Current State of Clinical Trials at Shizuoka Cancer Center, and Steps Taken to Improve Pharmaceutical Department Performance

BackgroundImage guided intra-tumor administration of investigational immunotherapeutic agents represents an expanding field of interest. We present a retrospective review of the safety, feasibility & technical nuances of real-time image guidance for injection & biopsy across a spectrum of extracranial solid malignancies utilizing the discipline of Interventional Radiology.MethodsPatients who were enrolled in image guided intratumoral immunotherapy injection (ITITI) clinical trials over a 6 year period (2013–19) at a single tertiary care cancer center were included in this analysis. Malignancy, location, imaging guidance utilized for ITITI & biopsy for injected (adscopal) & non-injected (abscopal) lesions were determined and categorized. Peri-procedural adverse events were noted.Results262 pts (146 female, 61 yrs median) participating in 29 immunotherapeutic clinical trials (TLR & STING agonists, gene therapy, anti CD-40, viral/bacterial/metabolic oncolytics) met study criteria. Malignancies included melanoma 88, sarcoma 32, colorectal 29, breast 23, lung 17, head & neck 15, ovarian 8, neuroendocrine 7, pancreatic adenocarcinoma 6, 3 each (cholangioCA, endometrial, bladder, GI tract), 2 each (RCC, thymicCA, lymphoma, merkel cell, prostate) & others 1 each (CUP, GIST, dermatofibrosarcoma, DSRT, neuroblastoma, thyroid). All 169 & 93 patients received the intended 1371 ITITI in parietal (abdominal/chest wall, extremity, neck, pelvis) or visceral (liver, lung, peritoneum, adrenal) locations respectively; 83 patients received lymph node injections within either location. Imaging guidance was US in 68% of the cohort (US 161, CT+US 19); CT was used in 30% (81) & MRI in 1 patient. Median diameter of the ITITI lesion was 32 mm (8–230 mm). Median volume of the ITITI therapeutic material/session was 2 ml (1–6.9 ml). Lesions were accessed using a coaxial technique. ITITI delivery needles used at operator preference & tailored to lesion characteristics were either a 21G/22G Chiba, 21G Profusion (Cook Medical), 22G Morrison (AprioMed), 25G hypodermic (BD) & 18G Quadrafuse (Rex Medical). 2840 core biopsies (>18G Tru-cut core, Mission, Bard Medical) were performed in 237 patients during 690 procedures; biopsy sessions were often concurrent & of the ITITI site. 137 patients also underwent biopsy of a non-ITITI site (89 parietal location). Dimensions of the non-ITITI lesion were median 10 mm (7–113 mm); US image guidance was used in 97 patients (72%) to obtain a total of 1257, >18G Tru-core samples. 1.3% of injections resulted in SAE (NCI CTC AE >3) and 0.5% of 4097 biopsies developed major complications (SIR Criteria); both categories were manageable.ConclusionsUtilizing real time image guidance, ITITI to the administration of a myriad of investigational immunotherapeutic agents with concomitant biopsy procedures to date are associated with a high technical success rate & favorable safety profile.AcknowledgementsJoshua Hein, Mara Castaneda, Jyotsna Pera, Yunfang Jiang,Shuang Liu, Holly Liu and Anna LuiTrial RegistrationN/AEthics ApprovalThe study was approved by Institution’s Ethics Board, approval number 2020-0536: A retrospective study to determine the safety, feasibility and technical challenges of real-time image guidance for intra-tumor injection and biopsy across multiple solid tumors.Consent2020-0536 Waiver of Informed ConsentReferenceSheth RA, Murthy R, Hong DS, et al. Assessment of image-guided intratumoral delivery of immunotherapeutics in patients with cancer. JAMA Netw Open 2020;3(7):e207911. doi:10.1001/jamanetworkopen.2020.7911

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Conceptual Framework to Support Clinical Trial Optimization and End-to-End Enrollment Workflow

JCO Clinical Cancer Informatics ◽

10.1200/cci.19.00033 ◽

2019 ◽

pp. 1-10 ◽

Cited By ~ 3

Author(s):

Neha M. Jain ◽

Alison Culley ◽

Teresa Knoop ◽

Christine Micheel ◽

Travis Osterman ◽

...

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Knowledge Representation ◽

Conceptual Framework ◽

Trial Design ◽

Clinical Trial Design ◽

Prospective Clinical Trial ◽

Future Trends ◽

Current State ◽

Evaluation Strategies

In this work, we present a conceptual framework to support clinical trial optimization and enrollment workflows and review the current state, limitations, and future trends in this space. This framework includes knowledge representation of clinical trials, clinical trial optimization, clinical trial design, enrollment workflows for prospective clinical trial matching, waitlist management, and, finally, evaluation strategies for assessing improvement.

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The United States’ Regulatory Environment Is Evolving to Accommodate a Coming Boom in Gene Therapy Research

Applied Biosafety ◽

10.1177/1535676019854866 ◽

2019 ◽

Vol 24 (3) ◽

pp. 147-152 ◽

Cited By ~ 2

Author(s):

Daniel Eisenman

Keyword(s):

United States ◽

Gene Therapy ◽

Clinical Trials ◽

The United States ◽

Regulatory Environment ◽

Evidence Based ◽

Regulatory Structure ◽

Regulatory Changes ◽

Current State ◽

Therapy Field

Introduction: A dramatic increase in the number of clinical trials involving gene-modified cell therapy and gene therapy is taking place. The field is on the verge of a boom, and the regulatory environment is evolving to accommodate the growth. Discussion: This commentary summarizes the current state of the field, including an overview of the growth. The United States (US) regulatory structure for gene therapy will be summarized, and the evolution of the oversight structure will be explained. Conclusion: The gene therapy field has recently produced its first FDA-approved therapeutics and has a pipeline of other investigational products in the final stages of clinical trials before they can be evaluated by the FDA as safe and effective therapeutics. As research continues to evolve, so must the oversight structure. Biosafety professionals and IBCs have always played key roles in contributing to the safe, evidence-based advancement of gene therapy research. With the recent regulatory changes and current surge in gene therapy research, the importance of those roles has increased dramatically.

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Barriers to Enrollment of Elderly Adults in Early-Phase Cancer Clinical Trials

Journal of Oncology Practice ◽

10.1200/jop.0842001 ◽

2008 ◽

Vol 4 (4) ◽

pp. 162-168 ◽

Cited By ~ 45

Author(s):

Michele Basche ◽

Anna E. Barón ◽

S. Gail Eckhardt ◽

Lodovico Balducci ◽

Martha Persky ◽

...

Keyword(s):

Clinical Trials ◽

Early Phase ◽

Age Groups ◽

Experimental Treatment ◽

Cancer Center ◽

Cancer Clinical Trials ◽

Sources Of Information ◽

Barriers To Participation ◽

University Center ◽

Barriers To Enrollment

Purpose: To describe patient/family and logistical barriers to participation in university-based, early-phase cancer clinical trials for adults age ≥ 65 years, and to identify influences on their decisions to participate. Participants and Methods: In-person surveys were administered to subjects age ≥ 65 years with advanced tumors who had received prior chemotherapy. Subjects were recruited from private medical oncology practices collaborating with the University of Colorado and Moffitt Cancer Center research networks. Results: Three hundred individuals (51% age 65 to 74 and 49% age 75 or older) responded. Overall, 60% reported one or more barriers to participation in an early-phase trial; logistical barriers such as driving or time demands (34%) or reluctance to be treated at a university center (21%) were most common. Seniors age 75 or older were more reluctant to be treated at a university center (27% v 14%; P = .005), or concerned about loss of continuity with their primary oncologist (24% v 15%, P = .05). Older seniors were also significantly more reluctant than younger seniors to consider treatments with substantial nausea, vomiting, or fatigue. Older and younger seniors differed little in their preferred sources of information; both age groups emphasized the importance of the primary oncologist (100%), a nurse who provides experimental treatment (93%), other patients (83%) or acquaintances who had received experimental treatment (83%). Conclusion: Potential strategies to overcome barriers to enrollment of seniors into early-phase trials include providing more information about trials to community oncologists and prospective enrollees and assisting these individuals in navigating logistical barriers to enrollment.

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Improving hematology/oncology clinical research recruitment via universal prescreening: The VA Connecticut (VACT) Cancer Center experience.

Journal of Clinical Oncology ◽

10.1200/jco.2020.39.28_suppl.79 ◽

2021 ◽

Vol 39 (28_suppl) ◽

pp. 79-79

Author(s):

Jenny Jing Xiang ◽

Alicia Roy ◽

Christine Summers ◽

Monica Delvy ◽

Jessica Lee O'Donovan ◽

...

Keyword(s):

Lung Cancer ◽

Clinical Trials ◽

Clinical Research ◽

Cancer Patients ◽

Cancer Center ◽

Cancer Type ◽

Eligibility Criteria ◽

Research Recruitment ◽

Lung Cancer Patients ◽

Study Enrollment

79 Background: Patient-trial matching is a critical step in clinical research recruitment that requires extensive review of clinical data and trial requirements. Prescreening, defined as identifying potentially eligible patients using select eligibility criteria, may streamline the process and increase study enrollment. We describe the real-world experience of implementing a standardized, universal clinical research prescreening protocol within a VA cancer center and its impact on research enrollment. Methods: An IRB approved prescreening protocol was implemented at the VACT Cancer Center in March 2017. All patients with a suspected or confirmed diagnosis of cancer are identified through tumor boards, oncology consults, and clinic lists. Research coordinators perform chart review and manually enter patient demographics, cancer type and stage, and treatment history into a REDCap (Research Electronic Data Capture) database. All clinical trials and their eligibility criteria are also entered into REDCap and updated regularly. REDCap generates real time lists of potential research studies for each patient based on his/her recorded data. The primary oncologist is alerted to a patient’s potential eligibility prior to upcoming clinic visits and thus can plan to discuss clinical research enrollment as appropriate. Results: From March 2017 to December 2020, a total of 2548 unique patients were prescreened into REDCAP. The mean age was 71.5 years, 97.5% were male, and 15.5% were African American. 32.57 % patients had genitourinary cancer, 17.15% had lung cancer, and 46.15% were undergoing malignancy workup. 1412 patients were potentially eligible after prescreening and 556 patients were ultimately enrolled in studies. The number of patients enrolled on therapeutic clinical trials increased after the implementation of the prescreening protocol (35 in 2017, 64 in 2018, 78 in 2019, and 55 in 2020 despite the COVID19 pandemic). Biorepository study enrollment increased from 8 in 2019 to 15 in 2020. The prescreening protocol also enabled 200 patients to be enrolled onto a lung nodule liquid biopsy study from 2017 to 2019. Our prescreening process captured 98.57% of lung cancer patients entered into the cancer registry during the same time period. Conclusions: Universal prescreening streamlined research recruitment operations and was associated with yearly increases in clinical research enrollment at a VA cancer center. Our protocol identified most new lung cancer patients, suggesting that, at least for this malignancy, potential study patients were not missed. The protocol was integral in our program becoming the top accruing VA site for NCI’s National Clinical Trial Network (NCTN) studies since 2019.

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Strategies for the Administration of a Clinical Trials Infrastructure: Lessons from a Comprehensive Cancer Center

Cancer Clinical Trials: Proactive Strategies - Cancer Treatment and Research ◽

10.1007/978-0-387-33225-3_14 ◽

2007 ◽

pp. 241-274 ◽

Cited By ~ 1

Author(s):

Leonard A. Zwelling ◽

Carleen A. Brunelli

Keyword(s):

Clinical Trials ◽

Comprehensive Cancer Center ◽

Cancer Center

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Status Quo and Trends of Intra-Arterial Therapy for Brain Tumors: A Bibliometric and Clinical Trials Analysis

Pharmaceutics ◽

10.3390/pharmaceutics13111885 ◽

2021 ◽

Vol 13 (11) ◽

pp. 1885

Author(s):

Julian S. Rechberger ◽

Frederic Thiele ◽

David J. Daniels

Keyword(s):

Drug Delivery ◽

Clinical Trials ◽

Brain Tumors ◽

Phase 1 ◽

Citation Count ◽

Tumor Therapy ◽

The United States ◽

Blood Brain Barrier Disruption ◽

Current State ◽

Brain Barrier Disruption

Intra-arterial drug delivery circumvents the first-pass effect and is believed to increase both efficacy and tolerability of primary and metastatic brain tumor therapy. The aim of this update is to report on pertinent articles and clinical trials to better understand the research landscape to date and future directions. Elsevier’s Scopus and ClinicalTrials.gov databases were reviewed in August 2021 for all possible articles and clinical trials of intra-arterial drug injection as a treatment strategy for brain tumors. Entries were screened against predefined selection criteria and various parameters were summarized. Twenty clinical trials and 271 articles satisfied all inclusion criteria. In terms of articles, 201 (74%) were primarily clinical and 70 (26%) were basic science, published in a total of 120 different journals. Median values were: publication year, 1986 (range, 1962–2021); citation count, 15 (range, 0–607); number of authors, 5 (range, 1–18). Pertaining to clinical trials, 9 (45%) were phase 1 trials, with median expected start and completion years in 2011 (range, 1998–2019) and 2022 (range, 2008–2025), respectively. Only one (5%) trial has reported results to date. Glioma was the most common tumor indication reported in both articles (68%) and trials (75%). There were 215 (79%) articles investigating chemotherapy, while 13 (65%) trials evaluated targeted therapy. Transient blood–brain barrier disruption was the commonest strategy for articles (27%) and trials (60%) to optimize intra-arterial therapy. Articles and trials predominately originated in the United States (50% and 90%, respectively). In this bibliometric and clinical trials analysis, we discuss the current state and trends of intra-arterial therapy for brain tumors. Most articles were clinical, and traditional anti-cancer agents and drug delivery strategies were commonly studied. This was reflected in clinical trials, of which only a single study had reported outcomes. We anticipate future efforts to involve novel therapeutic and procedural strategies based on recent advances in the field.

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Key Barriers to Clinical Trial Enrolment: A Survey of Clinical Trial Staff at an NCI Designated Cancer Center

Blood ◽

10.1182/blood-2019-126257 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5864-5864

Author(s):

Amany R. Keruakous ◽

Adam S. Asch

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Cultural Bias ◽

Cancer Center ◽

Exclusion Criteria ◽

Strict Inclusion ◽

Trial Protocols ◽

Trial Staff ◽

Disease Site ◽

Patient Enrolment

Background: Clinical trials, key elements of the processes that account for many of the recent advances in cancer care, are becoming more complex and challenging to conduct. The Stephenson Cancer Center (SCC) has been the lead accruer to NCI-LAP trials over the past three years, and in addition, fields investigator initiated and industry sponsored trials. To identify opportunities for continued improvement in clinical trial enrolment, we sought to identify the obstacles encountered by our clinical trial staff in these activities. Method: We conducted a survey of our research staff including all research nurses and disease site coordinators who participate in recruitment, screening, consenting, data collection and compliance. The survey, sent by email to the clinical trial list-serve at SCC (90 staff member), invited respondents to enumerate obstacles to patient participation in clinical trials. We then performed a follow up meeting with our research coordinators to clarify responses. A total of 26 responses from 90 respondents were received and tabulated by disease site. Results: The most commonly reported obstacles to enrolment were, in descending order: communication/language barriers, cultural bias, time/procedure commitment, and complexity of the trial protocol, financial logistics, comorbidities, and stringent trial criteria. Respondents identified 83 obstacles as frequently encountered obstacles to enrolment. The 83 reported obstacles were classified into 9 categories and organized by disease site as presented in tabular format (below). The most commonly identified obstacles to patient enrolment were communication and language barriers. In patients for whom Spanish is the primary language this was a universal obstacle, as there is a lack of consistent Spanish consents across the clinical trial portfolio. Cultural bias, as an obstacle was manifested as a general mistrust by prospective trial participants of experimental therapies and clinical trials. After communication and cultural bias as barriers, travel requirements and the associated expenses playing a role in patients from rural areas were identified as the most commonly encountered barrier. The complexity of trial protocols and the associated large number of clinic visits, frequent laboratory and imaging tests were also identified as common obstacles. Clinical trial complexity with strict inclusion and exclusion criteria and trial-specified biopsies were frequently cited. Implications: In this descriptive study, common barriers to patient enrolment in clinical trials were identified by clinical trial staff. Assessing barriers encountered by clinical trial staff is infrequently used as a metric for improving clinical trial enrolment, but provides important perspective. In our study, some obstacles are inherent in our patient populations, others appear to be actionable. Development of Spanish language consents and specific programs to overcome negative bias regarding clinical trials are potential areas for improvement. The complexity of clinical trial protocols and the increasingly strict inclusion/exclusion criteria, are issues that will require consideration and action at the level of the cooperative groups and industry. Disclosures No relevant conflicts of interest to declare.

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