Supportive oncology care at home intervention for patients with pancreatic cancer.

155 Background: Patients with pancreatic cancer receiving chemotherapy often experience substantial symptoms and high healthcare utilization. We sought to determine the feasibility of delivering a Supportive Oncology Care at Home intervention designed to address the needs of patients receiving treatment for pancreatic cancer. Methods: We prospectively enrolled patients with pancreatic cancer who were participating in a parent trial of neoadjuvant FOLFIRINOX and residing in-state, within 50 miles of our hospital. Patients received the Supportive Oncology Care at Home intervention during neoadjuvant treatment (i.e., up to 4 months). The intervention entailed: 1) remote monitoring of daily patient-reported symptoms, daily vital signs, and weekly body weight; 2) a hospital in the home care model for symptom assessment and management; and 3) structured communication with the oncology team. We defined the intervention as feasible if ≥60% of patients enrolled in the study and ≥60% completed the daily assessments within the first two weeks of enrollment. We tracked numbers of phone calls, emails, and home visits generated by the intervention. We conducted exit interviews with patients, caregivers, and oncology clinicians to assess the acceptability of the intervention. We also compared rates of treatment delays, urgent clinic visits, emergency room (ER) visits, and hospitalizations among those who did (n = 20) and did not (n = 24) receive Supportive Oncology Care at Home from the parent trial. Results: From 1/2019-9/2020, we enrolled 80.8% (21/26) of potentially eligible patients. One patient became ineligible following consent due to moving out-of-state, resulting in 20 participants (median age = 67 years [range 55-77]; 60.0% female). In the first two weeks of enrollment, 65.0% of participants completed all daily assessments. Overall, patients reported 96.1% of daily symptoms, 96.1% of daily vital signs, and 92.5% of weekly body weights. Each participant generated an average of 2.22 phone calls (range 0.62-3.77), 2.96 emails (range 1.50-5.88), and 0.15 home visits (range 0-0.69) per week. During exit interviews, > 80% of patients, caregivers, and clinicians found the intervention to be helpful and convenient, and they reported high satisfaction with the communication among patients, clinicians, and the hospital in the home team. Patients receiving the intervention had lower rates of treatment delays (55.0% v 75.0%), urgent clinic visits (10.0% v 25.0%), ER visits or hospitalizations (45.0% v 62.5%), as well as a lower proportion of days spent in urgent clinic, ER, or hospital (2.7% v 7.8%), compared with those not receiving the intervention who were in the same parent trial. Conclusions: These findings demonstrate the feasibility and acceptability of a Supportive Oncology Care at Home intervention. Future work will investigate the efficacy of this intervention for decreasing healthcare use and improving patient outcomes. Clinical trial information: NCT03798769.

Supportive oncology care at home intervention for patients with pancreatic cancer.

6558 Background: Patients with pancreatic cancer receiving chemotherapy often experience substantial symptoms and high healthcare utilization. We sought to determine the feasibility of delivering a Supportive Oncology Care at Home intervention designed to address the needs of patients receiving treatment for pancreatic cancer. Methods: We prospectively enrolled patients with pancreatic cancer who were participating in a parent trial of neoadjuvant FOLFIRINOX and residing in-state, within 50 miles of our hospital. Patients received the Supportive Oncology Care at Home intervention during neoadjuvant treatment (i.e., up to 4 months). The intervention entailed: 1) remote monitoring of daily patient-reported symptoms, daily vital signs, and weekly body weight; 2) a hospital in the home care model for symptom assessment and management; and 3) structured communication with the oncology team. We defined the intervention as feasible if ≥60% of patients enrolled in the study and ≥60% completed the daily assessments within the first two weeks of enrollment. We tracked numbers of phone calls, emails, and home visits generated by the intervention. We conducted exit interviews with patients, caregivers, and oncology clinicians to assess the acceptability of the intervention. In addition, we compared rates of treatment delays, urgent clinic visits, emergency room (ER) visits, and hospitalizations among those who did (n = 20) and did not (n = 24) receive Supportive Oncology Care at Home from the parent trial. Results: From 1/2019-9/2020, we enrolled 80.8% (21/26) of potentially eligible patients. One patient became ineligible following consent due to moving out-of-state, resulting in 20 participants (median age = 67 years [range 55-77]; 60.0% female). Within the first two weeks of enrollment, 65.0% completed all the daily assessments, with participants reporting 96.1% of daily symptoms, 96.1% of daily vital signs, and 92.5% of weekly body weights. Each participant generated an average of 2.22 phone calls (range 0.62-3.77), 2.96 emails (range 1.50-5.88), and 0.15 home visits (range 0-0.69) per week. During exit interviews, > 80% of patients, caregivers, and clinicians found the intervention to be helpful and convenient, and they reported high satisfaction with the communication among patients, clinicians, and the hospital in the home team. Patients receiving the intervention had lower rates of treatment delays (55.0% v 75.0%), urgent clinic visits (10.0% v 25.0%), ER visits or hospitalizations (45.0% v 62.5%), as well as a lower proportion of days spent in urgent clinic, ER, or hospital (2.7% v 7.8%), compared with those not receiving the intervention who were in the same parent trial. Conclusions: These findings demonstrate the feasibility and acceptability of a Supportive Oncology Care at Home intervention. Future work will investigate the efficacy of this intervention for decreasing healthcare use and improving patient outcomes. Clinical trial information: NCT03798769.

Parent engagement in co-design of clinical trials: the PARENT trial

Evidence generated from partnering with parents to design and conduct research together may be used to refine, adjust, and modify future research approaches. This study aimed to describe the initial approaches to parent engagement in the design of the PARENT trial as well as understand parent perspectives on the acceptability and relevance of the PARENT trial and potential barriers and facilitators to participation.Parents participating in the TARGet Kids! cohort were invited to participate in a focus group, called the PARENT panel, to co-design the PARENT trial. This focus group was conducted to capture diverse individual and collective parents’ experiences. Overall methodological approaches for the PARENT panel were informed by the CIHR Strategy for Patient Oriented Research (SPOR) guiding principles (mutual respect, co-building, inclusiveness, and support) for patient engagement in research, and facilitated through the Knowledge Translation Program in the Li Ka Shing Knowledge Institute at Unity Health Toronto. Using a Nominal Group Technique, the PARENT panel provided feedback on the feasibility, relevance, and acceptability of the proposed intervention. Findings from this work will be used to further refine, adjust, and modify the next iteration of the PARENT trial, which will also serve as an opportunity to discuss the efforts made by researchers to incorporate parent suggestions and what additional steps are required for improved patient engagement.

Mobile Health for Anemia Reduction: Study Protocol for an Entertainment Education-Based Dual Intervention (Preprint)

BACKGROUND More than half of women of reproductive age (15-49 years old) are anemic in India. Uptake of and adherence to iron folic acid supplements remain low despite sustained efforts to increase use. With India’s burgeoning digital environment, mobile phones offer a potential medium to increase uptake, especially when combined with interactive voice-messages that deliver entertaining stories infused with norms-based educational messages. OBJECTIVE This study investigates whether a norms-based entertainment education mHealth intervention can increase self-efficacy for iron folic acid adherence among women of reproductive age in Odisha, India. mRANI is a randomized two-arm study that includes assessments before and after the intervention. METHODS All study participants are recruited from only the intervention arm of the parent RANI trial. Whereas the usual practice is to randomize participants either to a treatment arm or to a usual-care control arm, we are assigning the mRANI control group to another entertainment education-based treatment group – one designed to improve bystander intervention to reduce violence against women. Data collection for mRANI is embedded in the parent trial and will include baseline and end-line assessments. Primary outcomes are self-efficacy for iron folic acid adherence and violence against women-related bystander intervention. Inclusion criteria for mRANI is participation in the parent trial and phone ownership. Women (approximate n = 400) who meet mRANI inclusion criteria will be randomly assigned to the IFA arm or the bystander arm. Ordinary least squares regression with robust standard errors will be conducted to assess between-group comparisons at end-line. A mediation analysis will examine whether social norms and interactivity mediate the relationship between intervention exposure and primary outcomes in both arms. Real-time monitoring data will offer insights into intervention receptivity and audience engagement. RESULTS This study will provide evidence on whether an mHealth norms-based entertainment education intervention can increase self-efficacy for iron folic acid adherence and violence against women-related bystander intervention. CONCLUSIONS mRANI may provide an efficient and digital medium to reduce anemia and violence against women in an increasingly digital and socially distanced world owing to COVID-19. CLINICALTRIAL The parent trial (RANI) was registered with Clinical Trial Registry- India (CTRI) (CTRI/2018/10/016186) on 29 October 2018.

Seven-step framework to enhance practitioner explanations and parental understandings of research without prior consent in paediatric emergency and critical care trials

BackgroundAlternatives to prospective informed consent enable the conduct of paediatric emergency and critical care trials. Research without prior consent (RWPC) involves practitioners approaching parents after an intervention has been given and seeking consent for their child to continue in the trial. As part of an embedded study in the ‘Emergency treatment with Levetiracetam or Phenytoin in Status Epilepticus in children’ (EcLiPSE) trial, we explored how practitioners described the trial and RWPC during recruitment discussions, and how well this information was understood by parents. We aimed to develop a framework to assist trial conversations in future paediatric emergency and critical care trials using RWPC.MethodsQualitative methods embedded within the EcLiPSE trial processes, including audiorecorded practitioner–parent trial discussions and telephone interviews with parents. We analysed data using thematic analysis, drawing on the Realpe et al (2016) model for recruitment to trials.ResultsWe analysed 76 recorded trial discussions and conducted 30 parent telephone interviews. For 19 parents, we had recorded trial discussion and interview data, which were matched for analysis. Parental understanding of the EcLiPSE trial was enhanced when practitioners: provided a comprehensive description of trial aims; explained the reasons for RWPC; discussed uncertainty about which intervention was best; provided a balanced description of trial intervention; provided a clear explanation about randomisation and provided an opportunity for questions. We present a seven-step framework to assist recruitment practice in trials involving RWPC.ConclusionThis study provides a framework to enhance recruitment practice and parental understanding in paediatric emergency and critical care trials involving RWPC. Further testing of this framework is required.

Effects of Zinc Alone versus Zinc-Containing Multiple Micronutrient Powder on Insulin-Like Growth Factor 1 (IGF1) and IGF Binding Protein-3 (IGFBP3) in Laotian Children (OR07-05-19)

Objectives To assess a) the impact of daily preventive zinc tablets (7 mg; PZ), multiple micronutrient powder (10 mg zinc, 6 mg iron and 13 other micronutrients; MNP) or placebo on Insulin-like Growth Factor 1 (IGF1), IGF Binding Protein 3 (IGFBP3) and IGF1 bioavailability (indexed by molar IGF1: IGFBP3 ratio), among Laotian children aged 6–23 mo; b) potential effect modification by baseline physical growth status. Methods Plasma samples from 419 children participating in the parent trial (n = 3407) were collected at baseline and after ∼9 mo (endline). Determination of IGF1 and IGFBP3 were done via an automated chemiluminescent assay. Linear regression models were used to assess main and modifying effects of PZ and MNP on IGF1 and IGFBP3, controlling for age, sex, district and baseline values of each biomarker. Results The parent trial found no overall treatment effects on physical growth. In this subgroup, mean age at baseline was 14.2 ± 5.1 mo and ∼38% were stunted. IGF1 and IGFBP3 at baseline were 45.9 ng/ml and 2143.0 ng/ml, respectively. At endline, geometric mean IGF1 (∼39.0–39.2 ng/ml; P = 0.99), IGFBP3 (2038–2076 ng/ml; P = 0.83) and molar IGF1: IGFBP3 ratio (0.071–0.073; P = 0.74) did not differ by group. Baseline weight-for-age z-score (WAZ) modified the treatment effect on IGFBP3 (p for interaction = 0.05) and molar IGF1: IGFBP3 (p for interaction = 0.04). In non-underweight children (WAZ ≥ -2), mean IGFBP3 in the PZ group (2000 ng/ml) was significantly lower than in the placebo (2148 ng/ml; P = 0.03) and MNP (2157 ng/ml; P = 0.03) groups. In underweight children, however, the IGFBP3 in the PZ group (2039 ng/ml) was higher than the placebo (1774 ng/ml; P = 0.05) but not the MNP (1881 ng/ml; P = 0.15) group. PZ (relative to placebo and MNP) appeared to reduce the bioavailability of IGF1 in underweight children, while increasing IGF1 bioavailability in non-underweight children (p interaction = 0.04). Conclusions IGF1 in this population did not respond to PZ or MNP. PZ (relative to placebo and MNP) was associated with higher endline IGFBP3 concentrations in underweight children but lower values in non-underweight children. These results suggest that PZ affected activity in the GH-IGF axis in these children, but additional evidence is needed to understand long term implications for growth in this population. Funding Sources By The Thrasher Research Fund, with support from the Mathile Institute for the Advancement of Human Nutrition, Nutrition International and the Bill & Melinda Gates Foundation.

Impact of Preventive and Therapeutic Zinc Supplements on Citrulline Concentration and the kynurenine: tryptophan Ratio Among Lao Children: A Randomized Controlled Trial (OR07-02-19)

Objectives To investigate the impact of different forms of zinc supplementation on plasma citrulline (CIT), kynurenine (KYN) and tryptophan (TRP) concentrations and the kynurenine: tryptophan ratio (KTR), considered as markers of intestinal function and systemic inflammatory response, among young Lao children. Methods In a randomized controlled double-blind trial, 3407 children aged 6–23 mo were randomized into one of four groups and followed for ∼36 weeks: daily preventive zinc dispersible tablet (7 mg zinc; PZ), daily multiple micronutrient powder (10 mg zinc, 6 mg iron and 13 other micronutrients; MNP), therapeutic zinc supplements for the treatment of diarrhea (20 mg/d for 10 days with each diarrhea episode; TZ), or daily placebo powder (Control). Plasma samples at baseline and endline for 359 children participating in the parent trial were analyzed at the NIH West Coast Metabolomics Center (UC Davis); plasma CIT, KYN and TRP concentrations were determined by hydrophilic interaction chromatography (HILIC) quadrupole time of flight mass spectrometer (QTOF) tandem mass spectrometry (MS/MS). Linear regression models were used to assess the treatment effect, controlling for baseline value, child age and district. Results The parent trial found no overall group-wise effects on linear growth or diarrhea outcomes. In the subgroup included in the present analyses, mean age at enrollment was 16.0 ± 4.9 mo, 37% were stunted and 83% were zinc deficient. At baseline, mean plasma CIT, KYN and TRP concentrations were 24.6 ± 5.4 µM, 3.27 ± 0.83 µM and 72.3 ± 12.9 µM, respectively; the mean KT ratio was 0.046 ± 0.013. 5% of children had low CIT (< 17 µM) and no children had low TRP (< 35 µM). At endline, there were no differences among intervention groups in mean plasma CIT (25.0–26.6 µM, P = 0.287), KYN (2.96–3.11 µM, P = 0.115), TRP (66.1–70.0 µM, P = 0.151) or the KTR (0.046–0.047, P = 0.981). Conclusions In this population, PZ, MNP and TZ had no overall effect on plasma concentrations of CIT, KYN, TRP and the KTR. We plan to further explore if these markers of intestinal function were predictive of subsequent linear growth, or modified the growth response to supplementation. Funding Sources The Bill & Melinda Gates Foundation, Nutrition International and the Mathile Institute for the Advancement of Human Nutrition.

Does antenatal micronutrient supplementation improve children’s cognitive function? Evidence from the follow-up of a double-blind randomised controlled trial in Nepal

IntroductionMultiple Micronutrient (MMN) supplementation during pregnancy can decrease the proportion of infants born low birth weight and small for gestational age. Supplementation could also enhance children’s cognitive function by improving access to key nutrients during fetal brain development and increasing birth weight, especially in areas where undernutrition is common. We tested the hypothesis that children whose mothers received MMN supplementation during pregnancy would have higher intelligence in early adolescence compared with those receiving Iron and Folic Acid (IFA) only.MethodsWe followed up children in Nepal, whose mothers took part in a double-blind Randomised Controlled Trial (RCT) that compared the effects on birth weight and gestational duration of antenatal MMN versus IFA supplementation. We assessed children’s Full Scale Intelligence Quotient (FSIQ) using the Universal Non-verbal Intelligence Test (UNIT), and their executive function using the counting Stroop test. The parent trial was registered as ISRCTN88625934.ResultsWe identified 813 (76%) of the 1069 children whose mothers took part in the parent trial. We found no differences in FSIQ at 12 years between MMN and IFA groups (absolute difference in means (diff): 1.25, 95% CI −0.57 to 3.06). Similarly, there were no differences in mean UNIT memory (diff: 1.41, 95% CI −0.48 to 3.30), reasoning (diff: 1.17, 95% CI −0.72 to 3.06), symbolic (diff: 0.97, 95% CI −0.67 to 2.60) or non-symbolic quotients (diff: 1.39, 95% CI −0.60 to 3.38).ConclusionOur follow-up of a double-blind RCT in Nepal found no evidence of benefit from antenatal MMN compared with IFA for children’s overall intelligence and executive function at 12 years.

Outcomes of Patients with Chronic Lymphocytic Leukemia (CLL) after Idelalisib Therapy Discontinuation

Objective Idelalisib is a first-in-class oral PI3Kd inhibitor approved for use in combination with rituximab in patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL). We describe the characteristics, causes of discontinuation, and outcomes in patients who discontinued treatment after idelalisib therapy. Methods 38 R/R CLL patients participated in 5 idelalisib combination trials at the North Shore-LIJ Cancer Institute and were included in this analysis. The patients were enrolled from 2011 until 2014, and data were locked in March 1st, 2015. Patients were evaluated for time to therapy discontinuation and reasons for discontinuation. The majority of the patients had been heavily pretreated and 39% of the patients had a high risk prognostic marker including deletion of 11q or 17p. 21 R/R CLL patients participated in the Phase Ib trial of idelalisib in combination with several agents including Rituximab (R), Bendamustine (B) ± R, Fludarabine, Chlorambucil ± R, and Ofatumumab. The trial was designed for 48 weeks and patients were allowed to continue on an extension trial with idelalisib if still deriving benefit. Patients on the parent trial were on therapy a median of 335 days. 42% (11/21) continued in the extension trial at the end of the parent trial. Causes of discontinuation from initial 48-week trial included: grade 4 transaminitis (1) on day 64 with failed rechallenge at lower doses; Richter's transformation (1) on day 161; grade 3/4 diarrhea/colitis (4) on days 52, 231, 255, and 365; refractory/progressive CLL (2) on days 8 and 170; aplastic anemia (1) on day 172; and septic shock in a patient with uncontrolled autoimmune hemolytic anemia (1) on day 271. Of the patients on the extension trial, the median time on drug was 412 days with 27% (3/11) discontinuing due to grade 3/4 diarrhea/colitis; 36% (4/11) due to progression, 9% (1/11) due to pneumonia and subsequent progression 2 months later. Of the 3 patients that remain on study, their median time on therapy is 1072 days without evidence of toxicities. Of the 17 patients that participated in placebo-controlled phase III studies, 11 participated in R +/- idelalisib (study 116) and 6 on BR+/-idelalisib (study 115). Study 116 was unblinded during the trial: 35% (4/11) received idelalisib + R upfront. Of these, only 2 patients (50%) were able to continue on extension study as the other 2 patients developed pneumonitis and were taken off study early. One patient is continues on study at day 1011 whereas the second patient developed progressive multifocal leukoencephalopathy on day 714 and died days after being taken off drug. 86% (6/7) of the remaining patients initially randomized to placebo crossed over to idelalisib at the time of confirmed progression. Of these, 14% (1/6) developed both colitis and later pneumonitis, 14% (1/6) withdrew consent, and 14% (1/6) had progression of disease. For blinded study 115 (BR+/-idelalisib), 6 patients participated: 33% (2/6) developed grade 3/4 diarrhea/colitis, 16% (1/6) developed pneumonitis, and 16% (1/6) has progressed. In our experience, none of the patients with severe diarrhea/colitis were able to maintain lower doses for a prolonged period of time without recurrent colitis or the development of pneumonitis. Since the start of these trials, 31% (12/38) of the patients have died: the overall survival after discontinuation for these patients varies widely from 0 to 303 days with a median overall survival of 64 days after discontinuation. Most patients with relapsed/refractory CLL who discontinued idelalisib early were difficult to treat and had poor outcomes. Over the course of the trials, the Bruton's tyrosine kinase inhibitor ibrutinib was approved and used as salvage therapy in 10 patients with confirmed progression; except for 1 patient, all patients successfully achieved a prolonged response with ibrutinib suggesting salvage therapy with a targeted agent may be a reasonable therapeutic approach for patients after idelalisib failure. Interestingly, the rate of Richter's transformation was extremely rare in this study (2%). Conclusions This single-institution experience with idelalisib identifies baseline factors associated with therapy discontinuation, mainly grade 3/4 diarrhea/colitis and progression of disease as a reason for discontinuation from therapy. Our data suggest the use of ibrutinib may be a reasonable choice in patients after idelalisib failure. Disclosures Barrientos: ASH-AMFDP: Research Funding; Gilead: Research Funding; NIH/NCATS: Research Funding. Off Label Use: idelalisib is approved in combination with rituximab only. I will discuss our experience of idelalisib in combination with other agents.