PROSpECT-PRIOR-2-CHEMO: PRIOR Dental Intervention Before Chemo to Reduce Chemotherapy Complications

Trial Title: PROSpECT-PRIOR-2-CHEMO: PRIOR Dental Intervention Before Chemo to Reduce Chemotherapy Complications

NCT ID: NCT06450821

Condition: Oncology
Periodontitis
Myeloma
Oral Mucositis
Febrile Neutropenia

Conditions: Official terms:
Mucositis
Periodontitis
Stomatitis
Neutropenia
Febrile Neutropenia

Study type: Interventional

Study phase: N/A

Overall status: Not yet recruiting

Study design:

Allocation: Randomized

Intervention model: Parallel Assignment

Intervention model description: The moderate and high-risk patients will then be randomised. Those randomised to the PRIOR intervention arm will be assessed in a consultant-led Restorative Dentistry department & treatment offered to stabilise primary dental diseases (periodontal disease, caries, and odontogenic infection). The treatment plan (by a dentist) will be delivered within the therapeutic window (the PRIOR window), defined as the period between MDT decision to offer ASCT/allo-SCT up to 7 days prior to commencement of CT for ASCT/allo-SCT. Participant treatment plans are highly personalised and therefore number of visits within the therapeutic window to deliver PRIOR are not strictly defined. PRIOR will aim to stabilise the oral health of the participant and remove obvious sources of oral health infection. Participant follow-up will monitor febrile event rate and OM incidence between groups, within the participant therapeutic window, defined as day one of SCT/CT+100 days.

Primary purpose: Supportive Care

Masking: None (Open Label)

Intervention:

Intervention type: Procedure
Intervention name: PRIOR [Proactive Intensive Oral Review & Treatment]
Description: Intervention Arm: Professional Oral Health Care (POHC) referred to as PRIOR [Proactive Intensive Oral Review & Treatment] prior to chemotherapy.
Arm group label: Intervention Arm

Summary: The aim of this feasibility trial is to determine if it is safe and feasible to treat oral health diseases in people with haematological cancers before they start their chemotherapy to reduce complications and disruption to planned chemotherapy dose or schedule.

Detailed description: PROSpECT PRIOR-2-CHEMO is a feasibility trial which will determine if it is safe and feasible to introduce a new oral health (OH) "PRIOR"(Pro-Active Intensive Oral Review and Treatment prior to chemotherapy) intervention for people with cancer, prior to receiving chemotherapy (CT). PRIOR is a novel interdisciplinary intervention that will be introduced into the current oncology pathway and mirrors the specialist Restorative Dental pathway for patients undergoing treatment for Head and Neck cancers. PRIOR is aimed to be delivered within the relatively short therapeutic window that oncology patients have before commencing their scheduled CT for 1) myeloma-ASCT, or 2) Haematological Allograft SCT . This feasibility phase is valuable to inform a definitive trial. The definitive trial would provide important efficacy and mechanistic understanding of the mitigation of CT adverse events (Aes), specifically life-threatening febrile episodes and painful oral mucositis (OM). The oral microbiome homeostasis is affected by CT; infection risk is exacerbated by OM, and other dental conditions like periodontal disease (PD) that damage the mucosa, caries, and acute / chronic odontogenic abscesses that collectively predispose to systemic translocation of oral-derived bacteria. With about 35% of the adult population affected by moderate and 10-15% severe periodontitis the importance of improving oral health and reducing bacteria load and portals of entry before CT is logical but seldom undertaken. Bacteria are responsible for the two most prevalent human oral biofilm-mediated diseases: dental caries and periodontitis. Periodontitis is a chronic disease caused by inflammatory reactions to gram negative anaerobic bacteria, resulting in irreversible destruction to oral hard and soft tissues. Local inflammation and tissue damage allow oral bacteria to enter the bloodstream. These Immunocompromised patients (such as those receiving CT) are highly susceptible to these invading pathogens which can manifest as life-threatening systemic infections. The risk of developing systemic infections may be associated with the severity of periodontitis (i.e. the total surface area of the ulcerated pocket epithelium) and the composition periodontal pocket microbiota composition. OM is also an inflammatory condition affecting the oral mucosa. OM is a CT-induced complication that not only affects patient's quality of life but also acts as a portal for oral microorganisms and inflammatory products to translocate into the systemic circulation via the ulcerated mucosa. Pre-existing poor oral and periodontal health is a significant risk factors for CT-induced febrile events, creating therapeutic opportunity. Oral infection, especially periodontitis, may affect the course and pathogenesis of a number of systemic diseases, including cancer, diabetes, and rheumatoid arthritis. The definitive trial will be a hypothesis-driven, mechanistic trial to understand the novel PRIOR intervention vs current NHS standard of care. Specifically, how PRIOR may mitigate Aes across a range of cancer types and CT regimens. The definitive aim is to understand how PRIOR impacts the oral microbial load, the portal entry sites, and the relationship between the oral microbiome, dysbiosis and systemic infection. The investigators will knowledge transfer from mechanistic evaluation of PD in rheumatoid arthritis showing the oral and gut microbiomes were perturbed but partly normalized after treatment. PD shares common mechanisms of action infection/inflammation across several systemic diseases. Clinical guidelines recommend seeking dental care prior to CT, this may include recommendation to seek dental care with a general dental practitioner (GDP, Primary care), but uptake is low and established care pathways are rare. Consequently, there has been little direct clinical observation by oncology teams of the value of including dental review; In part due to low advocacy by the oncology team, fuelled by little direct clinical observation of the value of including dental review. Patients report significant barriers to achieving dental care prior to CT including access to a GDP, lack of perceived need and logistical challenges. Patients do not prioritise seeking dental services as they are unaware of the potential importance to their oncology outcomes. The approach is to provide a specialist consultant-led hospital dental team review mirroring the specialist Restorative Dental pathway undertaken by patients having Head and Neck cancer treatment. Specialist dental teams within a secondary care setting may be better placed to deliver inter-disciplinary care than a GDP due to the time limited therapeutic window (therapeutic window defined as the period between diagnosis and deliver of CT). This work is the first to address the clinical need across several cancer patient groups.

Criteria for eligibility:
Criteria:
Inclusion Criteria (mod-high/risk trial participants): - Adults (≥ 18years) with scheduled Chemotherapy. Specifically, patients who meet the following diagnosis and treatment window requirements: - Myeloma- Autologous Stem Cell Transplantation (ASCT) before high-dose myeloablative CT. - Haematological cancers suitable for Allografts Stem Cell Transplant (SCT) before CT - Moderate / High Oral Health Risk Assessment - any one of the following: - Clinical evidence of caries (2+ teeth) - Clinical evidence on soft and hard tissue examination of infection, sinus, swelling or tenderness - BPE code 3-4 in any remaining sextant - BPE code 1-2 with >30% BOP - The patient is fully informed, has received PIS (patient information sheet) and considered during a 'cooling-off' period, is competent to consent, and is able to comply with minimum attendance requirements Exclusion Criteria: - Have a history of head and neck radiotherapy - Have been treated with Denusomab, Bevacizumab, Sunitinib or Aflibercept within 9 months of the MDT date. - Insufficient teeth [defined as <2] - Are incapable of providing informed written consent - Are unable to comply with minimum attendance requirements

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Dental Translational & Clinical Research Unit (DenTCRU)

Address:
City: Leeds
Zip: LS29LU
Country: United Kingdom

Contact:
Last name: Sue Pavitt, PhD

Phone: +44 7939 014659
Email: s.pavitt@leeds.ac.uk

Contact backup:
Last name: Nuria Navarro-Coy

Phone: +44 7967 786733
Email: n.navarro-coy@leeds.ac.uk

Investigator:
Last name: Zaid Ali, BChD
Email: Principal Investigator

Start date: July 2024

Completion date: October 2026

Lead sponsor:
Agency: University of Leeds
Agency class: Other

Collaborator:
Agency: The Leeds Teaching Hospitals NHS Trust
Agency class: Other

Source: University of Leeds

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06450821