Clinical trial NCT04670016: HRQL and Symptom Assessment for Patients With DIPG or Recurrent and Re-irradiated Brain Tumours and Their Caregivers
Official title: Health Related Quality of Life (HRQL) and Symptom Assessment in Patients Diagnosed With Diffuse Intrinsic Pontine Glioma (DIPG) or Recurrent and Re-irradiated Brain Tumours and Their Caregivers: A Non-Therapeutic Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: DIPG
Brain Tumor, Pediatric, Recurrent
Brain Tumor, DIPG
Radiation Toxicity
Radiation Exposure
Brain Tumor, Pediatric
Keywords: health-related quality of life
psychosocial
re-irradiation
DIPG
pediatric brain tumor
Lead sponsor: University of Calgary
Sponsor class: OTHER
Collaborators: name: University of Toronto
name: Université de Montréal
name: University of Ottawa
name: Western University, Canada
name: McMaster University
name: Alberta Children's Hospital
name: Stollery Children's Hospital
name: British Columbia Children's Hospital
name: CancerCare Manitoba
name: Children's Hospital of Eastern Ontario
name: The Hospital for Sick Children
name: McMaster Children's Hospital
name: Children's Hospital Medical Center, Cincinnati
name: St. Justine's Hospital
name: Montreal Children's Hospital of the MUHC
name: IWK Health Centre
name: Janeway Children's Health and Rehabilitation Centre
name: Princess Margaret Hospital, Canada
name: London Health Sciences Centre
name: The Ottawa Hospital
name: CHU de Quebec-Universite Laval
First posted: 2020-12-17
Enrollment: 57
Sex: ALL
Minimum age (years): 2
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Up to 30 patients diagnosed with DIPG and up to 32 patients diagnosed with another recurrent or progressive brain tumor will be enrolled in this study.

There will be no registration on study for screening purposes only. Eligible patients who consent to this study therapy will be registered at the PI's institution, specifically with the PI's research coordinator. A study subject number will be assigned to the patient upon registration.

Brief summary: Although many children with brain tumours are successfully cured of their disease, a substantial proportion of patients suffer disease recurrence and require further treatment. This therapy may involve a repeat course of radiation (RT2). Based on retrospective data, re-irradiation may provide palliative and even potentially curative benefit. However, such retrospective data are subject to bias, which may over-report survival and under-report toxicity. Furthermore, we do not know how re-irradiation affects patients' HRQOL. The goal of this research is to prospectively describe the HRQOL of patients diagnosed with DIPG and recurrent brain tumors and their families before and after re-irradiation to more accurately assess the benefit versus the toxicity of this treatment.

In addition, if we are able to demonstrate the feasibility of collecting HRQOL information on a routine basis we will be able to justify the need to conduct this research further and implement HRQOL screening as a standard of care for these patients. Re-irradiation for children with DIPG and recurrent brain tumours will not cure these children from their disease but may improve neurological function and wellbeing. We postulate that the opportunity of more time to say the final good bye and creating memories will facilitate bereavement and prevent psychological dysfunction of parents and siblings. A greater understanding of what helps these families may enable clinicians to better support these children and their families in this difficult disease course. Ultimately our goal is to improve the psychological experience of these patients and their families.

Detailed description: Many children diagnosed with brain tumours are at significant risk of disease recurrence following their initial treatment, with recurrence rates ranging from 30-100% depending on the type of brain tumour. Disease recurrence represents a serious clinical issue in brain tumour patients and when this occurs, additional treatment is needed. These treatments may result in further damage to the surrounding normal brain tissue, resulting in neurocognitive decline (brain or mental function) and reduced quality of life. A novel treatment option for these patients is to administer a second course of radiation (re-irradiation). However, the effects of re-irradiation on quality-of-life are poorly studied. This study aims to increase the knowledge surrounding re-irradiation, particularly with regards to HRQOL.

The primary objective of the proposed study is to describe the HRQOL and symptoms for children diagnosed with DIPG or recurrent brain tumours treated with repeat radiation and their caregivers over time.

We have four Aims. Aim 1: To describe the HRQOL trajectory and symptoms for children diagnosed with DIPG and in children treated with re-irradiation for a recurrent brain tumour and their caregivers over time. Aim 2: To identify critical time points of HRQOL difficulty across the trajectory of DIPG/recurrent brain tumour treatment and to ascertain demographic and/or medical sequelae that are related to HRQOL outcomes. Aim 3: To determine the feasibility of conducting routine assessment of HRQL in children diagnosed with DIPG/recurrent brain tumours and their caregivers based on recruitment and retention rates. Aim 4: To report the incidence of radiation necrosis (RN), local control, progression-free survival and overall survival after re-irradiation.

Our goal to is enroll 25 to 30 patient/caregiver dyads diagnosed with DIPG and 32 patient/caregiver dyads treated with re-RT for a recurrent/progressive brain tumour onto the trial over the study period and to follow patients until their disease progresses again, which has been, on average, 6 months after completion of RT2.

Once deemed eligible, individual patient recruitment will be the responsibility of the institution Clinical Research Assistant (CRA). Upon consenting to take part in the study, patients and families will be contacted using an online administration and scoring program. HRQOL assessments will take 15-25 minutes to complete at each time point. Baseline questionnaires will be completed at the time of recurrence or progressive DIPG or other brain tumor (+/- 7 days from start of treatment, maximum 14 days). Patients will then complete HRQOL measures at the end of re-irradiation and then again every two months.

Necrosis and local tumour control will be assessed using MRI ordered as part of standard-of-care follow-up (recommended scan interval every 3-6 months until 5 years post-treatment). Necrosis and other toxicities, if present without evidence of disease recurrence, will be graded at baseline and each post-RT2 standard-of-care visit using CTCAE v5.0 (a rating scale of side effects). Steroid use and Lansky play score will be recorded at each visit. Progression and death will be collected from the health record. Re-irradiation dosimetry (in electronic RT-DICOM format) will be requested for all enrolled patients.

Study measures will be available in both English and French. HRQOL measures will include: the Pediatric Quality of Life (PedsQL) General module; the PedsQL Brain Tumour module; the PedsQL Family Impact module; and the Short Form 36 (SF-36), to assess parent quality of life via physical and mental health functioning subscales. Children who require help completing questionnaires will be aided by a CRA. For those 2 to 5 years of age or those who have cognitive disability that impairs their ability to self-report as assessed by their parents, proxy-report by parent or caregiver will be used.

The Symptom Screening in Pediatrics Tool (SSPedi) will also be used to screen for pediatric cancer symptoms.

The Patient Reported Outcomes Measurement Information System (PROMIS) Anxiety, Depressive Symptoms, and Pain Interference measures short forms will be administered to screen for current symptoms of anxiety, depression and assess pain interference.

A linear mixed models approach will be used to compare HRQOL outcomes over time. Further, HRQOL outcomes will be compared across assessment time points and paired sample t-tests will be conducted to identify critical periods of significantly lower and/or higher HRQOL for patients and caregivers. Correlational analyses will be used to explore variables that might emerge as related to HRQL outcome scores. Recruitment rates (patients participating vs. patients eligible) and retention rates (non-completion, lost to follow-up) will be examined. Finally, all incident cases of radiation necrosis without obvious tumour progression will be examined, while accounting for competing risks of disease progression and death from any cause.

Eligibility criteria: Inclusion Criteria:

1. Patient aged \>2 and \<21 years treated with a repeat course of radiation for DIPG or other recurrent or progressive brain tumour.
2. Radiation for the first tumour must be a primary brain neoplasm (i.e. not leukemia).
3. Enrollment within 14 days of starting re-irradiation (RT2).
4. Patients with malignant transformation of the first tumour are eligible.
5. There are no restrictions on histology or RT1/RT2 dose-fractionation or RT2 body site. In other words, RT2 may be directed at a different location to RT1.
6. The patient is treated at a site where the study is approved by the local ethics board
7. Consent, and, if applicable, assent, has been obtained according to institutional standards

Exclusion Criteria:

1. Inability to complete questionnaires in English or French.

Primary outcomes:
measure: Health-related quality of life (HRQOL) for children diagnosed with DIPG and in children treated with re-irradiation for a recurrent brain tumour
timeFrame: 2 months after the second radiation
Secondary outcomes:
measure: HRQOL disease specific modules and family impact
timeFrame: 2 months after the second radiation]
measure: Symptom burden for children diagnosed with DIPG and in children treated with re-irradiation for a recurrent brain tumour
timeFrame: 2 months after the second radiation]
measure: Caregiver HRQOL
timeFrame: 2 months after the second radiation]
measure: Anxiety, Depression and Pain Interference
timeFrame: 2 months after the second radiation]
measure: Radiation necrosis (RN), local control, progression-free survival and overall survival after re-irradiation.
timeFrame: 12 months
Other outcomes:
measure: Feasibility of conducting routine assessment of HRQOL in children diagnosed with DIPG/recurrent brain tumours and their caregivers.
timeFrame: 4 months after the second radiation
Locations:
city: Calgary
country: Canada
facility: Alberta Children's Hospital
state: Alberta
city: Edmonton
country: Canada
facility: Stollery Children's Hospital
state: Alberta
city: Vancouver
country: Canada
facility: British Columbia Children's Hospital
state: British Columbia
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Halifax
country: Canada
facility: IWK Health Centre
state: Nova Scotia
city: Hamilton
country: Canada
facility: McMaster Children's Hospital
state: Ontario
city: London
country: Canada
facility: Children's Hospital
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: Children's Hospital of Eastern Ontario
state: Ontario
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Montréal
country: Canada
facility: Centre hospitalier de l'Université de Montréal
state: Quebec
city: Quebec
country: Canada
facility: CHU de Quebec-Universite Laval
Study officials:
affiliation: University of Calgary
name: Fiona Schulte, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Princess Margaret Cancer Centre
name: Derek Tsang, MD
role: PRINCIPAL_INVESTIGATOR
References: