Efficacy and Safety of FORRAD® for the Management of Radiation-induced Mucositis in Patients With Nasopharyngeal Carcinoma Receiving IMRT

Nasopharyngeal Neoplasms Clinical Trial

Official title:

Efficacy and Safety of FORRAD® for the Management of Radiation-induced Mucositis in Patients With Nasopharyngeal Carcinoma Receiving IMRT: A Single-center, Randomized Controlled Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02735317
• Other study ID #: B2015-074-01
• Status: Not yet recruiting
• Phase: Phase 2
• First received: March 27, 2016
• Last updated: April 6, 2016
• Start date: April 2016
• Est. completion date: June 2017

Study information

• Verified date: April 2016
• Source: Sun Yat-sen University
• Contact: Yun-fei Xia, M.D.
• Phone: +86-20-87343096
• Email: xiayf[@]sysucc.org.cn
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Radiation therapy remains the principal treatment for nasopharyngeal carcinoma (NPC). The most frequently occurred radiation-related side effect is probably the radiation-induced oral mucositis (OM), which affects up to 100% of NPC patients receiving radiation therapy. When severe, oral mucositis increases the risk of infection and may compromise clinical outcomes by necessitating treatment breaks, dosage reductions, and reduced therapy compliance. In China, a quadruple mixture, composed of dexamethasone, gentamicin, vitamin B12, and procaine, is commonly prescribed when NPC patients begin to suffer from radiation-induced OM. However, the incidence of radiation-induced OM is still quite high. Oral Ulcer Gargle (FORRAD®) is a proprietary viscous liquid mucoadhesive hydrogel formulation. It creates a palliative barrier over injured mucosa, to prevent and to cure radiation-induced OM. The objective of this randomized phase II study is to assess the efficacy and safety of Oral Ulcer Gargle (FORRAD®) as an intervention for radiation-induced OM in the treatment of NPC, compared with the commonly used quadruple mixture, which is composed of dexamethasone, gentamicin, vitamin B12, and procaine.

Description:

Nasopharyngeal carcinoma (NPC) is one of the most common malignances in South China. Radiation therapy remains the principal treatment for NPC. The most frequently occurred radiation-related side effect is probably the radiation-induced oral mucositis (OM), which affects up to 100% of NPC patients receiving radiation therapy. Although intensity modulated radiation therapy (IMRT) has been widely used in China nowadays, the incidence of radiation-induced oral mucositis is still high. OM can decrease patients' oral intake and nutrition, leading to dehydration, weight loss, and declining performance status that may require intravenous fluid hydration, feeding tube placement, and hospitalization. OM also may increase opioid use. When severe, oral mucositis increases the risk of infection and may compromise clinical outcomes by necessitating treatment breaks, dosage reductions, and reduced therapy compliance. Common clinical management strategies include bland rinses, topical anesthetics and analgesics, mucosal coating agents, and systemic analgesics. However, none of these interventions has been supported by conclusive evidence. In China, a quadruple mixture, composed of dexamethasone, gentamicin, vitamin B12, and procaine, is commonly prescribed when NPC patients begin to suffer from radiation-induced OM.

Oral Ulcer Gargle (FORRAD®) is a proprietary viscous liquid mucoadhesive hydrogel formulation. It creates a palliative barrier over injured mucosa, to prevent and to cure radiation-induced OM.

The objective of this randomized phase II study is to assess the efficacy and safety of Oral Ulcer Gargle (FORRAD®) as an intervention for radiation-induced OM in the treatment of NPC, compared with the commonly used quadruple mixture, which is composed of dexamethasone, gentamicin, vitamin B12, and procaine.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 90
• Est. completion date: June 2017
• Est. primary completion date: June 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Pathologically confirmed and previously untreated nasopharyngeal carcinoma.

2. Age = 18 years and = 65 years.

3. Karnofsky performance status (KPS) score = 70.

4. Planned to receive radiotherapy alone or concurrent chemoradiotherapy, with intensity-modulated radiation therapy (IMRT).

5. Adequate bone marrow function: while blood cell >= 3,000/µL, absolute neutrophil count >= 1,500/µL, hemoglobin >= 100g/L, platelet >= 75,000/µL.

6. Life expectancy of >= 3 months.

Exclusion Criteria:

1. Known allergic reaction to any component of Oral Ulcer Gargle (FORRAD®) or quadruple mixture, which is composed of dexamethasone, gentamicin, vitamin B12, and procaine, or severe allergic constitution.

2. Other conditions that the investigators consider as inappropriate for enrolling into this study.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Mucositis
• Nasopharyngeal Neoplasms
• Stomatitis

Intervention

Drug:
• Oral Ulcer Gargle (FORRAD®)
Oral Ulcer Gargle (FORRAD®) is prescribed at the beginning of radiotherapy for free. Patients are asked to start application of Oral Ulcer Gargle (FORRAD®) at the onset of radiotherapy, four times a day (after meals and before bedtime), until completion of their radiotherapy. All patients will receive conventional health education and medical care for prevention and treatment of radiation-induced oral mucositis. When grade > 3 OM happened, other interventions, such as prophylactic or therapeutic antibacterial therapy, will be used, and radiotherapy should be interrupted.
• Quadruple mixture, composed of dexamethasone, gentamicin, vitamin B12, and procaine
Quadruple mixture is prescribed at the beginning of radiotherapy. Patients are asked to start application of quadruple mixture at the onset of radiotherapy, four times a day (before meals and before bedtime), until completion of their radiotherapy. All patients will receive conventional health education and medical care for prevention and treatment of radiation-induced oral mucositis. When grade > 3 OM happened, other interventions, such as prophylactic or therapeutic antibacterial therapy, will be used, and radiotherapy should be interrupted.

Locations

Country	Name	City	State
China	Department of Radiation Oncology, Sun Yat-Sen University Cancer Center	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Yun-fei Xia

Country where clinical trial is conducted

China, 

References & Publications (11)

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Chen L, Hu CS, Chen XZ, Hu GQ, Cheng ZB, Sun Y, Li WX, Chen YY, Xie FY, Liang SB, Chen Y, Xu TT, Li B, Long GX, Wang SY, Zheng BM, Guo Y, Sun Y, Mao YP, Tang LL, Chen YM, Liu MZ, Ma J. Concurrent chemoradiotherapy plus adjuvant chemotherapy versus concurrent chemoradiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma: a phase 3 multicentre randomised controlled trial. Lancet Oncol. 2012 Feb;13(2):163-71. doi: 10.1016/S1470-2045(11)70320-5. Epub 2011 Dec 7. — View Citation

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Mao YP, Yin WJ, Guo R, Zhang GS, Fang JL, Chi F, Qi ZY, Liu MZ, Ma J, Sun Y. Dosimetric benefit to organs at risk following margin reductions in nasopharyngeal carcinoma treated with intensity-modulated radiation therapy. Chin J Cancer. 2015 May 20;34(5):189-97. doi: 10.1186/s40880-015-0016-8. — View Citation

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Rodríguez-Caballero A, Torres-Lagares D, Robles-García M, Pachón-Ibáñez J, González-Padilla D, Gutiérrez-Pérez JL. Cancer treatment-induced oral mucositis: a critical review. Int J Oral Maxillofac Surg. 2012 Feb;41(2):225-38. doi: 10.1016/j.ijom.2011.10.011. Epub 2011 Nov 8. Review. — View Citation

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* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of grade = 3 mucositis	Incidence of grade = 3 mucositis according to CTCAE version 4.0	Day 56 after completion or termination of radiotherapy	No
Primary	OMAS	Oral Mucositis Assessment Scale (OMAS) provides an objective assessment of oral mucositis based on assessment of the appearance and extent of redness and ulceration in various areas of the mouth.	Day 56 after completion or termination of radiotherapy	No
Primary	OMDQ MTS question 2 (Q2) score	Oral Mucositis Daily Questionnaire (OMDQ) mouth and throat soreness (MTS) question 2 (Q2) is a 5-point categorical scale in which patients grade MTS from 0 (no soreness) to 4 (extreme soreness)3 which is a component of the OMDQ in that it tracks very well with objective (WHO score and opioid use) and subjective measurement of OM severity.	Day 56 after completion or termination of radiotherapy	No
Primary	WHO score	The World Health Organization (WHO) Oral Toxicity score combines both elements into a single score that grades the severity of the condition from 0 (no oral mucositis) to 4 (swallowing not possible such that patient needs supplementary nutrition).	Day 56 after completion or termination of radiotherapy	No
Primary	EORTC QLQ-C30	EORTC QLQ-C30 is a Quality-of-Life Instrument proposed by the European Organization for Research and Treatment of Cancer (EORTC), for use in International Clinical Trials in Oncology. The QLQ-C30 incorporates nine multi-item scales: five functional scales (physical, role, cognitive, emotional, and social); three symptom scales (fatigue, pain, and nausea and vomiting); and a global health and quality-of-life scale.	Day 56 after completion or termination of radiotherapy	No
Secondary	Interruption time during the schedule of radiotherapy	The cumulative interruption time during the schedule of radiotherapy because of grade 4 or higher radiation-induced oral mucositis.	Through radiotherapy completion or termination, an average of 7 weeks	No
Secondary	Time for healing of radiation-induced oral mucositis	Time until healing of radiation-induced oral mucositis, after the completion or the termination of radiotherapy.	Through study completion, an average of 15 weeks	No
Secondary	The cumulative dose of opioid used	The cumulative dose of opioid used from the beginning of radiotherapy until the completion of study.	Through study completion, an average of 15 weeks	No
Secondary	The cumulative time using opioid	The cumulative time using opioid from the beginning of radiotherapy until the completion of study.	Through study completion, an average of 15 weeks	No
Secondary	The change of body weight from baseline.	The change of body weight before radiotherapy and the day when radiotherapy is completed or terminated.	Baseline and 7 weeks	No