Efficacy and Safety of CareMin650 for Prevention of Oral Mucositis in HNC Patients Starting Radiotherapy (PrOMiSE)

Efficacy and Safety of CareMin650 Used for the Prevention of Oral Mucositis in Patients With Head and Neck Cancer Starting Radiotherapy: the PrOMiSE Study

Oral mucositis (OM) can affect up to 90% of head and neck cancer (HNC) patients treated with radiation therapy (RT). The Mucositis Study Group of the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO) recommends the use of photobiomodulation (PBM) in the prevention of OM.

PBM is the application of lasers or non-coherent light sources such as LEDs, to beneficially influence cellular metabolism.

Even though PBM has proved its efficacy, this therapeutic option is currently limited by lack of standardization, accuracy and reproducibility. CareMin650 has been developed to overcome these issues, since it allows a reproducible delivery of light, independently of the operator. Additionally, it is easy to use and user-friendly.

PrOMiSE is a prospective, interventional, one-group, open-label, multicentric, international study conducted in European sites, specialized in radio-oncology.

Patients with head and neck cancer (HNC) starting RT and with no oral mucositis (OM) lesion at the time of inclusion, will be eligible. They will be treated by PBM using CareMin650 during the whole period of radiotherapy.

Study Overview

• Status: Completed
• Conditions: Head and Neck Cancer; Oral Mucositis (Ulcerative) Due to Radiation; Radiation Therapy Complication
• Intervention / Treatment: Device: Photobiomodulation

Detailed Description

Oral mucositis (OM) can affect up to 90% of head and neck cancer (HNC) patients treated with radiation therapy (RT) and/or chemotherapy (CT). It can be as severe as WHO grade 3 / 4 in 35% to more than 50% of cases. The pathobiology of OM relates to injuries that occur in the epithelial and connective tissues, as a response to a complex cascade of biological events, involving all the tissues and cellular elements of the mucosa (Sonis et al., 2004). OM may result in dysphagia, pain, risk of infection, weight loss, interruption or modification of anticancer therapy, or hospitalization.

As OM is a major and frequent side effect of RT, the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO) has published clinical practice guidelines for mucositis prevention secondary to cancer therapy. In addition to meticulous oral hygiene, MASCC/ISOO also suggests several therapeutic preventive strategies: growth factors, cytokines, anti-inflammatory agents, natural agents, … In the 2020 guidelines, photobiomodulation (PBM) formerly known as Low-Level Laser Therapy (LLLT), has obtain a full recommendation for the prevention of OM in patients undergoing RT, with or without concomitant CT, for HNC.

PBM is the application of lasers or non-coherent light sources such as LEDs, to beneficially influence cellular metabolism. In a Cochrane review that included 32 clinical trials, PBM was the only treatment that demonstrated a reduction in the risk of severe mucositis. In 2011, a meta-analysis included 11 placebo-controlled randomized trials in 415 patients treated with CT or RT for head and neck cancer (HNC) or hematopoietic stem cell transplantation. According to MASCC/ISOO recommendations, PBM is now recommended to prevent OM in HNC patients receiving RT with or without chemotherapy . The 2014 recommendations have been endorsed by the AFSOS (Association Française pour les Soins de Support en Oncologie) in France. Finally, the National Institute for Health and Care Excellence (NICE) determined that PBM for OM shows no major safety concerns and that evidence on efficacy is adequate in quality and quantity.

Taken together, these data show that PBM is an efficacious and safe option to prevent and/or treat radiotherapy-related OM.

Even though PBM has proved its efficacy, delivery of PBM in OM is currently limited by lack of standardization, accuracy and reproducibility. In particular, the distance between the lighting source and the mucosa or skin is difficult to assess and control accurately. Therefore, the amount of energy delivered may vary from one session to another, as well as from one operator to another.

CareMin650 has been developed to overcome these issues. CareMin650 allows a reproducible delivery of light, independently of the operator. As light is emitted by a flexible surface in contact with the mucosa or the skin, the dose delivered will be controlled. Additionally, it is meant to be easy to use and user-friendly. An interim analysis of SafePBM, a pilot study performed in France provided preliminary data on safety and efficacy. Among 186 CareMin650 sessions performed to prevent (n=152) or treat (n=34) OM in patients with HNC, no treatment-emergent adverse event was considered related to the device and no adverse event led to CareMin650 discontinuation. Only one out of 7 (14%) HNC patients treated in the preventative setting developed OM grade 3. However, this patient had started PBM 6 days after the initiation of RT, instead of starting at day 1 of RT. These encouraging results suggest that CareMin650 is both well tolerated and efficient to prevent severe OM in these high-risk patients.

The aim of the present study is to show the efficacy and safety of the CareMin650 medical device, in the prevention of severe OM in HNC patients receiving radiotherapy. The rate of severe OM will be compared to severe OM rate reported in the literature.

This is a prospective, interventional, one-group, open-label, multicentric, international study that will be conducted in Belgian and German sites, specialized in radio-oncology.

Photobiomodulation will be delivered to all included patients with the CareMin650 (NeoMedLight).

The studied Device CareMin 650 consists in a lightbox and a light applicator that delivers red light at 650nm to the oral mucosa and the neck. The applicator is composed of a connector, a fiberoptic beam of about 1 meter long and a light textile part. Appropriate non-sterile single use disposable sleeves will be added by the operator to cover the part in contact with the patient's mucosa or skin.

This device is CE marked and is used in this study in its intended indication.

No interim analysis is planned.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Aachen, Germany, 52074
    • UNIKLINIK RWTH AACHEN - Klinik für Radioonkologie und Strahlentherapie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ECOG (Eastern Cooperative Oncology Group) performance status ≤ 2.
• Histologically proven squamous cell carcinoma of oropharynx, hypo pharynx or oral cavity, with or without prior surgical resection.
• Starting intensity modulated radiation therapy (IMRT) or VoluMetric Arc Therapy (VMAT) on at least 50% of the oral mucosa at a total dose of at least 50 Gy, alone or associated with chemotherapy or targeted therapies.
• Dental examination prior to radiotherapy and any required dental treatment have been performed.

Exclusion Criteria:

• Any ongoing malignancy located in head or neck other than primary head and neck cancer (distant metastasis or extension).
• Any active cancer other than primary head and neck cancer.
• Only enteral/parenteral feeding or only liquid food intake are possible.
• Ongoing keratinocyte growth factors (palifermin) use.
• Known polyurethane allergy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Patient receiving Photobiomodulation

Device: Photobiomodulation; Oral pads will be applied on irradiated areas presenting a risk of radiotherapy-related OM. In addition, a derma pad will be applied on the anterior face of the neck to protect the oropharynx from OM. The dose to be delivered, at each session and each applied area, has been set at 3 J/cm². In case a lesion appears, the dose will be increased to 6J/cm² for curative treatment. Treatment with CareMin650 must start on the first day of radiotherapy and will be administered during the whole radiotherapy period, ideally 5 days/week, at least 3 days/week, ideally before the radiotherapy session.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients with at least one OM grade >2 at any time during radiotherapy.	To investigate the efficacy of CareMin650 in the prevention of oral mucositis in patients with HNC starting radiotherapy.	5-10 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of AE classified using MedDRA dictionary	To investigate the safety of CareMin650	5-10 weeks
Grading of AE using CTCAE V5	To investigate the safety of CareMin650	5-10 weeks
Number of patient with a temporary or sustains discontinuation of PBM due to AE	To investigate the safety of CareMin650	5-10 weeks
Time to OM lesions occurrence	To describe the patterns of OM lesions	5-10 weeks
Grade (WHO and CTCAE version 3) of OM lesions	To describe the patterns of OM lesions	5-10 weeks
Time to OM lesions resolution (defined as lesions that do not require further treatment)	To describe the patterns of OM lesions	5-10 weeks
Average duration of WHO grade 3 OM	To describe the duration of the grade 3 OM	5-10 weeks
Satisfaction of operators having use the device evaluated by a sponsor semi-quantitative satisfaction questionnaire.	To investigate the handling and the convenience of the device from the operator's perspective	Through study completion, an average of 1 year
Satisfaction of the patient having use the device evaluated by a sponsor semi-quantitative satisfaction questionnaire.	To investigate the patient satisfaction	Through patient study completion, an average of 2 months
Percentage of subject with onset of xerostomia during the study	To evaluate the evolution of xerostomia	5-10 weeks
Percentage of subject with onset of dysgeusia during the study	To evaluate the evolution of dysgeusia	5-10 weeks
Maximum severity of dysphagia as assessed by CTCAE V3	To evaluate the evolution of dysphagia	5-10 weeks
Evolution of body weight over time	To evaluate the evolution of body weight	5-10 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
For each neck dermatitis lesion: date of onset, location and CTCAE v5 grade	To estimate the incidence and severity of neck radiation dermatitis	5-10 weeks

Collaborators and Investigators

• Sponsor: NeoMedLight
• Collaborators: Monitoring Force Group
• Investigators: Principal Investigator: Michael J Elbe, MD

Publications and helpful links

General Publications

• Trotti A, Bellm LA, Epstein JB, Frame D, Fuchs HJ, Gwede CK, Komaroff E, Nalysnyk L, Zilberberg MD. Mucositis incidence, severity and associated outcomes in patients with head and neck cancer receiving radiotherapy with or without chemotherapy: a systematic literature review. Radiother Oncol. 2003 Mar;66(3):253-62. doi: 10.1016/s0167-8140(02)00404-8.
• Elad S, Cheng KKF, Lalla RV, Yarom N, Hong C, Logan RM, Bowen J, Gibson R, Saunders DP, Zadik Y, Ariyawardana A, Correa ME, Ranna V, Bossi P; Mucositis Guidelines Leadership Group of the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO). MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer. 2020 Oct 1;126(19):4423-4431. doi: 10.1002/cncr.33100. Epub 2020 Jul 28. Erratum In: Cancer. 2021 Oct 1;127(19):3700.
• Antunes HS, Herchenhorn D, Small IA, Araujo CMM, Viegas CMP, de Assis Ramos G, Dias FL, Ferreira CG. Long-term survival of a randomized phase III trial of head and neck cancer patients receiving concurrent chemoradiation therapy with or without low-level laser therapy (LLLT) to prevent oral mucositis. Oral Oncol. 2017 Aug;71:11-15. doi: 10.1016/j.oraloncology.2017.05.018. Epub 2017 Jun 3.
• Pulito C, Cristaudo A, Porta C, Zapperi S, Blandino G, Morrone A, Strano S. Oral mucositis: the hidden side of cancer therapy. J Exp Clin Cancer Res. 2020 Oct 7;39(1):210. doi: 10.1186/s13046-020-01715-7.

Study record dates

Study Major Dates

• Study Start (Actual): May 10, 2021
• Primary Completion (Actual): March 31, 2022
• Study Completion (Actual): June 30, 2022

Study Registration Dates

• First Submitted: December 22, 2020
• First Submitted That Met QC Criteria: January 6, 2021
• First Posted (Actual): January 7, 2021

Study Record Updates

• Last Update Posted (Actual): October 10, 2022
• Last Update Submitted That Met QC Criteria: October 6, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Head and Neck Cancer; Radiation Therapy; Photobiomodulation; Oral Mucositis
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Diseases; Gastroenteritis; Stomatognathic Diseases; Mouth Diseases; Head and Neck Neoplasms; Mucositis; Stomatitis
• Other Study ID Numbers: NML-20-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No