Compliance with dietary guidelines and its relationship with symptoms and clinical outcomes in patients with advanced cancer in early-phase oncology clinical trials.

199 Background: We examined compliance with the Dietary Guidelines for Americans and its association with symptom burden and clinical outcomes in patients with advanced cancer in early-phase clinical trials testing novel immunotherapeutic and targeted agents. Methods: Patients starting an early-phase clinical trial (ECOG-PS = 0-1) were recruited into a prospective, longitudinal design with assessments at baseline and at the end of Cycle 1. Diet and symptom burden were assessed using the validated National Cancer Institute Diet History Questionnaire (NCI-DHQ) and the MD Anderson Symptom Inventory, respectively. Compliance with the Dietary Guidelines for Americans recommendations was measured via the Healthy Eating Index (HEI) (a measure of dietary intake per total energy), computed from NCI-DHQ food group and nutrient scores; higher HEI scores indicate greater compliance with dietary guidance recommendations (possible range = 0–100). Statistical tests included Spearman rank correlations (rho), and Cox proportional hazards models. Results: Among early-phase clinical trial patients [N = 40; 50% female; 80% Non-Hispanic White; 80% ECOG = 1; 36% on trials including an immunotherapeutic agent and 64% on targeted therapy trials; mean age = 55y; mean BMI = 28], mean HEI was 69, compared to 59 for the US general population. The proportion of phase I clinical trial patients who met adequacy guidelines were 80% for whole fruit, 73% for total protein foods, 55% for seafood and plant proteins, 55% for total fruit, 50% for greens and beans, 28% for total vegetables, 15% for fatty acids [(PUFAs + MUFAs)/SFAs ≥2.5], 13% for dairy, and 0% for whole grains. The proportion of patients who met moderation guidelines were 28% for refined grains, 28% for added sugar, 13% for saturated fat, and 0% for sodium. Female patients had higher HEI scores than male patients (73 vs. 65, P = 0.004). Patients who were normal weight (BMI < 25) had higher scores for meeting the moderation in sugar intake guideline than overweight patients (BMI≥25) (7.7 vs. 5.5, P = 0.031). Higher intakes of cooked lean meat from beef, pork, veal, lamb, and game were linked to prolonged overall survival (HR = 0.5, 95%CI = 0.26, 0.96, P = 0.039). In immunotherapy patients, greater compliance with seafood and plant protein recommendations was associated with less fatigue at end of Cycle 1 (rho = -0.7, P = 0.008); in targeted therapy patients, higher glycemic load was associated with worse pain (rho = 0.7, P = 0.004). Conclusions: Diets of these early-phase clinical trial patients overall were congruent with recommendations in the Dietary Guidelines for Americans. However, increasing intakes of whole grains and reducing sodium intakes may be useful dietary goals for this population. Also, dietary factors may influence symptoms, such as fatigue and pain, in early-phase clinical trial patients with advanced cancer.

Application of a Cloud Video Conference Method for Recruiting Healthy Subjects Into an Early-Phase Clinical Trial During the COVID-19 Pandemic

Objective: Our objective is to explore the effect of applying cloud video conferencing methods to the informed consent process in an early-phase clinical trial during the COVID-19 pandemic.Methods: All participants who intended to participate in the trial were informed via a cloud video conference before signing the informed consent forms (ICF). Then, the attitudes of the participants with the cloud video conference and their understanding of the trial were evaluated using a questionnaire when they visited to sign the ICF onsite.Results: A total of 165 subjects participated in the cloud video conference process, and 142 visited the site to sign and date the ICFs at the center during the appointment time. The survey showed that nearly 100% of the subjects evaluated the video-based informed consent process as very good or good and gave correct answers to questions about the trial. Furthermore, 136 (95.8%) subjects believed that the knowledge about the trial derived via the video-based informed consent process was consistent with the onsite reality, and 139 (97.9%) subjects expressed their willingness to participate in an informed consent procedure undertaken through an online video conference.Conclusions: The video-based informed consent process achieved the same effects as an onsite informed consent process. The former saves time and cost of transportation for the subject and exhibits good public acceptance; especially in light of the COVID-19 pandemic, this process is conducive for reducing the risk of subject infection due to travel and would also help avoid crowding on site.

Psilocybin: From Serendipity to Credibility?

Psilocybin has a long history of non-medical use and some seem to infer from this that it has therapeutic utility. Early phase clinical trials with psilocybin are encouraging, but suggest only that larger, multicentre trials are required. These are ongoing but will take many years to complete. Meanwhile, retreat centers offering paid experiences with psilocybin truffles have opened in some countries, often using early phase clinical trial data as a basis for bold, public facing claims. This seems unwise. Early phase trials are not designed for their results to be generalized outside the setting they were undertaken in. To do so risks being misleading. Providing what may be seen as an unregulated drug intervention as a paid service is difficult to reconcile with long-held ethical principles underpinning human research and treatment development that were laid down by the 1947 Nuremberg Code and the 1962 Kefauver Harris Amendments. By using psilocybin before it has been properly tested, retreat centers may be undermining their own credibility and the credibility of the wider field.

A Bayesian Zero-Inflated Binomial Regression and Its Application in Dose-Finding Study

In early phase clinical trial, finding maximum-tolerated dose (MTD) is a very important goal. Many researches show that finding a correct MTD can improve drug efficacy and safety significantly. Usually, dose-finding trials start from very low doses, so in many cases, more than 50% patients or cohorts do not have dose-limiting toxicity (DLT), but DLT may occur suddenly and increase fast along with just two or three doses. Although some fantastic models were built to find MTD, little consideration was given to those ‘0 DLTs’ and the ‘jump’ of DLTs. We developed a Bayesian zero-inflated binomial regression for dose-finding study based on Hall (2000), which analyses dose-finding data from two aspects: 1) observation of only zeros, 2) number of DLTs based on binomial distribution, so it can help us analyse if the cohorts without DLT have potential possibility to have DLT and fit the ‘jump’ of DLTs.

Effective targeted antitumor activity of the antimicrobial agent taurolidine against relapsed/refractory neuroblastoma: Cytotoxicity, target modulation and tumor xenograft studies.

e21502 Background: Neuroblastoma (NB) is the most common extracranial solid tumor and one of the most complex and difficult to treat diseases in pediatrics. Currently, even with highly aggressive treatment protocols, the prognosis for patients with high-risk and relapsed NB remains poor. Hence, there is a clear need to identify new agents and novel therapeutic strategies for the treatment of these children. Taurolidine (TRD) is derived from the aminosulfoacid taurine and has known anti-microbial and anti-inflammatory properties. TRD has demonstrated anti-neoplastic activity against a range of aggressive human tumors. We present mechanistic evidence and supportive preclinical data from in vitro and animal models of refractory NB for the development of an early phase clinical trial incorporating TRD. Methods: For in vitro activity studies, a panel of cell lines derived from patients with relapsed NB (n = 6) and normal control cells were treated with increasing concentrations of TRD and cell viability was measured by alamar blue assay. Phase-contrast light microscopy, western blotting, time-lapse video microscopy and analysis of global gene expression by RNA-Seq were used to evaluate target modulation and induction of cell death pathways. Bioluminescence imaging of mice bearing NB xenografts treated with TRD was used to investigate the efficacy of TRD in vivo. Results: Cell survival data showed that TRD is cytotoxic against NB cell lines in vitro (mean IC50 value 100 µM, range 65-135 µM). Phase-contrast and time-lapse video microscopy confirmed the antitumor effects of TRD. Western blot analyses identified that TRD induced target modulation and an effective apoptotic cascade, resulting in PARP cleavage. Gene expression analyses and signaling pathway activation scores indicated alterations in the Notch, MAPK and IL-10 signaling pathways. Xenograft studies further validated the in vivo activity of TRD with decreased tumor burden in treated mice and a measurable improvement in survival. Conclusions: Our study provides key pre-clinical data on the activity and mechanism of action of TRD against NB. The findings support the rationale for further evaluation of TRD for the treatment of relapsed/refractory NB patients in an early phase clinical trial.