Research funded 2011-2015

During 2011-2015, KCA had two flagships:


1 – Experimental therapies for high risk cancers failing conventional drugs; and

2 – Improved detection and management of treatment side-effects in the growing child

1 - Development and initiation of early phase clinical trials.

Early phase clinical trials that arose from local pre-clinical research – from this early work, KCA has now established clinical trial centres at Randwick and Westmead:

DIPG autopsies were performed with tumour material successfully harvested in each case. Viable DIPG cells were grown and a high throughput drug screen performed. Ongoing feedback was provided to families about the clinical data collected. Initial results led to the discovery of the activity of a novel compound, CBL0137, in DIPG. A clinical Phase I trial was started to be developed in conjunction with the US Children’s Oncology Group.

Pre-clinical study

A Phase I trial to test the combination of difluromethylornithine (DFMO) and chemotherapy in children with refractory neuroblastoma has been developed by Dr Ziegler in collaboration with Dr Hogarty at Children’s Hospital of Philadelphia. The trial is being run across 12 USA centres, 1 Canadian and at Sydney Children’s Hospital, Randwick. Up to 2015, there were 24 patients enrolled globally. Of the first 13 patients enrolled 9 had a response of either stable disease or better. A Letter of Intent was submitted to Aminex Therapeutics with plans for a follow-up study of DFMO in combination with a polyamine transport inhibitor. The project was refunded in 2016.

Phase I study

The trial opened in 2012 with 8 paediatric patients with brain cancer enrolled. The establishment of an NSG ™ (immunodeficient) mouse colony at the Kids Research transgenic facility and initial engraftment studies of lentivirally-transduced human haematopoietic stem cells as a model in which to test vector function and safety, allowed the MGMT study to continue with increased gene transfer efficiency. The primary outcome tested in this Phase I study (n=7) was the safety and feasibility of infusing gene-modified hematopoietic stem cells (HSCs) in paediatric patients being treated for high-risk brain tumors. Although sustained engraftment of gene-modified cells was not achieved, CD34+ cells were gene modified with efficiencies equivalent to those reported in similar studies and the cell product met predefined quality standards, with no adverse events or toxicities attributable to the cell product infusion. Technical improvements to the gene therapy protocol could result in higher cell doses and more robust engraftment. This project was closed in 2017.

MGMT Clinical Trial

Cell & Gene Therapy – The Development of Lentiviral vectors for use in gene therapy Phase I clinical trials targeting paediatric cancers

The objective for investigators is to develop a reproducible and robust methodology for lentiviral vector production to meet regulatory expectations with respect to efficacy and safety, suitable for clinical use in Phase I trials. The overall goal is to facilitate future participation of Australian children in gene therapy trials aiming to target paediatric cancer.

Gene therapy Phase I clinical trials


This Phase II trial recruited 9 patients and was closed in 2016.

Pre-clinical studies funded by KCA that are moving toward trials:-

Patients with neuroblastoma associated with MYCN and NCYM gene amplification experience a very poor prognosis. Histone H3.3 H3F3A G34 mutations result in N-Myc over-expression and paediatric glioblastoma. BET bromodomain inhibitors are emerging as one of the most promising novel classes of anticancer agents by blocking the BET bromodomain proteins BRD3 and BRD4 from activating transcription of oncogenes such as MYC and MYCN. However, treatment with BET bromodomain inhibitors alone does not result in cancer remission.


Findings to come.

Establishment of patient-derived xenograft (PDX) models for high risk neuroblastoma

The four aims for this project are:

To confirm that xenografts can be established with a high success rate, and to establish a xenograft panel with matching clinical data and matching molecular and phenotypic data.

To determine whether xenografts can be serially passaged in vivo and that their features reproduce that of the primary patient sample

To determine whether xenograft responses to therapy approximate that of the donor patient.

To determine whether actionable drug targets can be identified and tested using xenografts.

Findings to come.

Diffuse Intrinsic Pontine Glioma (DIPG) is the most aggressive of all childhood malignancies. There are no effective treatments and current therapeutic strategies are only palliative, with rapid tumour progression inevitably resulting in early death. CBL0137, a novel anti-cancer compound developed from quinacrine, targets Facilitates Chromatin Transcription (FACT), a chromatin remodelling complex involved in transcription, replication, and DNA repair. CBL0137 effectively crosses the blood brain barrier and is currently in Phase I trial in adults. The aim of this project was (i) to investigate the mechanism of action by which CBL0137 prevents the proliferation of DIPG cells, (ii) to determine optimal combination strategies to enhance the effect of CBL0137 and (iii) to test the activity of CBL0137 in in vivo DIPG models.

Findings to come

2 - Invention and application of novel diagnostics

3 - Improvement of models of care

There has been no agreed model of care for the more than 18,000 Australian CCS who are at risk of specific health problems as a consequence of their successful anti-cancer treatment.

In response to this we 1) evaluated paediatric cancer survivors’ needs, barriers and preferences for the delivery of long-term follow-up care; 2) assessed the feasibility of primary care involvement in long-term follow-up; and 3) evaluated, using a randomised controlled trial, an e-healthcare platform with which survivors, specialists and GPs may manage coordinated survivorship care plans.

Clinicians, parents and patients were surveyed across Australia and New Zealand at 11 participating sites. 523 completed questionnaires were received (82% response rate of contactable participants) of which 76 participants also completed a second, interview, phase of the study. Results suggested many CCS have unmet information needs, report barriers to care, and are not engaged in any cancer-related follow-up care, despite experiencing a large number of health issues. The feasibility of primary care (i.e. general practitioner, GP) involvement in the CCS model of care was assessed by interviewing a national sample of GPs (N=38). Assessment was done using qualitative methods to gain a more in-depth understanding of GPs confidence in caring for cancer survivors. Results suggest GPs lack confidence caring for CCS but are willing to become their primary carers with the right information and support from tertiary services. A randomised controlled trial, an e-healthcare platform with which survivors, specialists and GPs may manage coordinated survivorship care plans by pilot testing three e-tools with health professionals and consumers (N=75), using focus groups, interviews and short questionnaires. Health professionals’ and consumers’ preferences for e-tools was ascertained, including their preferred e-tool.

Primary Care Physicians Perspectives

Models of CCS care in Aus and NZ

Narrative Review of Models of Care

Systematic Review Health care CCS

Recruiting primary care physicians to research – CCS

Dental hygiene in childhood cancer survivors

CCS perceptions for future health and cancer risk

The avatar acceptability study

Why us? Causal attributions

Childhood cancer survivors’ transition to adult care

CCS’ and parents’ information needs

The survivor perspective

CCS genetic testing – consumer attitudes

CCS sleep disturbance

There has been recognition that the needs of adolescent and young adult (AYA) patients with cancer are different from both adults and younger children and warrant specialised services. This study aimed to demonstrate the effectiveness of telehealth in implementing psychosocial support among AYAs with cancer, while also assessing its utility as an age-appropriate model of delivering support, considering AYAs developmental concerns around autonomy and independence. An additional aim was to demonstrate evidence supporting the validity of the AYA Psychosocial Assessment Screening Tool and Psychosocial Assessment. While the tool was widely used and has been validated in numerous adult cancer populations, participants under the age of 18 have been excluded. Thus, there is currently no validated instrument for measuring distress amongst AYAs with cancer. This information will be used to feed into proposals for a larger national representative validation study.

Validation distress thermometer for AYAs with cancer

Delivering CBT using videoconferencing

4 - Application of evidence into practice

This study aimed to identify the preclinical factors that establish biological plausibility and predict the success of early phase clinical trials in paediatric cancer patients. Almost 25% of trials have been categorised as “successful”, where either the authors criteria for success of the trial was achieved, a complete response of 20% or more was observed, or the trials progressed to phase III status. For example, for successful trials, there was more preclinical data to support their initiation. The completed study will for the first time provide robust evidence to help determine what preclinical experiments are required to proceed with early phase clinical trial. The determination of these factors will be of international significance, allow for rationalisation of resources, improve the rational translation of novel therapeutics, reduce the costs of clinical trials, and ultimately improve outcomes for patients with enhanced efficacy and reduced toxicities.

Predictors of phase II paediatric oncology clinical trials

The study aimed to better understand communication, comprehension and decision making occurring for high risk paediatric oncology medical procedures and therapies, including early phase clinical trials and bone marrow transplant. Quantitative and qualitative data was collected to better understand clinician attitudes, referral and communication regarding early phase childhood cancer studies. The plan involved the survey of attitudes of clinicians on care in the relapsed setting including experimental therapies, hope, risk, end of life and palliative care treatment decisions. Investigators observed communication between physicians and parents/patients and assessed the understanding of all parties following this process. A much-improved understanding of legal and regularity frameworks governing access to experimental therapies for paediatric patients was gained.

Healthcare professional’s perspective

A retrospective, longitudinal audit of height and weight in nearly 200 survivors of childhood cancer enrolled on an Acute Lymphoblastic Leukaemia (ALL) treatment at the Sydney Children’s Hospital Randwick was conducted. It was identified that a large proportion (37.88%) of children treated for ALL at Randwick are overweight up to seven years after diagnosis and persisting despite no further corticosteroid use. In response to this, a lifestyle intervention was developed to prevent obesity and metabolic complications in young childhood cancer survivors recently off treatment. The program called Reboot-KIDS was run as a feasibility study in 2016 with a view to developing a randomised controlled trial to examine its effectiveness in improving dietary habits, which included increasing fruit and vegetable intake and reducing non-core (junk) food intake.

Reboot Kids Protocol

Parent feeding interactions