IWK Foundation

10023 Background: There are few therapeutic options for pediatric patients with relapsed or refractory cancers. The impact of early phase trial enrolment on the quality of life (QOL) and symptom burden in this patient population is unknown. We hypothesized that this information could inform future clinical trial design and would be of value to clinicians, patients and their families. The primary aim was to determine if those enrolled on a phase I or II trial had improved QOL measured using the PedsQL 3.0 Acute cancer Module compared to those eligible, not not enrolled on a trial. Methods: In this Canadian multi-site study, we included patients 2-18 years of age who were enrolled on a phase I/II clinical trial and those who would have been eligible but did not enroll. The PedsQL 3.0 Acute Cancer Module was completed at baseline, week 4 and week 8 by guardians and by patients, for those age 5 and older. The PedsQL 3.0 Acute Cancer Module total scores were compared separately for patients and guardians using a mixed linear registration model with a random effect for a patient. Results: Of the 80 patients, 31 (39%) patients were enrolled on an early phase trial and 49 (61%) were not enrolled. The majority of patients had a brain tumor (63.3% of those enrolled; 32.7% of those not), followed by a bone tumor (16.7% of those enrolled; 24.5% of those not). In both groups, the majority of patient were included at the time of their first relapse (64.5% of those enrolled and 69.9% of those not). No significant difference was found between PedsQL3.0 patients or guardians; p = 0.09). The PedsQL3.0 total scores were significantly higher for patients enrolled on an early phase trial compared to those patients not enrolled (p = 0.01). However, after adjusting for baseline levels, the difference between enrolled patients vs not was not statistically significant (p = 0.8). Conclusions: Being enrolled on an early phase trial does not appear to have a negative effect on one's quality of life. The results have also demonstrated that it is feasible to evaluate patients enrolled and not enrolled on early phase trials and compare their symptom experience using the PedsQL 3.0 Acute cancer Module. Continued efforts will focus on more recruitment and using SSPedi to further investigate differences in QOL. This research is supported through C17 Council, Kindred Foundation and the CHEO Research Institute.

Surface-engineered gold nanoparticles have been considered as versatile systems for theranostics applications. Moreover, surface covering or stabilizing agents on gold nanoparticles especially gold nanobipyramids (AuNBPs) provides an extra space for cargo molecules entrapment. However, it is not well studied yet and also the preparation of AuNBPs still remains dependent largely on cetyltrimethylammonium bromide (CTAB), a cytotoxic surfactant. Therefore, the direct use of CTAB stabilized nanoparticles is not recommended for cancer theranostics applications. Herein, we address an approach of dodecyl ethyl dimethylammonium bromide (DMAB) as biocompatible structure directing agent for AuNBPs, which also accommodate anticancer drug doxorubicin (45%), an additional chemotherapeutics agent. Upon near-infrared light (NIR, 808 nm) exposure, engineered AuNBPs exhibit (i) better phototransduction (51 °C) due to NIR absorption ability (650-900 nm), (ii) photo triggered drug release (more than 80%), and (iii) synergistic chemophototherapy for breast cancer cells. Drug release response has been evaluated in tumor microenvironment conditions (84% in acidic pH and 80% at high GSH) due to protonation and high affinity of thiol binding with AuNBPs followed by DMAB replacement. Intracellular glutathione (GSH, 5-7.5 mM) replaces DMAB from AuNBPs, which cause easy aggregation of nanoparticles as corroborated by colorimetric shifts, suggesting their utilization as a molecular sensing probe of early stage cancer biomarkers. Our optimized recipe yield is monodisperse DMAB-AuNBPs with ∼90% purity even at large scales (500 mL volume per batch). DMAB-AuNBPs show better cell viability (more than 90%) across all concentrations (5-500 ug/mL) when directly compared to CTAB-AuNBPs (less than 10%). Our findings show the potential of DMAB-AuNBPs for early stage cancer detection and theranostics applications.

Background: Under the qualification program of the FDA and EMA, we aimed to develop a Patient Reported Outcome (PRO) measure of signs and symptoms for paediatric ulcerative colitis (UC) (i.e. the TUMMY-UC index) for using in trials and clinical practice. We previously selected items to the index via concept elicitation qualitative interviews. Here we report the results of the cognitive evaluation and the final formatting of the index. Trained personnel performed Cognitive debriefing Interviews in Israel, England, Ireland, Canada and the USA with UC children 2–18 years and, in order to develop an Observer Reported Outcome (obsRO) for those ≤8 years, also their caregivers. We compiled contending scales for each item and explored the vocabulary children prefer. Clinical data including disease activity were recorded. Weights were assigned to each item based on ranking of importance on a “1” (least important) to 5 scale. Interviews were performed with 34 children (age 10.6 ± 4 years; 28% with moderate-severe disease and 55% in remission; 83% with extensive disease) and 13 caregivers (age 37 ± 5 years, 23% males). The questions were understood by all children and exact wording and response options of each item were finalised. 88% of children understood the meaning of “last 24-h since this time” as a recall period. Only 3 children (9YO, 9YO, 12YO) had difficulties recalling the last 24-h. The exact response options were amended based on the obtained feedback; all children <11 years preferred the FACES pain item and most adolescents preferred the VAS version, thus both were retained in a composite item. Rank order of the items was rectal bleeding-amount (4.5), rectal bleeding-frequency (4.3), stool frequency (4.2), abdominal pain (4), urgency (3.8), stool consistency (3.7), nocturnal stools (3.5) and weakness (3.2). Reassuringly, the same rank-order was noticed for the children younger than 11 years. Grading of the TUMMY-UC items. In this phase 2B study, the exact wording, response options and weighting of the eight TUMMY-UC items were finalised. An obsRO version of the TUMMY-UC has been developed for the younger children. The TUMMY-UC will be now validated and evaluated for cut-off scores in a phase 3 study.