Clinical trial NCT02797366: Proton Radiotherapy for Primary Central Nervous System Tumours in Adults
Official title: Proton Radiotherapy for Primary Central Nervous System Tumours in Adults - a Prospective Swedish Multicentre Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Central Nervous System Tumour
Arteriovenous Malformation
Lead sponsor: Uppsala University
Sponsor class: OTHER
Collaborators: name: Sahlgrenska University Hospital
name: Karolinska University Hospital
name: University Hospital, Umeå
name: Region Örebro County
name: University Hospital, Linkoeping
First posted: 2016-06-13
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Acute adverse events
timeFrame: 3 months
measure: Long-term adverse events
timeFrame: 10-15 years
Secondary outcomes:
measure: Local and regional tumour control
timeFrame: 15 years
measure: Pattern of failure
timeFrame: 15 years
measure: Quality of life
timeFrame: 5 years
measure: Normal tissue sparing and normal tissue complication
timeFrame: 15 years
Other outcomes:
Locations:
city: Gothenburg
country: Sweden
facility: Sahlgrenska University Hospital
city: Linkoping
country: Sweden
facility: Linkoeping University Hospital
city: Orebro
country: Sweden
facility: Orebro University Hospital
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Umeå
country: Sweden
facility: Umea University Hospital
city: Uppsala
country: Sweden
facility: Uppsala University Hospital
Study officials:
affiliation: Uppsala University Hospital
name: Petra Witt Nystrom, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: