James Wallace

Randomized Phase Ib/II Study of Gemcitabine Plus Placebo or Vismodegib, a Hedgehog Pathway Inhibitor, in Patients With Metastatic Pancreatic Cancer

Purpose Sonic hedgehog (SHH), an activating ligand of smoothened (SMO), is overexpressed in > 70% of pancreatic cancers (PCs). We investigated the impact of vismodegib, an SHH antagonist, plus gemcitabine (GV) or gemcitabine plus placebo (GP) in a multicenter phase Ib/randomized phase II trial and preclinical PC models. Patients and Methods Patients with PC not amenable to curative therapy who had received no prior therapy for metastatic disease and had Karnofsky performance score ≥ 80 were enrolled. Patients were randomly assigned in a one-to-one ratio to GV or GP. The primary end point was progression-free-survival (PFS). Exploratory correlative studies included serial SHH serum levels and contrast perfusion computed tomography imaging. To further investigate putative biologic mechanisms of SMO inhibition, two autochthonous pancreatic cancer models (KrasG12D; p16/p19fl/fl; Pdx1-Cre and KrasG12D; p53R270H/wt; Pdx1-Cre) were studied. Results No safety issues were identified in the phase Ib portion (n = 7), and the phase II study enrolled 106 evaluable patients (n = 53 in each arm). Median PFS was 4.0 and 2.5 months for GV and GP arms, respectively (95% CI, 2.5 to 5.3 and 1.9 to 3.8, respectively; adjusted hazard ratio, 0.81; 95% CI, 0.54 to 1.21; P = .30). Median overall survival (OS) was 6.9 and 6.1 months for GV and GP arms, respectively (95% CI, 5.8 to 8.0 and 5.0 to 8.0, respectively; adjusted hazard ratio, 1.04; 95% CI, 0.69 to 1.58; P = .84). Response rates were not significantly different. There were no significant associations between correlative markers and overall response rate, PFS, or OS. Preclinical trials revealed no significant differences with vismodegib in drug delivery, tumor growth rate, or OS in either model. Conclusion The addition of vismodegib to gemcitabine in an unselected cohort did not improve overall response rate, PFS, or OS in patients with metastatic PC. Our preclinical and clinical results revealed no statistically significant differences with respect to drug delivery or treatment efficacy using vismodegib.

Treatment Rationale and Study Design for a Randomized, Double-Blind, Placebo-Controlled Phase II Study Evaluating Onartuzumab (MetMAb) in Combination With Bevacizumab Plus mFOLFOX-6 in Patients With Previously Untreated Metastatic Colorectal Cancer

BACKGROUND Dysregulation of the hepatocyte growth factor (HGF)/MET pathway is associated with poor prognosis, more aggressive biological characteristics of the tumor, and shortened survival in patients with metastatic colorectal cancer (mCRC). Onartuzumab (MetMAb) is a recombinant humanized monovalent monoclonal antibody directed against MET. We present the treatment rationale and protocol for an ongoing randomized multicenter placebo-controlled phase II study designed to evaluate the efficacy and safety of MetMAb combined with bevacizumab and mFOLFOX-6 (5-fluoruracil, leucovorin, and oxaliplatin). PATIENTS AND METHODS Eligible patients with previously untreated mCRC are randomized 1:1 to either mFOLFOX-6 combined with bevacizumab and placebo followed by 5-fluorouracil/leucovorin plus bevacizumab and placebo or mFOLFOX6, bevacizumab plus MetMAb followed by 5 FU/LV, bevacizumab, and MetMAb. The primary end point of this study is progression-free survival (PFS) in the intent-to-treat (ITT) population. Secondary end points include overall survival (OS), objective response rate, and safety. Subanalyses will be performed to evaluate the effect of MET receptor expression on study primary and secondary end points. Correlative studies will be performed on tissue- and blood-derived biomarkers related to both HGF/MET signaling and other associated pathway markers.

Shared Goal Setting in Team-Based Geriatric Oncology

We present the case of a 92-year-old man, MH, who was given a diagnosis of colorectal cancer. His primary care physician, surgeon, geriatric oncologist, and family members all played important roles in his care. MHs case is an example of a lack of explicit shared goal setting by the health care providers with the patient and family members and how that impeded care planning and health. This case demonstrates the importance of explicitly discussing and establishing shared goals in team-based cancer care delivery early on and throughout the care process, especially for older adults. Each individual members goals should be understood as they fit within the overarching shared team goals. We emphasize that shared goal setting and alignment of individual goals is a dynamic process that must occur several times at critical decision points throughout a patients care continuum. Providers and researchers can use this illustrative case to consider their own work and contemplate how shared goal setting can improve patient-centered care and health outcomes in various team-based care settings. Shared goal setting among team members has been demonstrated to improve outcomes in other contexts. However, we stress, that little investigation into the impact of shared goal setting on team-based cancer care delivery has been conducted. We list immediate research goals within team-based cancer care delivery that can provide a foundation for the understanding of the process and outcomes of shared goal setting.

The Chicago Thoracic Oncology Database Consortium: A Multisite Database Initiative.

Objective: An increasing amount of clinical data is available to biomedical researchers, but specifically designed database and informatics infrastructures are needed to handle this data effectively. Multiple research groups should be able to pool and share this data in an efficient manner. The Chicago Thoracic Oncology Database Consortium (CTODC) was created to standardize data collection and facilitate the pooling and sharing of data at institutions throughout Chicago and across the world. We assessed the CTODC by conducting a proof of principle investigation on lung cancer patients who took erlotinib. This study does not look into epidermal growth factor receptor (EGFR) mutations and tyrosine kinase inhibitors, but rather it discusses the development and utilization of the database involved. Methods: We have implemented the Thoracic Oncology Program Database Project (TOPDP) Microsoft Access, the Thoracic Oncology Research Program (TORP) Velos, and the TORP REDCap databases for translational research efforts. Standard operating procedures (SOPs) were created to document the construction and proper utilization of these databases. These SOPs have been made available freely to other institutions that have implemented their own databases patterned on these SOPs. Results: A cohort of 373 lung cancer patients who took erlotinib was identified. The EGFR mutation statuses of patients were analyzed. Out of the 70 patients that were tested, 55 had mutations while 15 did not. In terms of overall survival and duration of treatment, the cohort demonstrated that EGFR-mutated patients had a longer duration of erlotinib treatment and longer overall survival compared to their EGFR wild-type counterparts who received erlotinib. Discussion: The investigation successfully yielded data from all institutions of the CTODC. While the investigation identified challenges, such as the difficulty of data transfer and potential duplication of patient data, these issues can be resolved with greater cross-communication between institutions of the consortium. Conclusion: The investigation described herein demonstrates the successful data collection from multiple institutions in the context of a collaborative effort. The data presented here can be utilized as the basis for further collaborative efforts and/or development of larger and more streamlined databases within the consortium.

Cancer in Long-Term Care

This article describes the range of cancer patients in longterm care and provides a framework for clinical decision making. The benefits and burdens of providing standard therapy to a vulnerable population are discussed. To give more specific guidelines for advocates of treatment, skeptics, and others, the authors present best estimates of the current burden of cancer in the long-term care population and current screening guidelines that apply to the elderly under long-term care. Experience-based suggestions are offered for oncologists and clinicians involved in long-term care to help them respond to patient and family concerns about limitations of cancer care.

Cutaneous Eruption Related to Human Epidermal Growth Factor Receptor Inhibitors in Stage IV Colon Cancer

491 Lisa Guzman, RN, APN, CHPN, AOCN®, is an advanced practice nurse at Monroe Medical Oncology Clinic in Harvey and Tinley Park, IL, an instructor in the School of Nursing at Ivy Tech Community College in Gary, IN, and director of Blue Skies Hospice in Hammond, IN; Mark Kozloff, MD, is a doctor of oncology at Monroe Medical Oncology Clinic and an associate professor in the School of Medicine at the University of Chicago in Illinois; and James Wallace, MD, is a doctor of oncology and geriatrics and Alexander Starr, MD, is a doctor of oncology, both at Monroe Medical Oncology Clinic. Mention of specific products and opinions related to those products do not indicate or imply endorsement by the Clinical Journal of Oncology Nursing or the Oncology Nursing Society.