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The purpose of this study was to first characterize the prevalence of recall, recognition, and knowledge of colon cancer screening tests and guidelines (collectively, "awareness") among non-Hispanic black (NHB) and NH white (NHW) urban colon cancer patients. Second, we sought to examine whether awareness was associated with mode of cancer detection. Low awareness regarding colon cancer screening tests and guidelines may explain low screening rates and high prevalence of symptomatic detection. We examined recall, recognition, and knowledge of colorectal cancer (CRC) screening tests and guidelines and their associations with mode of cancer detection (symptomatic versus screen-detected) in 374 newly diagnosed NHB and NHW patients aged 45-79. Patients were asked to name or describe any test to screen for colon cancer (recall); next, they were given descriptions of stool testing and colonoscopy and asked if they recognized each test (recognition). Lastly, patients were asked if they knew the screening guidelines (knowledge). Overall, awareness of CRC screening guidelines was low; just 20% and 13% of patients knew colonoscopy and fecal test guidelines, respectively. Awareness of CRC screening tests and guidelines was especially low among NHB males, socioeconomically disadvantaged individuals, and those diagnosed at public healthcare facilities. Inability to name or recall a single test was associated with reduced screen-detected cancer compared with recall of at least one test (36% vs. 22%, p = 0.01). Low awareness of CRC screening tests is a risk factor for symptomatic detection of colon cancer.

Objectives Insulin-like growth factor-methotrexate (IGF-MTX) is a conjugate of methotrexate and 765IGF, a variant of IGF-1 with high affinity for insulin-like growth factor type 1 receptor. The study aim was to determine the maximum tolerated dose of IGF-MTX in refractory solid organ and hematologic malignancies expressing insulin-like growth factor type 1 receptor. Materials and methods This phase I trial used a modified toxicity probability interval design with 5 cohort dose levels, and expansion cohort at maximum tolerated dose. IGF-MTX was given intravenously over 90 minutes on days 1, 8, and 15 of a 28-day cycle. Results A total of 17 patients were enrolled. The highest tolerated dose tested was 0.80 µEq/kg with dose-limiting toxicity of grade 3 hypoglycemia. Drug-related grade 3 and 4 toxicities included abdominal pain (26%), hypoglycemia (10%), and hypotension (10%). Of the 15 evaluable for response, 3 patients (20%) had stable disease, including the patient with Hodgkin lymphoma with stable disease for 12 cycles of therapy. IGF-MTX concentrations declined rapidly, with half-lives of 5.2 to 14 minutes for the initial distribution phase and 6.5 to 7.5 hours for the terminal elimination phase. Higher IGF-R1 expression did not correlate with better outcome. Conclusions IGF-MTX is well tolerated. IGF-MTX pharmacokinetics suggest rapid cellular uptake. The activity of IGF-MTX in Hodgkin lymphoma should be explored.

Gemcitabine is widely utilized in the treatment of pancreatic, ovarian, and non small cell lung cancers. Gemcitabine is associated with a wide spectrum of lung toxicities, ranging from dyspnea 25% of patients to severe pulmonary toxicity in up to 5% of patients. There is a dearth of information specific to pulmonary toxicity in the setting of gemcitabine combination chemotherapy. Given the potential severity, it is important to identify it early by excluding more common etiologies. We share two case reports of patients with pancreatic cancer who developed severe pulmonary toxicity during gemcitabine combination chemotherapy. Both cases emphasize the heightened risk of pulmonary toxicity in patients receiving gemcitabine chemotherapy combinations, and a need to be vigilant to initiate appropriate therapies immediately.

BackgroundClinical trials establish the standard of care for cancer and other diseases. While social network analysis has been applied to basic sciences, the social component of clinical trial research is not well characterized. We examined the social network of cancer clinical trialists and its dynamic development over more than 70 years, including the roles of subspecialization and gender in relation to traditional and network-based metrics of productivity.MethodsWe conducted a social network analysis of authors publishing chemotherapy-based prospective trials from 1946-2018, based on the curated knowledge base HemOnc.org, examining: 1) network density; 2) modularity; 3) assortativity; 4) betweenness centrality; 5) PageRank; and 6) the proportion of co-authors sharing the same primary cancer subspecialty designation. Individual author impact and productive period were analyzed as a function of gender and subspecialty.FindingsFrom 1946-2018, the network grew to 29,197 authors and 697,084 co-authors. While 99.4% of authors were directly or indirectly connected as of 2018, the network had very few connections and was very siloed by cancer subspecialty. Small numbers of individuals were highly connected and had disproportionate impact (scale-free effects). Women were under-represented and likelier to have lower impact, shorter productive periods (PInterpretationThe network of cancer clinical trialists is best characterized as a strategic or “mixed-motive” network, with cooperative and competitive elements influencing its appearance.Network effects e.g., low centrality, which may limit access to high-profile individuals, likely contribute to ongoing disparities.FundingVanderbilt Initiative for Interdisciplinary Research; National Institutes of Health; National Science FoundationResearch in contextEvidence before this studyWe reviewed the literature on social networks from the 1800’s to 2018. Additionally, MEDLINE was searched for (“Social Networking”[Mesh] OR “Social Network Analysis”) AND (“Clinical Trials as Topic”[Mesh] OR “Hematology”[Mesh] OR “Medical Oncology”[Mesh]) without date restriction. The MEDLINE search yielded 43 results, of which 8 were relevant; none considered gender nor temporality in their analyses. To our knowledge, there has not been any similar study of the dynamic social network of clinical trialists from the inception of the fields of medical oncology and hematology to the present.Added value of this studyThis is the first dynamic social network analysis of cancer clinical trialists. We found that the network was sparse and siloed with a small number of authors having disproportionate impact and influence as measured by network metrics such as PageRank; these metrics have become more disproportionate over time. Women were under-represented and likelier to have lower impact, shorter productive periods, less network centrality, and a greater proportion of co-authors in their same cancer subspecialty.Implications of all the available evidenceWhile gender disparities have been demonstrated in many fields including hematology/oncology, our analysis is the first to show that network factors themselves are significantly implicated in gender disparity. The increasing coalescence of the network by traditional cancer type and around a small number of high-impact individuals implies challenges when the field pivots from traditionally disease-oriented subspecialties to a precision oncology paradigm. New mechanisms are needed to ensure diversity of clinical trialists.

225 Background: The 2018 ASCO Guidelines recommend that physicians document discussions about fertility with all female patients < 49 years old at the time of cancer diagnosis. Patients interested in fertility preservation (FP) should be referred to Reproductive Endocrinology and Infertility (REI) prior to chemotherapy. Retrospective review of oncology patients at our academic medical center over 6 months found that 33% of females < 49 years old had FP discussion documented. We aimed to increase FP discussions and help expedite referrals to REI from 33% to 75% within 5 months. Methods: All new chemotherapy orders were reviewed weekly. Female patients between ages 18-49 were identified and charts were abstracted for the following: age, race, diagnosis, stage, type and line of chemotherapy, and FP discussion. If FP was not discussed, the physician was contacted in real time via email to address FP with the patient and document the discussion. Charts were reviewed 2-4 weeks later to determine if FP was documented. To better understand barriers to FP documentation, fellows and attendings were surveyed to target future interventions. Results: From Dec. 2018 to Apr. 2019, 6/27 (22%) patients had documented discussions of FP. Post intervention, this number increased to 17/27 (63%) with one referral to REI. Intent of chemotherapy was curative in 56% of patients, and 67% were receiving their first line of chemotherapy. 2/15 (13%) patients receiving curative treatment and 4/12 (33%) patients receiving palliative chemotherapy had documentation of FP, both of which increased with intervention to 8/15 (53%) and 9/12 (75%), respectively. Conclusions: Our intervention successfully increased FP discussion from 33% to 63%, but we did not meet our goal of 75%. Per our survey results, the most common barriers to FP discussion were time constraints, inexperience discussing FP, and perception of prohibitive cost to the patient. We are designing our next intervention to address provider inexperience with FP discussion. This will include education regarding the financial aspects of REI and discussion of the new Oncofertility law in Illinois (HB2617), which ensures insurance coverage for oncofertility as of Jan 2019.

Background: PAC-1 is a small molecule that directly activates procaspase-3 and induces apoptosis of cancer cells. PAC-1 crosses the blood-brain-barrier. This first-in-human, phase I, multicenter study consists of 2 components. Component 1 evaluated safety, pharmacokinetics (PK), and preliminary clinical activity of single agent PAC-1 in patients with solid tumors or lymphoma. Component 2 combines PAC-1 with temozolomide in patients with refractory high-grade astrocytomas. Methods: Patients with metastatic solid tumors or lymphomas were enrolled in component 1 and patients with refractory high-grade astrocytomas were enrolled in component 2. A modified- Fibonacci dose-escalation 3+3 design was used in both components. The primary objective was to assess maximum tolerated dose (MTD). In component 1, PAC-1 was dosed from 75 to 750 mg daily orally (7 dose levels (DL)) on days 1-21 on 28 days cycle. For all dose cohorts, PAC-1 PK was assessed following doses administered on days 1 and 21 of the first cycle. In component 2, PAC-1 is dosed from 375 to 750 mg daily (up to 4 DL) plus temozolomide orally 150 mg/m2 daily for 5 days. PAC-1 PK was assessed following doses administered on days 7 and 12 and temozolomide PK is performed on Day 12 of the first cycle. Disease assessment was done every 2 cycles. Neurologic and neurocognitive function (NNCF) tests were performed throughout the study due to concern for neurotoxicity. Results: Forty-four patients were enrolled in part 1 and 12 in component 2. In part 1, at DL 1-5 no dose-limiting toxicities (DLTs) were observed. DL 6 was expanded to 6 patients due to one episode of intracranial bleed that occurred during cycle 4 of treatment, assessed initially as possibly related to study drug, but later attributed to new brain metastasis and unrelated to PAC-1. Grade 1 and 2 neurological adverse events such as ataxia and hallucinations were noted in DL 7 and this DL was expanded to 9 patients to assure safety. All other serious adverse events were determined to be unrelated or unlikely related to the study drug. Eleven patients (25%) did not complete 2 cycles of treatment due to rapid progression or withdrawal. Eight patients (18%) had stable disease for at least 2 cycles. One patient (2%) had partial response. In component 2 treating refractory high-grade astrocytomas, 7 patients were accrued to DL 1, and 5 patients to DL 2. No DLT was observed. Nine patients were evaluable for response. Five patients (42 %) had disease progression. Two patients (16%) had stable disease for at least 2 cycles, and two (16%) had partial response. Review of NNCF testing showed a consistent pattern of stable neurologic and cognitive evaluations. The PK data demonstrated satisfactory systemic delivery of PAC-1 following oral administration and acceptable absorption and elimination profiles. Conclusions: Single agent PAC-1 is well tolerated and 750 mg was determined to be the MTD. The combination of PAC-1 plus temozolomide continues to enroll patients in this study. Citation Format: Oana C. Danciu, M. Kelly Nicholas, Matthias Holdhoff, Richard A. Peterson, Neeta Venepalli, Rozina Chowdhery, Paul J. Hergenrother, Theodore M. Tarasow, Arkadiusz Z. Dudek. Phase I study of procaspase activating compound -1 (PAC-1) in the treatment of advanced malignancies and in combination with temozolomide in refractory high-grade astrocytomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT027.

TPS194 Background: The standard of care for locally advanced esophageal adenocarcinoma is concurrent chemoradiation (CRT) followed by esophagectomy with lymphadenectomy. Approximately 30% of patients achieve a complete pathologic response (pCR) with this multimodality approach, which has been correlated with improved disease-free survival. The risk of relapse in the remaining 70% of patients who have pathologic evidence of persistent disease in the surgical specimen is extremely high and estimated at 60-70%. Preclinical studies have demonstrated that radiation with or without concurrent chemotherapy upregulates the programmed cell death receptor- 1 (PD-1) pathway by inducing a local inflammatory response, an effect that persists for a number of months after cessation of therapy. Durvalumab is a selective, high affinity, engineered human IgG1 monoclonal antibody that blocks PD-L1 binding to PD-1 and CD80, and has shown activity in metastatic esophageal cancer. The aim of this study is to evaluate efficacy of post-operative durvalumab with respect to decreasing the relapse rate in patients who do not achieve pCR following CRT. Methods: Patients with esophageal adenocarcinoma who have pathologic evidence of persistent disease in the surgical specimen following neoadjuvant concurrent CRT (carboplatin plus paclitaxel or cisplatin plus 5-FU) and R0 resection are eligible for enrollment on this single arm phase II study. Durvalumab 1500mg IV every 4 weeks is started within 1-3 months of surgery and continued for up to 1 year. The primary endpoint is 1-year relapse free survival (RFS). Secondary endpoint is to assess the incidence and severity of overall and treatment related adverse events. Exploratory endpoints include PDL1 expression in tumor and tumor infiltrating lymphocytes, assessment of Immunoscore within the center and invasive margin of the tumor, and the correlation between changes in circulating tumor cell numbers in response to PD-L1 inhibition. The study is currently open to accrual at 5 sites in the Big Ten Cancer Research Consortium and 17 of the planned 23 patients have been enrolled within the past 14 months. Clinical trial information: NCT02639065.

2587Background: Pazopanib is a multi - kinase inhibitor that inhibits angiogenesis. Alisertib is a highly selective inhibitor of mitotic Aurora A Kinase that has been shown to disrupt chromosome se...

TPS493 Background: Mucin 1 (MUC1) is a tumor associated membrane-bound glycoprotein that promotes oncogenesis through promotion of epithelial cell polarity loss, anti-apoptosis, and hypoxia driven angiogenesis. MUC1 overexpression is associated with aggressive behavior and poor outcomes in pancreatic ductal adenocarcinoma (PDAC), and increased resistance to gemcitabine (G) in vitro. BTH1704 (BTH) is a humanized monoclonal antibody (MAb) targeting aberrantly glycosylated MUC1. Imprime PGG (PGG) is a soluble yeast-derived b 1,3/1,6 glucan that binds complement receptor 3 (CR3) on innate immune cells priming them to exert anti-tumor activity against complement (iC3b) opsonized tumor cells. Following incubation of PGG with whole blood from healthy subjects, variability in PGG binding to neutrophils and monocytes has been observed, with higher binding and functional changes correlating with higher levels of endogenous anti-b glucan antibodies. BTH binds to antigens (MUC1), leading to iC3b opsonization of tumor cells thus, allowing PGG-primed leukocytes to kill the iC3b-opsonized tumor cells. This forms the rationale for testing BTH1704 combined with G + PGG. Methods: This is a single institution Phase 1b dose escalation study with a standard 3x3 design to determine the maximal administered dose (MAD) of BTH combined with G + PGG in patients with previously treated advanced PDAC.Each dose cohort includes at least one subject with high and one low PGG binding capability. Primary objectives: establish MAD of BTH combined with G + PGG. Secondary objectives: characterize adverse effects, clinical response, time to progression, progression free and overall survival. Correlative objectives: quantify PGG binding, MDSC phenotyping of PBMC, anti b glucan antibody levels, MUC1 IHC. Inclusion criteria: confirmed advanced PDAC, ECOG PS 0-2, rest period 2-6 weeks from prior first- or second-line treatment. Exclusion criteria: uncontrolled chronic illness. Administration and design: BTH and PGG are administered on days 1, 8, 15, and 22 of a 28-day cycle; G is administered on days 1, 8, and 15. The study is currently enrolling patients. Clinical trial information: NCT02132403. Clinical trial information: NCT02132403.

87 Background: The University of Illinois Cancer Center (UICC) utilizes nurse (RN) visits for laboratory review and toxicity evaluations for patients (pts) receiving chemotherapy. Upon review of nursing visits, we observed that RN visit documentation for neutropenia was variable without standard language, communication with physicians (MD), or requirement for MD evaluation. We sought to implement an early intervention strategy to prevent morbidity and mortality from high risk neutropenia (HRN). Methods: A multidisciplinary task force of oncology RNs and MDs created actual and ideal process maps, from identification of neutropenia to patient disposition. We developed a Standard Operating Protocol (SOP) involving a HRN checklist (created based on NCCN and ISDA guidelines) and new process for triage of HRN pts. RNs were required to complete the HRN checklist within the electronic health record for all pts with ANC < 1,000. If high risk features were identified, MD evaluation was required within 1 hour of RN call, with SOAP note and attending notification. Results: Over an 8 week period, 17 HRN templates were generated. The process and checklist were adjusted after the first 4 weeks with clinic wide feedback. Within the first 4 weeks, 8 templates were generated (5 MD, 3 RN); no patients met high risk neutropenia criteria and all were discharged home. Within the second 4 weeks, 9 templates were generated (3 MD, 6 RN); 3 HRN pts were identified with two direct admissions and one home discharge with favorable outcomes. Clinic staff reported greater understanding of HRN, increased satisfaction with multidisciplinary interactions, and more comfort with calling MDs for prompt patient evaluation. Conclusions: UICC successfully piloted the creation and implementation of an early identification and intervention strategy for HRN with strong multidisciplinary support. Compared to the prior 6 month period, we found that use of the SOP and checklist resulted in improvement in evaluation of quality and timeliness of HRN pts and prevented morbidity and mortality. Additionally, the checklist provoked critical thinking from end users with more thorough patient evaluations and improved documentation, resulting in aggressive intervention and better outcomes.

TPS2635 Background: The insulin-like growth factor 1 receptor (IGF-1R) is overexpressed in multiple malignancies, including breast, prostate, lung, colorectal, CLL, T-ALL, and mantle cell lymphoma....