NG11-2-P1b
Research type
Research Study
Full title
A Phase-1b Dose Escalation Study to Assess the Effect of NG11-2 on Radiation Induced Oral Mucositis in Patients with Head & Neck Cancer
IRAS ID
1004528
Contact name
Gary Bower
Contact email
Sponsor organisation
VasoDynamics Ltd
Eudract number
2022-002409-99
ISRCTN Number
ISRCTN87831050
Research summary
The purpose of the study is to investigate the effect of a new formulation of adrenaline (named NG11-2) in the reduction of severe Radiation-induced Oral Mucositis (RIOM). Severe RIOM is a debilitating side-effect of radiotherapy among patients receiving high dose radiation therapy on the head and neck area for head and neck cancer treatment. Severe RIOM can lead to increased hospital care and is often a dose-limiting factor and cause of radiotherapy interruption and, as a result, leads to a sub-optimal anti-cancer efficacy. There are no approved drugs currently available for prevention & treatment of severe RIOM and care for these patients is primarily supportive.
The study is a Phase-1b dose escalation , multi-centre study of NG11-2 in the reduction of severe RIOM in Head and Neck cancer patients undergoing radiotherapy, with or without concurrent chemotherapy. Patients will be enrolled at escalating dose levels and once a suitable dose level has been identified, a further cohort of patients will be enrolled at the Recommended Phase-2 Dose (RP2D).Daily treatment with NG11-2 will occur prior to radiotherapy for 5 days/week for up to 7 weeks. Throughout the radiotherapy regimen, no more than 60 minutes prior to the completion of radiotherapy, on each weekday the patient will be instructed to
a) rinse their mouth twice with room temperature water in the 5 minutes prior to NG11-2 treatment then
b) rinse their mouth with 12.5ml of NG11-2 for between 90 & 120 seconds duration, gargling twice for approximately three seconds each if possible during this period then
c) expectorate the solutionTreatment will continue for up to 7 weeks with a 6-week follow-up period.
LAY SUMMARY OF STUDY RESULTS:
This study was Sponsored and funded by VasoDynamics Ltd (a biotechnology company based in the UK) and involved hospitals in 5 UK locations (2 England, 2 Scotland, 1 Northern Ireland). A total of 15 patients with newly diagnosed Head and Neck cancer undergoing a variety of treatments involving radiotherapy, were enrolled into the study.The purpose of this study was to investigate whether a novel investigational pharmaceutical product (codenamed NG11-2) is well-tolerated and could be used to prevent the development of severe oral mucositis (mouth ulceration) in patients undergoing cancer treatment involving high-dose radiation to their mouth cavity. Severe oral mucositis is a debilitating side-effect of radiotherapy, for which there is currently no preventative medicine available.
Each enrolled patient received the NG11-2 study drug as a mouthwash a few minutes before each of their daily radiotherapy sessions, until the completion of the radiotherapy treatment, typically for up to 7 weeks.
Four dose-levels of mouthwash were tested in the first part and all were well tolerated. The highest dose was then given to an additional 7 patients. No serious side-effects related to the NG11-2 mouthwash were reported and NG11-2 mouthwash was considered well tolerated in this study.
The mouthwash showed positive preliminary results with the incidence of severe oral mucositis being reduced to 44% at the highest dose compared to 64 74% in the control groups reported in the literature. The median duration of severe oral mucositis was also reduced from 18-19 days reported in the literature to 15.5 days at the highest dose of NG11-2.
LAY SUMMARY OF STUDY RESULTS:
This study involved hospitals in 5 UK locations (2 England, 2 Scotland, 1 Northern Ireland). A total of 15 patients being treated for Head and Neck cancer were enrolled into the study.
The purpose of this study was to investigate whether a novel investigational pharmaceutical product (codenamed NG11-2) was well tolerated at certain dose-levels and whether certain dose-level(s) could be used to prevent the development of severe oral mucositis (mouth ulceration) in patients with head and neck cancers undergoing treatments involving high-dose radiation to the mouth cavity. Severe oral mucositis (SOM) is a debilitating side effect of radiotherapy for which there is currently no preventative treatment available.
The study included a dose-escalation phase and a dose-expansion phase. Each enrolled patient received the study drug NG11-2 as a mouthwash a few minutes before each of their daily fractional radiotherapy, until completion of the whole radiotherapy treatment, typically for up to 7 weeks.
Four dose-levels of NG11-2 mouthwash were tested in the dose-escalation phase with two patients treated at each dose-level. After a Safety Committee assessment, the highest dose-level was chosen for the dose-expansion phase and was given to an additional 7 patients before the study completed.
The study’s primary endpoints were safety based and were assessed across both the dose-escalation phase and dose-expansion phase. The secondary endpoints of this study were preliminary efficacy endpoints, including the duration, incidence and time-to-onset of severe oral mucositis (SOM). The secondary endpoints were analysed on a total of 9 patients treated at the highest dose-level using the Kaplan-Meier approach, and the SOM scores were collected using the World Health Organisation (WHO) scale, Radiation Therapy Oncology Group (RTOG) scale and National Cancer Institute Common Toxicity Criteria Adverse Event (NCI-CTCAE) scale.
For the primary endpoint, no Dose-Limiting-Toxicity (DLT) was identified among the four dose-levels tested, and all dose-levels were considered well tolerated. There were no Serious Adverse Events reported relating to the NG11-2 product. The main local safety signal identified relating to NG11-2 was a “stinging” sensation in the mouth or some oral pain especially when there was co-occurrence of oral thrush. There was no correlation or pattern between the local signals identified and the dose-levels tested.
For the secondary endpoints results, the preliminary efficacy readouts based on WHO, RTOG and CTCAEv5 scales were:WHO scale:
Median duration of SOM was 15.5 days, compared to 18 to 19 days seen in published studies, presenting a notable reduction in SOM for participants with prophylactic NG11-2 treatment, including 2 participants who only received approximately half of the planned NG11-2 treatments.
Incidence of SOM was 44.4%, comparing to 64-74% in the control groups reported in the literature.
Median time-to-onset of SOM was 54.0 days;
RTOG scale:
Median duration of SOM was 14.0 days.
Incidence of SOM 33.3%.
Median time-to-onset of SOM could not be calculated because the probability of not reaching SOM was above 50% at the end of the reporting period.
CTCAEv5 scale:
Median duration of SOM was 17.0 days.
Incidence of SOM 33.3%.
Median time-to-onset of SOM was 54.0 days.
In conclusion, the results from this study support the continued development of NG11-2, and a further large-scale study is being planned to confirm whether NG11-2 can significantly reduce the incidence and duration of severe oral mucositis.
More information about the study can be found on the ISCRTN registry website (ISCRTN #87831050)"REC name
West Midlands - Coventry & Warwickshire Research Ethics Committee
REC reference
22/WM/0262
Date of REC Opinion
23 Jan 2023
REC opinion
Further Information Favourable Opinion