Submit to Special Issue Submit Abstract to Special Issue Review for Cancers Propose a Special Issue

Journal Menu

Journal Browser

► Journal Browser

Advances in Clinical Trials: Outcome, Innovations, Challenges, and Ethical Practice in Cancer Research 2025–2026

Special Issue Editors
Special Issue Information
Keywords
Benefits of Publishing in a Special Issue
Published Papers

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Clinical Research of Cancer".

Deadline for manuscript submissions: 30 June 2026 | Viewed by 34255

Share This Special Issue

Special Issue Editors

Prof. Dr. Naoto T. Ueno

E-Mail Website
Guest Editor

Translational and Clinical Research Program, University of Hawai’i Cancer Center, Honolulu, HI 96813, USA
Interests: triple-negative breast cancer; inflammatory breast cancer; bone metastasis; metastatic breast cancer; early drug development
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. David R. Gandara

E-Mail Website
Guest Editor

1. Co-Director, Center for Experimental Therapeutics in Cancer, University of California Davis Comprehensive Cancer Center, Sacramento, CA 95817, USA
2. Adjunct Clinical Professor, Translational and Clinical Research Program, University of Hawaii Cancer Center, Honolulu, HI 96813, USA
Interests: predictive biomarkers; cancer drug development; team science; population-related pharmaco-genomics; tumor mutational burden

Special Issue Information

Dear Colleagues,

Welcome to this Special Issue. We are at the forefront of an era that greatly values the dissemination of clinical trial outcomes of all phase studies (phase I, phase II, phase III, and phase IV), recognizing the profound impact of shared knowledge on the advancement of medical science. In this spirit, we encourage you to publish your findings, understanding that each piece of data, whether from trials that have met their endpoints or those that have not, propels us closer to scientific breakthroughs.

This Special Issue is committed to unraveling clinical trials' complexities and dynamic nature. Our objective is to thoroughly analyze their contemporary features, their design and implementation, and how they contribute to the forward momentum of medical research. We seek contributions in the form of original research, editorial insights, and comprehensive reviews that highlight innovative clinical trial outcomes.

We will spotlight pioneering methodologies that set new precedents in clinical research, including adaptive designs, patient-centered strategies, and the seamless incorporation of technology into trial management. Our readers will gain an intricate understanding of these methods in practice, the guiding regulatory frameworks, and the ethical pillars at their heart.

Moreover, we advocate for sharing all cancer clinical trial results openly. Regardless of their nature, each result significantly enriches our collective wisdom and influences the future path of scientific inquiry.

We invite you to share your experiences of success and the challenges faced during the execution of modern clinical trials. Your insights are invaluable in shaping the future of clinical research. Together, we strive to create a collaborative platform that fosters the development of treatments with a meaningful impact on our cancer community.

Mahalo for your unwavering commitment to advancing our understanding of this critical aspect of cancer clinical trials.

Prof. Dr. Naoto T. Ueno
Prof. Dr. David R. Gandara
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

phase I
phase II
phase III
phase IV
clinical trials
features
design
implementation
outcomes

Benefits of Publishing in a Special Issue

Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
Reprint: MDPI Books provides the opportunity to republish successful Special Issues in book format, both online and in print.

Further information on MDPI's Special Issue policies can be found here.

Published Papers (9 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Research

Jump to: Review, Other

12 pages, 561 KB

Open AccessArticle

Association Between Patient-Reported Outcomes and Overall Survival in Patients with Advanced NSCLC Treated with First-Line Cemiplimab-Based Therapy

by David R. Gandara, Tamta Makharadze, Mahmut Gümüş, Miranda Gogishvili, Ahmet Sezer, Eric Kim, Eric Yan, Frank Seebach, James Harnett and Ruben G. W. Quek

Cancers 2026, 18(6), 916; https://doi.org/10.3390/cancers18060916 - 12 Mar 2026

Viewed by 506

Abstract

Background/Objectives: Research on the association between change from baseline in patient-reported outcomes (PROs) and overall survival (OS) in patients with advanced non-small-cell lung cancer (NSCLC) exists. This study evaluated the association between post-baseline PROs and OS in patients with advanced NSCLC who received first-line cemiplimab-based therapy. Methods: We evaluated PRO data from two phase III studies (EMPOWER-Lung 1 [NCT03088540] and EMPOWER-Lung 3 [NCT03409614]) using a Cox proportional hazards model. Twelve pre-specified PRO scales from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and Quality of Life Questionnaire Lung Cancer 13 module were evaluated. Landmark analyses were conducted at 3, 6, 9, and 12 months. Time-dependent analyses using change from baseline PROs as a time-dependent covariate were conducted to evaluate the association of post-baseline PRO improvement with OS. Results: At the 3-month landmark, we observed a 56% reduction in the risk of death (HR = 0.44; 95% CI: 0.32–0.62; nominal p < 0.0001) among stable/improved vs. worsened/unobserved PROs for global health status (GHS)/quality of life (QoL). Results at the 6-, 9-, and 12-month landmarks of GHS/QoL were consistent with those at the 3-month landmark. Time-dependent analyses showed that every 10-point improvement in GHS/QoL was associated with a 31% reduction in the risk of death (HR = 0.69; 95% CI: 0.64–0.75; nominal p < 0.0001). Conclusions: In patients with advanced NSCLC who received first-line cemiplimab-based therapy, improvements in post-baseline PROs are associated with improved OS. These results may inform endpoint selection and interpretation of future clinical trials. Full article

(This article belongs to the Special Issue Advances in Clinical Trials: Outcome, Innovations, Challenges, and Ethical Practice in Cancer Research 2025–2026)

► Show Figures

Figure 1

17 pages, 1395 KB

Open AccessArticle

Phase II Study of Pegvorhyaluronidase Alfa (PEGPH20) and Pembrolizumab for Patients with Hyaluronan-High, Pretreated Metastatic Pancreatic Ductal Adenocarcinoma: PCRT16-001

by Elena Gabriela Chiorean, Sheela R. Damle, David B. Zhen, Martin Whittle, Ben George, Howard Hochster, Andrew L. Coveler, Andrew Hendifar, Tomislav Dragovich, Rachael A. Safyan, Gentry T. King, William P. Harris, Barbara Dion, Amy Stoll D’Astice, Arthur Lee, Shelley Thorsen, Sita Kugel, Adam Rosenthal and Sunil Hingorani

Cancers 2026, 18(3), 507; https://doi.org/10.3390/cancers18030507 - 3 Feb 2026

Viewed by 827

Abstract

Background: Stromal hyaluronic acid (HA) poses a physical barrier and protects tumor cells from immune surveillance. Stroma targeting with pegylated human recombinant PH20 hyaluronidase (PEGPH20) demonstrated improved infiltration of cytotoxic T-lymphocytes and delivery of chemotherapy and PD1/PD-L1 antibodies in tumor models. This multicenter phase II study of PEGPH20 plus pembrolizumab evaluated the efficacy, safety and immune and stromal biomarkers in patients with HA-high refractory metastatic pancreatic ductal adenocarcinoma (mPDA). Patients and Methods: Patients were treated with PEGPH20 3 µg/kg IV weekly and pembrolizumab 200 mg IV in 3-week cycles. Tumor and blood samples were collected at baseline and on-study for biomarker analyses. Results: Between May and November 2019, 38 patients were screened and 8 treated, with median age 68 years (range 60–73) and median two (range 1–4) prior therapies. The study was closed to accrual early by pharmaceutical sponsor. Treatment was well tolerated, with expected grade 1/2 musculoskeletal toxicities. Best response was stable disease in 2 of 7 evaluable patients (29%). Median overall and progression-free survival were 7.2 months (95% CI 1.2–11.8) and 1.5 months (95% CI 0.9–4.4), respectively. Prolonged survival (range 10.2–27.6 months) occurred in patients treated with subsequent chemotherapy. Higher baseline tumor T cell receptor (TCR) clonality correlated with longer survival. Conclusions: Pembrolizumab with PEGPH20 was safe but did not have significant efficacy in refractory HA-high metastatic PDA. Full article

(This article belongs to the Special Issue Advances in Clinical Trials: Outcome, Innovations, Challenges, and Ethical Practice in Cancer Research 2025–2026)

► Show Figures

Figure 1

17 pages, 1377 KB

Open AccessArticle

The Outcome and Impact of Academic Cancer Clinical Trials with Participation from Canadian Sites (2015–2024)

by Rebecca Y. Xu, Diana Kato, Victoria Percival, James Schoales, Stephen Sundquist, Raisa Chowdhury, Gregory R. Pond and Janet E. Dancey

Cancers 2025, 17(24), 4009; https://doi.org/10.3390/cancers17244009 - 16 Dec 2025

Viewed by 891

Abstract

Background/Objectives: Academically sponsored cancer clinical trials (ACCTs) are essential for advancing patient-centered care, particularly in areas underserved by commercial research. The Canadian Cancer Clinical Trials Network (3CTN) was established to support high-quality multi-center ACCTs through coordinated infrastructure and funding. Over ten years, funders provided an average of CAD 4.3 million annually (~CAD 0.11 per capita), primarily from federal and provincial sources. This study evaluates the outcomes and impact of trials supported by 3CTN between 2015 and 2024. Methods: We conducted a descriptive analysis of 350 ACCTs that stopped recruiting and had primary completion dates within the study period. Trial characteristics, results, publication rates, and incorporation into clinical guidelines were assessed using registry data, peer-reviewed publications, and structured searches of oncology guidelines. Results: Among these 350 closed trials, 116 were Phase III studies. Of these, 36% were incorporated into clinical practice guidelines, and 7% were likely to be incorporated. Overall, 81% of trials were published in journals, and 45% posted results in public registries. Trials addressed diverse cancer types, with notable contributions in rare cancers and vulnerable populations. Conclusions: 3CTN-supported ACCTs had high completion and reporting rates, with substantial influence on clinical practice. These findings highlight how sustained infrastructure and modest public investment can deliver meaningful improvements in cancer care and inform evidence-based policy. Full article

(This article belongs to the Special Issue Advances in Clinical Trials: Outcome, Innovations, Challenges, and Ethical Practice in Cancer Research 2025–2026)

► Show Figures

Figure 1

17 pages, 586 KB

Open AccessArticle

What Cachexia-Related Outcomes Are Measured in Lung Cancer Chemotherapy Clinical Trials?

by Valentina Razmovski-Naumovski, Anthony Tanous and Ross Valaire

Cancers 2025, 17(14), 2309; https://doi.org/10.3390/cancers17142309 - 11 Jul 2025

Cited by 1 | Viewed by 1915

Abstract

Background: Cachexia worsens prognosis, quality of life and chemotherapy treatment compliance of patients with lung cancer. Chemotherapy-induced cachexia has also been implicated in lowered mortality. This study aimed to evaluate the frequency of cachexia-related measures and symptoms as outcomes in lung cancer chemotherapy trial protocols and to examine how key trial characteristics influence them. Method: We conducted a cross-sectional data analysis of randomised controlled chemotherapy trials of lung cancer registered in four public trial registries between 2012 and 2023. Trial outcome measures included overall survival, treatment toxicity/side effects and cachexia-related indicators such as physical activity, weight/body mass index (BMI), dietary limitations, caloric intake and lean muscle mass. Symptom-related outcomes, including appetite loss, diarrhoea, pain, fatigue/insomnia, constipation, nausea, vomiting, dysphagia, dyspnoea and oral mucositis, were also extracted. Additionally, the number and type of performance status and assessment tool were recorded. Data were summarised descriptively. Chi-square tests were used to examine associations between trial outcomes and characteristics including cancer type, trial location, lead investigator/funding source, assessment tools and trial commencement year. A p < 0.05 was considered statistically significance. Results: Of the 335 trial protocols (non-small cell (87.2%) and small cell (12.8%)), most were from Europe (50.4%). The trial lead investigator was from industry (56.7%) followed by academia (25.1%). Allied health professional involvement was minimal (0.6%). Trial protocols mostly recorded overall survival (96.4%) and toxicity (83.9%). However, physical activity, weight/BMI, dysphagia, dyspnoea and oral mucositis were recorded in <30%, with dietary limitations, caloric intake and lean muscle mass recorded in <3% of the trials. Measures and symptoms were not associated with cancer type. Trial location was associated with the measures toxicity, physical activity and caloric intake and all symptoms. Lead investigator was associated with the measures toxicity and weight/BMI and all symptoms except for dyspnoea. Performance status and assessment tools were mentioned in 93.4% and 41.8% of the trials, respectively, with significant associations between assessment tools and outcomes, except for weight/BMI, dietary limitations, lean muscle mass, dysphagia and oral mucositis. There was a significant trend with trial commencement year for the measures physical activity (p = 0.002) and weight/BMI (p = 0.000) and all symptoms, except for appetite loss (p = 0.115) and pain (p = 0.433). Conclusions: While the reporting of measures and outcomes was generally higher compared to gastrointestinal chemotherapy cancer trials, it still faced significant under-reporting. Assessment tools should include cachexia-specific symptoms to accurately assess the quality of life in patients with lung cancer undergoing chemotherapy clinical trials. Full article

(This article belongs to the Special Issue Advances in Clinical Trials: Outcome, Innovations, Challenges, and Ethical Practice in Cancer Research 2025–2026)

► Show Figures

Figure 1

12 pages, 596 KB

Open AccessArticle

Design of a Phase I Drug Combination Study with Adaptive Allocation Based on Dose-Limiting Toxicity Attribution

by Nolan A. Wages, Bethany J. Horton, Li Liu, Enrica Marchi and Gina R. Petroni

Cancers 2025, 17(6), 1038; https://doi.org/10.3390/cancers17061038 - 20 Mar 2025

Cited by 1 | Viewed by 2308

Abstract

Background: This article describes the adaptation of a Phase I drug combination method to incorporate dose-limiting toxicity (DLT) attribution in dose assignments. The study is motivated by the Embolden trial (NCT03240211), a Phase Ib, multicenter trial at the UVA Comprehensive Cancer Center evaluating pembrolizumab with pralatrexate (Arm A), decitabine (Arm C), or both (Arm B) in relapsed/refractory peripheral and cutaneous T cell lymphomas. Methods: While Arms A and C used monotherapy dose escalation, Arm B required simultaneous escalation of both agents, integrating drug-specific DLT attribution to guide dosing. Results: We adapted the partial order continual reassessment method (POCRM) to incorporate this attribution, ensuring appropriate de-escalation of the offending agent. Given the trial’s complexity, software modifications were necessary to evaluate design performance through simulations. Conclusions: This work underscores the importance of novel dose-finding strategies in early-phase trials and aims to promote their broader adoption for improved trial efficiency and transparency. Full article

(This article belongs to the Special Issue Advances in Clinical Trials: Outcome, Innovations, Challenges, and Ethical Practice in Cancer Research 2025–2026)

► Show Figures

Figure 1

Review

Jump to: Research, Other

27 pages, 932 KB

Open AccessReview

Cancer Prevention Clinical Trials: Advances and Challenges

by Elizabeth R. Francis, Farzeen Z. Syed, Arun Rajan and Eva Szabo

Cancers 2026, 18(3), 390; https://doi.org/10.3390/cancers18030390 - 27 Jan 2026

Viewed by 1069

Abstract

Prevention of cancer is an appealing strategy to reduce the burden of illness associated with cancer, but despite the rapidly advancing understanding of the early phases of carcinogenesis, translation of biologic insights into actionable public health strategies has been challenging. Phase III clinical trials have historically required large numbers of participants and lengthy durations to show effects in the minority of participants who develop cancer during the finite span of each trial. Early-phase trials help to refine intervention strategies and provide preliminary human safety and efficacy data to justify phase III trials. Recent advances in trial methodology and developments in immunopreventive strategies have energized the field of cancer prevention and provide potential paths for prevention of multiple cancer types. In this review we discuss the history and current state of cancer prevention trials, with a focus on overcoming inherent biologic and methodologic barriers to preventive agent development. Full article

(This article belongs to the Special Issue Advances in Clinical Trials: Outcome, Innovations, Challenges, and Ethical Practice in Cancer Research 2025–2026)

► Show Figures

Graphical abstract

12 pages, 1593 KB

Open AccessEditor’s ChoiceReview

Next-Generation CAR-T and TCR-T Cell Therapies for Solid Tumors: Innovations, Challenges, and Global Development Trends

by Tomomi Sanomachi, Yuki Katsuya, Tetsuya Nakatsura and Takafumi Koyama

Cancers 2025, 17(12), 1945; https://doi.org/10.3390/cancers17121945 - 11 Jun 2025

Cited by 15 | Viewed by 12001

Abstract

Chimeric antigen receptor (CAR)-T and T-cell receptor (TCR)-engineered T-cell (TCR-T) therapies have revolutionized the treatment of hematological malignancies; however, their application to solid tumors remains a formidable challenge. The immunosuppressive tumor microenvironment, antigen heterogeneity, and manufacturing complexity limit the clinical efficacy and scalability of these treatment modalities. This review provides a comprehensive analysis of the current clinical development strategies for CAR-T and TCR-T cell therapies for solid tumors. Herein, we discuss recent breakthroughs and highlight the potential of TCR-T cell therapy. Furthermore, innovative approaches for enhancing CAR-T cell function in solid tumors (e.g., in vivo engineering; induced pluripotent stem cell-derived allogeneic CAR-T cells; armored CAR constructs; dual-antigen targeting; and combination regimens with checkpoint inhibitors, chemotherapy, radiotherapy, and oncolytic viruses) are explored. We also present trends in global patent activity, revealing a marked acceleration in CAR-T- and TCR-T-related innovations, with the United States and China leading with respect to application volumes. This field is increasingly characterized by multidisciplinary collaborations between academia and industry, driving the development of next-generation platforms, including messenger RNA-based and off-the-shelf cell therapies. Although no CAR-T product has been approved for solid tumors, these findings underscore the accelerating momentum and translational promise of adoptive cell therapies. Addressing the unique biological and logistical challenges of solid tumors is essential for realizing the full potential of these transformative immunotherapies. Full article

(This article belongs to the Special Issue Advances in Clinical Trials: Outcome, Innovations, Challenges, and Ethical Practice in Cancer Research 2025–2026)

► Show Figures

Figure 1

20 pages, 617 KB

Open AccessReview

Advancements in Electronic Medical Records for Clinical Trials: Enhancing Data Management and Research Efficiency

by Mingyu Lee, Kyuri Kim, Yoojin Shin, Yoonji Lee and Tae-Jung Kim

Cancers 2025, 17(9), 1552; https://doi.org/10.3390/cancers17091552 - 2 May 2025

Cited by 15 | Viewed by 10892

Abstract

Recent advancements in electronic medical records (EMRs) have transformed clinical trials and healthcare systems by improving data accuracy, regulatory compliance, and integration with decision support tools. These innovations enhance trial efficiency, streamline patient recruitment, and enable large-scale data analysis while bridging clinical practice with research. Despite these benefits, challenges such as data standardization, privacy concerns, and usability issues persist. Overcoming these barriers through policy reforms, technological innovations, and robust methodologies is essential to maximizing the potential of EMRs. We examine current developments, challenges, and future directions for optimizing EMRs in clinical trials and healthcare delivery. Full article

(This article belongs to the Special Issue Advances in Clinical Trials: Outcome, Innovations, Challenges, and Ethical Practice in Cancer Research 2025–2026)

► Show Figures

Figure 1

Other

Jump to: Research, Review

12 pages, 2402 KB

Open AccessSystematic Review

Interventional Clinical Trials in Metastatic Pulmonary Large-Cell Neuroendocrine Carcinoma: A Systematic Review of Prospective, Interventional Trials

by Elettra Merola, Maria Pina Dore and Giuseppe Fanciulli

Cancers 2026, 18(6), 964; https://doi.org/10.3390/cancers18060964 - 17 Mar 2026

Viewed by 445

Abstract

Background/Objectives: Pulmonary neuroendocrine neoplasms comprise a heterogeneous group of epithelial lung tumors characterized by varying degrees of differentiation and biological aggressiveness. Among high-grade types, large cell neuroendocrine carcinoma (LCNEC) is an uncommon but clinically significant entity, representing approximately 3% of lung cancers, with the optimal first-line therapeutic approach remaining uncertain. Our aim was to evaluate the available prospective therapeutic evidence in patients with advanced or metastatic pulmonary LCNEC, defining the current evidence and identifying key gaps to inform future research. Methods: A systematic literature search was conducted using PubMed, Scopus, and Web of Science (last update: 9 August 2025). Endpoints included the evaluation of clinical outcomes from interventional trials and safety. Results: Overall, 2139 records were identified through the database search and handsearching. After removal of duplicates and non-eligible records, only 4 prospective, non-randomized studies were eligible for the systematic review. Due to the risk of bias and substantial methodological variability, a meta-analysis could not be reliably performed. Three trials investigated first-line platinum-based chemotherapy regimens, while only one study evaluated immunotherapy in lung LCNEC. Overall clinical outcomes were modest, with benefits appearing limited in duration, with median PFS consistently <6 months and median OS rarely exceeding one year. Conclusions: The findings of this review underscore a persistent and substantial evidence gap in the management of advanced pulmonary LCNEC. Closing this gap will require coordinated international collaborations and innovative trial designs, including molecular analysis as a driver for patient management. Without such efforts, the prospect of personalized medicine for lung LCNEC will remain far from reality. Full article

(This article belongs to the Special Issue Advances in Clinical Trials: Outcome, Innovations, Challenges, and Ethical Practice in Cancer Research 2025–2026)

► Show Figures

Journal Menu

Journal Browser

Advances in Clinical Trials: Outcome, Innovations, Challenges, and Ethical Practice in Cancer Research 2025–2026

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (9 papers)

Research

Review

Other

Further Information

Guidelines

MDPI Initiatives

Follow MDPI