HRQL and Symptom Assessment for Patients With DIPG or Recurrent and Re-irradiated Brain Tumours and Their Caregivers

• ClinicalTrials.gov Identifier: NCT04670016
• Recruitment Status: Recruiting
• First Posted: December 17, 2020
• Last Update Posted: November 10, 2022
• Sponsor: University of Calgary
• Collaborators: University of Toronto; Université de Montréal; University of Ottawa; Western University, Canada; McMaster University; Alberta Children's Hospital; Stollery Children's Hospital; British Columbia Children's Hospital; CancerCare Manitoba; Children's Hospital of Eastern Ontario; The Hospital for Sick Children; McMaster Children's Hospital; Children's Hospital Medical Center, Cincinnati; St. Justine's Hospital; Montreal Children's Hospital of the MUHC; IWK Health Centre; Janeway Children's Health and Rehabilitation Centre; Princess Margaret Hospital, Canada; London Health Sciences Centre; The Ottawa Hospital; CHU de Quebec-Universite Laval
• Information provided by (Responsible Party): Fiona Simone Maria Schulte, University of Calgary

Study Description

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.

Condition or disease	Intervention/treatment
DIPG; Brain Tumor, Pediatric, Recurrent; Brain Tumor, DIPG; Radiation Toxicity; Radiation Exposure; Brain Tumor, Pediatric	Other: This study does not include an intervention.

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.

Study Design

• Study Type: Observational [Patient Registry]
• Estimated Enrollment: 57 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Target Follow-Up Duration: 1 Year
• 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
• Actual Study Start Date: July 2, 2020
• Estimated Primary Completion Date: July 2023
• Estimated Study Completion Date: December 2023

Groups and Cohorts

Group/Cohort	Intervention/treatment
Patient/Caregiver dyad diagnosed with DIPG; All of these criteria must be met for a patient to be eligible for this study: Patient aged >2 and <21 years treated with a repeat course of radiation for DIPG; Radiation for the first tumour must be a primary brain neoplasm (i.e. not leukemia).; Enrollment within 14 days of starting re-irradiation (RT2).; Patients with malignant transformation of the first tumour are eligible.; 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.; The patient is treated at a site where the study is approved by the local ethics board; Consent, and, if applicable, assent, has been obtained according to institutional standards	Other: This study does not include an intervention.; This study does not include an intervention.
Patient/Caregiver dyad with re-RT for a recurrent brain tumour; All of these criteria must be met for a patient to be eligible for this study: Patient aged >2 and <21 years treated with a repeat course of radiation for a recurrent or progressive brain tumour (stratum 2).; Radiation for the first tumour must be a primary brain neoplasm (i.e. not leukemia).; Enrollment within 14 days of starting re-irradiation (RT2).; Patients with malignant transformation of the first tumour are eligible.; 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.; The patient is treated at a site where the study is approved by the local ethics board; Consent, and, if applicable, assent, has been obtained according to institutional standards	Other: This study does not include an intervention.; This study does not include an intervention.

Outcome Measures

Primary Outcome Measures :

1. Health-related quality of life (HRQOL) for children diagnosed with DIPG and in children treated with re-irradiation for a recurrent brain tumour [ Time Frame: 2 months after the second radiation ]
   Health-related quality-of-life will be measured using the Pediatric Quality of Life Inventory (PedsQL) General Core Scales

Secondary Outcome Measures :

1. HRQOL disease specific modules and family impact [ Time Frame: 2 months after the second radiation] ]
   PedsQL Brain Tumor and Family Impact Module
2. Symptom burden for children diagnosed with DIPG and in children treated with re-irradiation for a recurrent brain tumour [ Time Frame: 2 months after the second radiation] ]
   Symptom Screening in Pediatrics (SSPEDI)
3. Caregiver HRQOL [ Time Frame: 2 months after the second radiation] ]
   Short Form 36 (SF-36)
4. Anxiety, Depression and Pain Interference [ Time Frame: 2 months after the second radiation] ]
   Patient Reported Outcomes Measurement Information System (PROMIS): Anxiety, Depression and Pain Interference Short Forms
5. Radiation necrosis (RN), local control, progression-free survival and overall survival after re-irradiation. [ Time Frame: 12 months ]
   Radiation necrosis without obvious tumour progression

Other Outcome Measures:

1. Feasibility of conducting routine assessment of HRQOL in children diagnosed with DIPG/recurrent brain tumours and their caregivers. [ Time Frame: 4 months after the second radiation ]
   Recruitment (patients participating vs. patients eligible) and retention rates

Eligibility Criteria

• Ages Eligible for Study: 2 Years to 21 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• 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.

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.

Contacts and Locations

Contacts

Contact: Caitlin Forbes; 403-955-7831; caitlin.forbes@ucalgary.ca

Locations

Canada, Alberta

Alberta Children's Hospital; Recruiting

Calgary, Alberta, Canada, T3B 6A8

Contact: Caitlin Forbes 403-955-7831 caitlin.forbes@albertahealthservices.ca

Principal Investigator: Fiona Schulte, PhD

Principal Investigator: Douglas Strother, MD

Stollery Children's Hospital; Not yet recruiting

Edmonton, Alberta, Canada, T6G 2B7

Contact: David Eisenstat, MD eisensta@ualberta.ca

Principal Investigator: David Eisenstat, MD

Canada, British Columbia

British Columbia Children's Hospital; Not yet recruiting

Vancouver, British Columbia, Canada, V6H 3N1

Contact: Juliette Hukin, MB jhukin@cw.bc.ca

Principal Investigator: Juliette Hukin, MB

Principal Investigator: Karen Goddard, MD

Canada, Manitoba

CancerCare Manitoba; Not yet recruiting

Winnipeg, Manitoba, Canada, R3E 0V9

Contact: Magimairajan Issai Vanan, MD MagimairajanIssai.Vanan@cancercare.mb.ca

Principal Investigator: Magimairajan Issai Vanan, MD

Principal Investigator: Junliang Liu, MD

Canada, Nova Scotia

IWK Health Centre; Recruiting

Halifax, Nova Scotia, Canada, B3K 6R8

Contact: Craig Erker, MD craig.erker@iwk.nshealth.ca

Principal Investigator: Craig Erker, MD

Canada, Ontario

McMaster Children's Hospital; Recruiting

Hamilton, Ontario, Canada, L8N 3Z5

Contact: Adam Fleming, MD afleming@mcmaster.ca

Principal Investigator: Adam Fleming, MD

Principal Investigator: Ian Hodson, MD

Children's Hospital; Not yet recruiting

London, Ontario, Canada, N6A 5W9

Contact: Shayna Zelcer, MD shayna.zelcer@lhsc.on.ca

Principal Investigator: Shayna Zelcer, MD

Principal Investigator: Tracy Sexton, MD, PhD

London Health Sciences Centre; Not yet recruiting

London, Ontario, Canada, N6A 5W9

Contact: Glenn Bauman, MD glenn.bauman@lhsc.on.ca

Principal Investigator: Glenn Bauman, MD

Children's Hospital of Eastern Ontario; Recruiting

Ottawa, Ontario, Canada, K1H 8L1

Contact: Donna Johnston, MD djohnston@cheo.on.ca

Principal Investigator: Donna Johnston, MD

Principal Investigator: Asha Nair, MD

Principal Investigator: Lynn Chang, MD

The Hospital for Sick Children; Recruiting

Toronto, Ontario, Canada, M5G 1X8

Contact: Ute Bartels, MD, MSc ute.bartels@sickkids.ca

Principal Investigator: Ute Bartels, MD, MSc

Principal Investigator: Eric Bouffet, MD

Principal Investigator: Vijay Ramaswamy, MD, PhD

Principal Investigator: Lillian Sung, MD, PhD

Princess Margaret Cancer Centre; Not yet recruiting

Toronto, Ontario, Canada, M5G 2M9

Contact: Derek Tsang, MD, MSc derek.tsang@rmp.uhn.ca

Principal Investigator: Derek Tsang, MD, MSc

Principal Investigator: Amy Zhihui Liu, PhD

Principal Investigator: David Hodgson, MD, MPH

Principal Investigator: Normand Laperriere, MD

Canada, Quebec

Centre hospitalier de l'Université de Montréal; Not yet recruiting

Montréal, Quebec, Canada, H3T 1C5

Contact: Anne-Marie Charpentier, MD anne-marie.charpentier@umontreal.ca

Principal Investigator: Anne-Marie Charpentier, MD

Canada

CHU de Quebec-Universite Laval; Recruiting

Quebec, Canada, G1V 4G2

Contact: Valérie Larouche, MD valerie.larouche@chudequebec.ca

Principal Investigator: Valérie Larouche, MD

Sponsors and Collaborators

University of Calgary

University of Toronto

Université de Montréal

University of Ottawa

Western University, Canada

McMaster University

Alberta Children's Hospital

Stollery Children's Hospital

British Columbia Children's Hospital

CancerCare Manitoba

Children's Hospital of Eastern Ontario

The Hospital for Sick Children

McMaster Children's Hospital

Children's Hospital Medical Center, Cincinnati

St. Justine's Hospital

Montreal Children's Hospital of the MUHC

IWK Health Centre

Janeway Children's Health and Rehabilitation Centre

Princess Margaret Hospital, Canada

London Health Sciences Centre

The Ottawa Hospital

CHU de Quebec-Universite Laval

Investigators

• Principal Investigator: Fiona Schulte, PhD; University of Calgary
• Principal Investigator: Derek Tsang, MD; Princess Margaret Cancer Centre

More Information

• Responsible Party: Fiona Simone Maria Schulte, ssistant Professor in the Department of Oncology, Division of Psychosocial Oncology in the Cumming School of Medicine, University of Calgary
• ClinicalTrials.gov Identifier: NCT04670016
• Other Study ID Numbers: HREBA.CC-16-0821
• First Posted: December 17, 2020
• Last Update Posted: November 10, 2022
• Last Verified: November 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Fiona Simone Maria Schulte, University of Calgary:

health-related quality of life; psychosocial; re-irradiation; DIPG; pediatric brain tumor

Additional relevant MeSH terms:

Neoplasms; Brain Neoplasms; Diffuse Intrinsic Pontine Glioma; Recurrence; Disease Attributes; Pathologic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Stem Neoplasms; Infratentorial Neoplasms