Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Apr 10;9(1):e86.
doi: 10.1017/cts.2025.65. eCollection 2025.

Characterization of terminated and withdrawn clinical trials for the treatment and prevention of oral mucositis

Alex Reznik  1 , Stephen Sonis  2   3   4 , Alessandro Villa  5   6
Affiliations

Characterization of terminated and withdrawn clinical trials for the treatment and prevention of oral mucositis

Alex Reznik et al. J Clin Transl Sci. .

Abstract

Purpose: Oral mucositis (OM) is a significant complication of cytotoxic cancer therapy and has no effective therapies. Unfortunately, the termination rate of clinical trials (CTs) testing potential OM interventions remains high. Here, we compared the characteristics of failed trials and matched completed trials to identify common features, which might inform better study design.

Methods: CTs for the prevention/treatment of OM were identified using ClinicalTrials.gov. Failed (terminated or withdrawn) trials were evaluated for phase, type of cancer treatment (radiotherapy, chemotherapy, or chemo-radiotherapy), subject accrual, study type, number of clinical sites, intervention type, inclusion criteria, sponsor type, and reason(s) for failure. A secondary analysis of completed OM CTs that were individually matched to failed trials based on indication and phase or intervention type served as a control.

Results: Failed OM CTs were more likely to have academic sponsorship (45.7% vs. 39.1%), nonrandomized design (19.6% vs. 4.3%), and lower mean subject accrual (27.8 subjects vs. 101.4 subjects) compared to completed trials. The leading reason for termination was recruitment/enrollment (37.9%). Recruitment/enrollment and safety/efficacy accounted for failure in 84.6% of phase II trials.

Conclusion: Contrary to general CTs where safety/efficacy concerns predominate, our results suggest OM-related trial failures are associated with a broader list of challenges including recruitment/enrollment, funding/sponsorship, and investigator/site issues. OM CTs demand aggressive planning, funding, and careful selection of trial sites and sponsorship to assure timely subject recruitment and reduce the risk for early termination and withdrawal.

Keywords: Oral mucositis; drug development; failed clinical trials; radiation therapy; supportive care.

PubMed Disclaimer

Conflict of interest statement

S Sonis is an employee of Biomodels, LLC and Primary Endpoint Solutions, LLC. Both companies assist industry, government and academics to study and enable drugs, biologicals, and devices to treat patients for a variety of indications including cancer and side effects and toxicities of its treatment. A Villa is a consultant for Merck, K Pharmaceuticals, Afyx Therapeutics, Lipella Pharmaceuticals, WSK Medical, and Primary Endpoint Solutions, LLC. A Villa receives research funding from Merck, MeiraGtx, and Mureva. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Figures

Figure 1.
Figure 1.
Summary of failed oral mucositis clinical trials by sponsorship and reason for failure. (A) Percentage of total failed oral mucositis (OM) clinical trials (CTs) by sponsor type. Failed trials are defined as terminated or withdrawn. (B) Percentage of failed OM CTs by reason for failure and CT phase. Total includes all 46 terminated or withdrawn CTs included in the study (phase I–IV and nonphase labeled studies). (C) Percentage of failed OM CTs by sponsor type and CT phase.
See this image and copyright information in PMC

References

    1. Villa A, Sonis ST. Mucositis: pathobiology and management. Curr Opin Oncol. May 2015;27(3):159–164. doi: 10.1097/cco.0000000000000180. - DOI - PubMed
    1. Epstein JB, Thariat J, Bensadoun RJ, et al. Oral complications of cancer and cancer therapy: from cancer treatment to survivorship. CA Cancer J Clin Nov-Dec. 2012;62(6)400–422. doi: 10.3322/caac.21157. - DOI - PubMed
    1. Iovoli AJ, Turecki L, Qiu ML, et al. Severe oral mucositis after intensity-modulated radiation therapy for head and neck cancer. JAMA Netw Open. 2023;6(10):e2337265. doi: 10.1001/jamanetworkopen.2023.37265. - DOI - PMC - PubMed
    1. Vagliano L, Feraut C, Gobetto G, et al. Incidence and severity of oral mucositis in patients undergoing haematopoietic SCT--results of a multicentre study. Bone Marrow Transplant. 2011;46(5):727–732. doi: 10.1038/bmt.2010.184. - DOI - PubMed
    1. Al-Ansari S, Zecha JA, Barasch A, de Lange J, Rozema FR, Raber-Durlacher JE. Oral mucositis induced by anticancer therapies. Curr Oral Health Rep. 2015;2(4):202–211. doi: 10.1007/s40496-015-0069-4. - DOI - PMC - PubMed

LinkOut - more resources