safety in all aspects, and to assess acute toxicity in a smaller cohort of CNS patients. All toxicity data, QoL and survival data will also be included in the part II cohort. Part II: The second part of the trial consists of all CNS patients that are referred to the Skandion Clinic after the safety data from the first part has been evaluated by the study steering committee.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Central Nervous System Tumour, Arteriovenous Malformation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
500 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Proton radiotherapy
Arm Type
Other
Arm Description
Proton radiation therapy daily (Monday through Friday) for 4-8 weeks. This is a single arm study.
Intervention Type
Radiation
Intervention Name(s)
Proton radiotherapy
Primary Outcome Measure Information:
Title
Acute adverse events
Time Frame
3 months
Title
Long-term adverse events
Description
This study specifically includes longitudinal follow-up to assess the incidence of neurotoxicity including cognitive dysfunction, as well as the incidence of secondary malignant neoplasms at 10 and 15 years following radiotherapy.
Time Frame
10-15 years
Secondary Outcome Measure Information:
Title
Local and regional tumour control
Description
Including overall survival
Time Frame
15 years
Title
Pattern of failure
Description
Pattern of failure on MRI will be compared with patients getting conventional radiotherapy.
Time Frame
15 years
Title
Quality of life
Description
Quality of Life (QoL) data will be evaluated using validated questionnaires from the European Organization for Research and Treatment of Cancer (EORTC): EORTC-QLQ-C30 is a multidimensional, cancer-specific QoL questionnaire developed for repeated assessments in clinical trials, and validated in various cancer populations. The Brain Cancer Module (EORTC-QLQ-BN20) includes 20 questions focusing on neurological symptoms and EuroQoL (EQ-5D) may additional also be used in the study.
Time Frame
5 years
Title
Normal tissue sparing and normal tissue complication
Description
Normal tissue complication probability (NTCP) models will be used to evaluate the reduction in normal tissue complications in dose planning studies comparing proton radiotherapy vs. 3D-Conformal Radiotherapy (CRT), Intensity Modulated Radiotherapy (IMRT)/Volumetric Modulated Arc Therapy (VMAT)/Helical Tomotherapy (HTT).
Time Frame
15 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria: The patient must be at least 18 years old World Health Organization (WHO)/ Eastern Cooperative OncologyGroup (ECOG) performance status 0-2, Karnofsky score ≥60. The patient must be able to understand the information about the treatment and give a written informed consent to participate in the trial. Adequate follow-up study must be possible; this will exclude a patient who is uncooperative. Must have a life expectancy of at least 3 years based on age and co-morbidities as well as diagnosis. For patients considered for re-irradiation the life expectancy must be estimated to minimum 6 months. Must have a pathology proven CNS tumour or if not possible, the radiology findings must be evaluated at a multi-disciplinary conference at a university hospital. Women of reproductive potential must agree to use an effective method of contraception during therapy such as an intrauterine device or condom. Pregnancy IS not an ineligibility criteria if radiotherapy is indicated and can-not be postponed. Prior CNS radiotherapy is not an ineligibility criteria but re-irradiated patients will be included in a subgroup evaluated separately. Patients discussed at multidisciplinary conferences at one of the seven university hospitals in Sweden and found candidates for radiotherapy and one of following diagnoses: Anaplastic glioma grade III with Loss of Heterozygosity (LOH) 1p/19q and isocitrate dehydrogenase-1 (IDH-1) mutation Arteriovenous malformations (AVMs) Chordomas and chondrosarcomas Craniopharyngiomas Ependymomas Intracranial germ cell tumours Low grade gliomas - grade I-II Medulloblastoma, Primitive neuroectodermal tumour (PNET) Meningiomas Neurocytoma Other grade I-II primary CNS tumour according to WHO classification Pituitary adenomas Schwannomas Spinal tumours Whenever craniospinal irradiation (CSI) is indicated Whenever re-irradiation of CNS is considered Exclusion criteria: Concomitant or previous malignancies. Exceptions are adequately treated basal cell carcinoma or squamous cell carcinoma of the skin, or in situ carcinoma of the cervix uteri with a follow-up time of at least 3 years, or other previous malignancy with a disease-free interval of at least 5 years. Not able to understand information or manage tests according to study protocol. If necessary, only authorized interpreters may be used to assist in the translation. Psychiatric or addictive disorders or other medical conditions that, in the opinions of the investigator, would preclude the patient from meeting the study requirements.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Petra Witt Nystrom, MD, PhD
Email
petra.witt@akademiska.se
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Petra Witt Nystrom, MD, PhD
Organizational Affiliation
Uppsala University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sahlgrenska University Hospital
City
Gothenburg
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Katja Werlenius, MD
Facility Name
Linkoeping University Hospital
City
Linkoping
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anna Flejmer, MD
Facility Name
Orebro University Hospital
City
Orebro
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eva Tegnelius, MD
Facility Name
Karolinska University Hospital
City
Stockholm
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Teresa Herlestam-Carlero, MD, PhD
Facility Name
Umea University Hospital
City
Umeå
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Per Bergstrom, MD
Facility Name
Uppsala University Hospital
City
Uppsala
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Petra Witt Nyström, Md, PhD

12. IPD Sharing Statement

Learn more about this trial

Proton Radiotherapy for Primary Central Nervous System Tumours in Adults

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