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

NCT ID: NCT06450821

Last Updated: 2024-06-10

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-07-31
• Study Completion Date: 2026-10-31

Brief 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.

Conditions

Oncology; Periodontitis; Myeloma; Oral Mucositis; Febrile Neutropenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Study Groups

Control Arm

Control Arm: NHS standard care pathway delivered.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Intervention Arm

Intervention Arm: Professional Oral Health Care (POHC) referred to as PRIOR \[Proactive Intensive Oral Review \& Treatment\] prior to chemotherapy.

Group Type: EXPERIMENTAL

PRIOR [Proactive Intensive Oral Review & Treatment]

Intervention Type: PROCEDURE

Intervention Arm: Professional Oral Health Care (POHC) referred to as PRIOR \[Proactive Intensive Oral Review \& Treatment\] prior to chemotherapy.

Interventions

PRIOR [Proactive Intensive Oral Review & Treatment]

Intervention Arm: Professional Oral Health Care (POHC) referred to as PRIOR \[Proactive Intensive Oral Review \& Treatment\] prior to chemotherapy.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Leeds Teaching Hospitals NHS Trust

OTHER

Sponsor Role: collaborator

University of Leeds

OTHER

Sponsor Role: lead

Responsible Party

Sue Pavitt

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Zaid Ali, BChD

Role: PRINCIPAL_INVESTIGATOR

LTHT

Locations

Dental Translational & Clinical Research Unit (DenTCRU)

Leeds, West Yorkshire, United Kingdom

Countries

United Kingdom

Central Contacts

Sue H Pavitt, PhD

Role: CONTACT

s.pavitt@leeds.ac.uk

+44 7939 014 659

Anna Nielsen

Role: CONTACT

a.l.nielsen@leeds.ac.uk

+44 7948 776456

Facility Contacts

Sue Pavitt, PhD

Role: primary

s.pavitt@leeds.ac.uk

+44 7939 014659

Nuria Navarro-Coy

Role: backup

n.navarro-coy@leeds.ac.uk

+44 7967 786733

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Other Identifiers

296640

Identifier Type: -

Identifier Source: org_study_id