Abstract 1729TiP
Background
Clonidine MBT (Validive®) is an orally delivered prophylactic treatment for chemoradiotherapy (CRT)-induced severe oral mucositis (SOM) in patients with oropharyngeal cancer (OPC). Clonidine MBT is a novel, extended release formulation designed to adhere to the gums and dissolve slowly, releasing clonidine in the oral cavity over many hours. OPC occurs in the macrophages-rich regions at the back of the tongue and throat. CRT is used 1st line in OPC but tumor radiation also irradiates neighboring macrophages, inducing local expression of pro-inflammatory cytokines. These cytokines drive the oral mucosal ulcerations and pain leading to the functional limitations ithat characterize SOM. High salivary levels of cytokines correlate with mucositis severity. Clonidine is an α2-adrenoreceptor agonist. α2-adrenoreceptors are expressed by macrophages and mediate their expression of pro-inflammatory cytokines. Sustained delivery of clonidine in the oral cavity produced by clonidine MBT is thought to attenuate cytokine expression, reducing incidence of SOM. A previous phase II trial (BA2009/28/1) demonstrated a decreased incidence of CRT-induced SOM in OPC patients receiving clonidine MBT 100 μg. OPC patients treated with clonidine MBT 100 μg that developed SOM benefited from delayed onset and shorter duration. Patient-reported outcomes favored clonidine MBT 100 μg treated patients. Adverse events were similar in the clonidine MBT 100 ug group and placebo.
Trial design
VOICE is a randomized, blinded, placebo-controlled phase IIb/III trial to evaluate the effect of clonidine MBT on the incidence of SOM in patients with OPC. Rationale is presented under background. The trial follows a sequential design with an interim analysis after the phase IIb part of the trial. This will be performed by an IDMC, will evaluate safety and will provide the opportunity for a sample size re-estimation based on any observed treatment effects in the phase IIb. The complete study could enroll up to 260 patients. The first patient was randomized and received treatment in Feb. 2021. Approximately 50 US and EU sites are planned with completion of patient enrollment scheduled to finish in late 2022.
Clinical trial identification
NCT04648020.
Editorial acknowledgement
Legal entity responsible for the study
Monopar Therapeutics, Inc.
Funding
Monopar Therapeutics, Inc.
Disclosure
A.P. Mazar: Financial Interests, Personal and Institutional, Officer: Monopar Therapeutics, Inc. C.D. Robinson: Financial Interests, Personal and Institutional, Officer: Monopar Therapeutics, Inc. C.M. Starr: Financial Interests, Personal and Institutional, Member of the Board of Directors: Monopar Therapeutics, Inc. G. Layton: Financial Interests, Personal, Advisory Role: Monopar Therapeutics, Inc. P. Rioux: Financial Interests, Personal, Full or part-time Employment: Monopar Therapeutics, Inc.