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Objective Certain eligibility criteria for Phase 1 cancer clinical trials may impede successful patient enrollment onto a study. We evaluated patient-specific or study-specific reasons for screen failures on Phase 1 oncology clinical trials and discuss factors which may inhibit subject enrollment. Methods Thirty-eight Phase 1 clinical trials for solid tumors meeting eligibility criteria and opened for enrollment between February 2006 and February 2011 at one oncology Phase 1 program were examined. Categorical reasons for screen failures and patients’ demographics were examined and compared to characteristics of patients that successfully enrolled on a Phase 1 trial. Results There were a total of 583 successful Phase 1 enrollment and dose administration events out of 773 Phase 1 consent events (75.4 % dose success rate). The three most common reasons for screen failure were: out of protocol-specified range for chemistry, development of an interval medical issue that precluded proceeding with study participation, and subject declining participation after signing consent. Living further away from the Phase 1 program and receipt of fewer prior lines of systemic chemotherapy were significantly associated with increased screen failures. Conclusion Screen failures for Phase 1 studies are not uncommon (24.6 %). When a protocol required tumor or host analyte is not required, most screen failures are due to out of protocol-specified range for chemistry or the development of an interval medical issue. Screen failure rates were increased when patients had longer travel distances and fewer prior lines of systemic chemotherapy.

The use of 18-fluorodeoxyglucose (FDG) positron emission tomography with computed tomography (PET/CT) in subjects with advanced basal cell carcinoma (BCC) has not been fully explored due to the rarity of disease presentation. This study evaluated PET/CTs from subjects with advanced BCC participating in a phase I dose-escalation clinical trial of vismodegib. Fourteen subjects with BCC were imaged with 18-FDG PET/CT for lesion identification and response categorizing (European Organisation for Research and Treatment for Cancer [EORTC] and PET response criteria in solid tumors [PERCIST] 1.0). Several parameters including metabolic activity of target lesions, site of disease presentation and spread, treatment response, and prognostic significance of metabolic activity following therapy were evaluated. All subjects exhibited at least one hypermetabolic lesion. Most subjects had only four organ systems involved at study enrollment: skin–muscle (93%), lung (57%), lymph nodes (29%), and bone (21%). SUVmax measured across all lesions decreased (median 33%, SD ± 45%) following therapy with metabolic activity normalizing or disappearing in 42% of lesions. No significant difference was observed between EORTC and PERCIST 1.0. Subjects that demonstrated at least a 33% reduction in SUVmax from baseline had a significantly longer progression-free survival (PFS) (median 17 months, 95% confidence interval [CI] ±4 months vs. 9 months, 95% CI ±5 months, P = 0.038) and overall survival (OS) (median 24 months, 95% CI ±4 months vs. 17 months, 95% CI ±13 months, P = 0.019). BCC lesions are hypermetabolic on 18-FDG PET/CT. A decrease in SUVmax was associated with improved PFS and OS. These results further support the incorporation of 18-FDG PET/CT scans in advanced BCC management.

Marantic endocarditis, otherwise known as nonbacterial thrombotic endocarditis (NBTE), is a well-documented phenomenon due to hypercoagulability from an underlying cause. It has been associated with a variety of inflammatory states including malignancy. Surprisingly, although hypercoagulability is often seen in patients with pancreatic cancer, marantic endocarditis has rarely been reported antemortem in this population. We report three cases of marantic endocarditis in patients with advanced pancreatic cancer. In two instances, the patients’ neurological symptoms preceded the diagnosis of advanced pancreatic cancer. Health care professionals should be alert to the possibility of marantic endocarditis in any patient with cancer, especially pancreatic cancer, who presents with symptoms of neurological dysfunction or an arterial thrombotic event. Prompt diagnosis and treatment with heparin, unfractionated or low molecular weight, may prevent catastrophic CNS events and decrease morbidity in patients with pancreatic cancer and other malignancies.

Tumor responses in advanced basal cell carcinoma (BCC) have been observed in clinical trials with vismodegib, a SMO antagonist. The result of SMO antagonism is inhibition Hedgehog Signaling Pathway (HHSP) downstream target genes. HHSP inhibition has been shown to affect stem cells responsible for blood, mammary, and neural development. We report on our experience of treating two patients with advanced BCC participating. These two patients have had no new BCCs develop for at least 2.25 years. Both patients have been receiving ongoing daily treatment with vismodegib for greater than 2.75 years without experiencing any significant side effects. After prolonged continuous daily dosing with a SMO antagonist, we have not observed a significant alteration in hematologic parameters or physical abnormalities of the pectoral regions of two patients with advanced BCC.

Introduction Analysis of biological samples for volatile organic compound (VOC) profiles or fingerprints can potentially be utilized as a non-invasive, early stage diagnostic tool for disease related to metabolic processes. A hypothesis was presented in 1989 that dogs could detect malignant tumors by scent and several studies of canine scent detection for cancer followed. Our team has taken an analogous approach using solid phase microextraction in combination with capillary gas chromatography time of flight mass spectrometry (SPME GC-TOFMS) in place of canine scent detection to discover indicators for pancreatic cancer, a deadly cancer difficult to detect in its early development stage. VOCs are not commonly considered in “biomarker” analysis of clinical samples which usually require extensive pre-processing. The VOC fingerprint from a biological sample presumes many such substances are products, by-products, and waste resulting from human metabolism (and/or symbiotic microbiom) of nutrients and intermediates from endogenous processes, absorbed environmental contaminants, and endo/exogenous bacterial metabolism. Methods IRB approval was obtained to enroll patients with advanced pancreatic cancer and healthy volunteers. Blood was collected in pre-conditioned vacutainers from 11 patients and 5 healthy volunteers, all non-smokers, no chemotherapy in preceding 5 days, and analyzed within 2 weeks. SPME GC-TOFMS is a means for eliminating the biological matrix and pre-concentrating specific ranges of complex volatile fraction polarities at low concentrations and a very sensitive analytical instrumental platform for the characterization of VOC chromatographic profiles extracted from the 3ml blood samples. Multivariate statistical methods were used to analysis retention time exact mass observations and integrated peak areas. Results Even with the numerous variables contributing to an already diverse underlying metabolism of each participant, our chemometric approach did discriminate between “healthy” volunteers and the cancer patients with a 5% prediction error using a “leave one out” statistical analysis for 37 samplesb from the 16 subjects. Key retention time and exact mass observations from a fiber specific SPME were associated to preliminary molecule identifications via NIST data base searches. Our procedures for system tune, calibration, and monitoring achieved a response stability over a 1 month period of ∼10% rsd and accurate mass measurement of at least 5 mDa (30 - 300 Da) using benzene-d6, BFB, and naphthalene-d8. Conclusions VOC fingerprints from a SPME GC-TOFMS analysis of blood can be successful in discovering differentiating indicators related to APC. Future work will involve other SPME fibers and more samples. (Supported by the IBIS & Scottsdale Health Care Foundations) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1264. doi:1538-7445.AM2012-1264