Prevention of Radiation-induced Severe Oral Mucositis in Oral Cavity, Oropharynx, Hypopharynx, and Cavum Cancer

Oropharynx Cancer Clinical Trial

Official title:

Randomized Evaluation of a Phytopharmaceutical in Prevention of Severe Oral Mucositis in Patients Receiving Radiotherapy for Oral Cavity, Oropharynx, Hypopharynx, or Cavum Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01066741
• Other study ID #: HOMEODENT
• Secondary ID: ET2006-042
• Status: Terminated
• Phase: Phase 3
• First received: February 5, 2010
• Last updated: October 31, 2012
• Start date: May 2009
• Est. completion date: August 2011

Study information

• Verified date: October 2012
• Source: Centre Leon Berard
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the benefit of a mouthwash with a phytopharmaceutical preparation, Homeodent®, compared to a mouthwash solution containing sodium bicarbonate, for prevention of severe mucositis (grade ≥3, RTOG classification) in patients receiving irradiation for oral cavity, oropharynx, hypopharynx or cavum cancer.

This is a phase III, controlled, randomized, single blind study. The estimated inclusion period is approximately 24 months. The number of patients required in this monocentric study is 330 (165 per arm).

Description:

The standard treatment of oral cavity, oropharynx, hypopharynx, and cavum cancers is external radiotherapy. However, one of the associated toxicities is the occurrence of mucositis which can be a limiting factor in the treatment (dose reduction or treatment interruption can limit patient's survival), patient's quality of life decreases and severe complications can occur. The treatment of mucositis is mainly symptomatic; a randomized study has shown a benefit of a mouthwash with Benzydamine, a non steroidal anti-inflammatory drug, for patients receiving 50-Gy radiation. Another study with a lower number of patients has also shown a benefit of using a zinc sulfate solution. Boiron laboratories have developed a phytopharmaceutical preparation, Homeodent®, which has no secondary effects and which could prevent radiation-induced mucositis. This study will evaluate the efficiency of mouthwash with Homeodent® in a large randomized trial.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 78
• Est. completion date: August 2011
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• Male or female patient aged = 18 years

• ECOG PS = 2

• Patient with oral cavity and/or oropharynx and/or hypopharynx and/or cavum epidermoid carcinoma, whatever the stage

• Patient receiving a minimum radiation dose of 60 Gy

• Planned radiotherapy to at least 1/3 of the oral mucosa and/or oropharynx

• Mandatory affiliation with a health insurance system

• Signed, written informed consent

Exclusion Criteria:

• Previous irradiation to the oral mucosa and/or oropharynx

• Pre-existing mucositis

• Pregnant or lactating woman (negative serum or urinary pregnancy test for women with child-bearing potential)

• Patient included in another study including experimental radiotherapy possibly toxic to the mucosa

• difficult follow up of the patient

• patient deprived of civil rights

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Hypopharynx Cancer
• Mucositis
• Oropharynx Cancer
• Stomatitis

Intervention

Drug:
• Homeodent®
Two-minute mouthwash with 5 ml of solution diluted in 125 ml of water, 3 times per day after meals and tooth brushing.
• 1.4% Sodium Bicarbonate solution
Two-minute mouthwash with 125 ml of solution, 3 times per day after meals and tooth brushing

Locations

Country	Name	City	State
France	Centre Léon Bérard	Lyon

Sponsors (2)

Lead Sponsor	Collaborator
Centre Leon Berard	BOIRON

Country where clinical trial is conducted

France, 

References & Publications (17)

Dodd MJ, Miaskowski C, Greenspan D, MacPhail L, Shih AS, Shiba G, Facione N, Paul SM. Radiation-induced mucositis: a randomized clinical trial of micronized sucralfate versus salt & soda mouthwashes. Cancer Invest. 2003;21(1):21-33. — View Citation

Duncan GG, Epstein JB, Tu D, El Sayed S, Bezjak A, Ottaway J, Pater J; National Cancer Institute of Canada Clinical Trials Group. Quality of life, mucositis, and xerostomia from radiotherapy for head and neck cancers: a report from the NCIC CTG HN2 randomized trial of an antimicrobial lozenge to prevent mucositis. Head Neck. 2005 May;27(5):421-8. — View Citation

El-Sayed S, Nabid A, Shelley W, Hay J, Balogh J, Gelinas M, MacKenzie R, Read N, Berthelet E, Lau H, Epstein J, Delvecchio P, Ganguly PK, Wong F, Burns P, Tu D, Pater J. Prophylaxis of radiation-associated mucositis in conventionally treated patients with head and neck cancer: a double-blind, phase III, randomized, controlled trial evaluating the clinical efficacy of an antimicrobial lozenge using a validated mucositis scoring system. J Clin Oncol. 2002 Oct 1;20(19):3956-63. — View Citation

Epstein JB, Silverman S Jr, Paggiarino DA, Crockett S, Schubert MM, Senzer NN, Lockhart PB, Gallagher MJ, Peterson DE, Leveque FG. Benzydamine HCl for prophylaxis of radiation-induced oral mucositis: results from a multicenter, randomized, double-blind, placebo-controlled clinical trial. Cancer. 2001 Aug 15;92(4):875-85. — View Citation

Ertekin MV, Koç M, Karslioglu I, Sezen O. Zinc sulfate in the prevention of radiation-induced oropharyngeal mucositis: a prospective, placebo-controlled, randomized study. Int J Radiat Oncol Biol Phys. 2004 Jan 1;58(1):167-74. — View Citation

Fidler P, Loprinzi CL, O'Fallon JR, Leitch JM, Lee JK, Hayes DL, Novotny P, Clemens-Schutjer D, Bartel J, Michalak JC. Prospective evaluation of a chamomile mouthwash for prevention of 5-FU-induced oral mucositis. Cancer. 1996 Feb 1;77(3):522-5. — View Citation

Lapeyre M, Charra-Brunaud C, Kaminsky MC, Geoffrois L, Dolivet G, Toussaint B, Maire F, Pourel N, Simon M, Marchal C, Bey P. [Management of mucositis following radiotherapy for head and neck cancers]. Cancer Radiother. 2001 Nov;5 Suppl 1:121s-130s. Review. French. — View Citation

Maiche AG, Gröhn P, Mäki-Hokkonen H. Effect of chamomile cream and almond ointment on acute radiation skin reaction. Acta Oncol. 1991;30(3):395-6. — View Citation

Saarilahti K, Kajanti M, Joensuu T, Kouri M, Joensuu H. Comparison of granulocyte-macrophage colony-stimulating factor and sucralfate mouthwashes in the prevention of radiation-induced mucositis: a double-blind prospective randomized phase III study. Int J Radiat Oncol Biol Phys. 2002 Oct 1;54(2):479-85. — View Citation

Scully C, Epstein J, Sonis S. Oral mucositis: a challenging complication of radiotherapy, chemotherapy, and radiochemotherapy. Part 2: diagnosis and management of mucositis. Head Neck. 2004 Jan;26(1):77-84. Review. — View Citation

Scully C, Epstein J, Sonis S. Oral mucositis: a challenging complication of radiotherapy, chemotherapy, and radiochemotherapy: part 1, pathogenesis and prophylaxis of mucositis. Head Neck. 2003 Dec;25(12):1057-70. Review. — View Citation

Stokman MA, Spijkervet FK, Burlage FR, Dijkstra PU, Manson WL, de Vries EG, Roodenburg JL. Oral mucositis and selective elimination of oral flora in head and neck cancer patients receiving radiotherapy: a double-blind randomised clinical trial. Br J Cancer. 2003 Apr 7;88(7):1012-6. — View Citation

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. Review. — View Citation

Trotti A, Garden A, Warde P, Symonds P, Langer C, Redman R, Pajak TF, Fleming TR, Henke M, Bourhis J, Rosenthal DI, Junor E, Cmelak A, Sheehan F, Pulliam J, Devitt-Risse P, Fuchs H, Chambers M, O'Sullivan B, Ang KK. A multinational, randomized phase III trial of iseganan HCl oral solution for reducing the severity of oral mucositis in patients receiving radiotherapy for head-and-neck malignancy. Int J Radiat Oncol Biol Phys. 2004 Mar 1;58(3):674-81. — View Citation

Warde P, O'Sullivan B, Aslanidis J, Kroll B, Lockwood G, Waldron J, Payne D, Bayley A, Ringash J, Kim J, Liu FF, Maxymiw W, Sprague S, Cummings BJ. A Phase III placebo-controlled trial of oral pilocarpine in patients undergoing radiotherapy for head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2002 Sep 1;54(1):9-13. — View Citation

Worthington HV, Clarkson JE, Eden OB. Interventions for preventing oral mucositis for patients with cancer receiving treatment. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD000978. Review. Update in: Cochrane Database Syst Rev. 2007;(4):CD000978. — View Citation

Worthington HV, Clarkson JE, Eden OB. Interventions for treating oral mucositis for patients with cancer receiving treatment. Cochrane Database Syst Rev. 2004;(2):CD001973. Review. Update in: Cochrane Database Syst Rev. 2007;(2):CD001973. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of occurrence of grade = 3 (RTOG classification) mucositis during irradiation (only the first occurrence will be reported)		At the end of irradiation period (6 weeks)	No
Secondary	Rate of grade =2 mucositis		At the end of irradiation period (6 weeks)	No
Secondary	Rate of Mycosis and Herpes virus infection		At the end of irradiation period (6 weeks)	No
Secondary	Rate of use of symptomatic treatment in case of occurrence of mucositis		At the end of irradiation period (6 weeks)	No
Secondary	Rate and duration of radiation treatment interruption for toxicity		At the end of irradiation period (6 weeks)	Yes
Secondary	radiation dose, duration of grade =3 mucositis, maximum weight loss and maximum level of oral pain in case of grade =3 mucositis.		during the occurence of grade=3 mucositis	No
Secondary	Treatment tolerance assessed through a satisfaction questionnaire, and evaluation of compliance		during medication administration	No
Secondary	Nutritional intake, estimated using caloric intake and the Detsky score, and rate of enteral and/or parenteral nutrition, in case of toxicity during irradiation		during the period of toxicity	No
Secondary	Rate of agreement between the radiation oncologist and the stomatologist for the detection of Grade =2 (RTOG classification) mucositis		At the end of irradiation period (6 weeks)	No
Secondary	Evaluation of the cost of severe mucositis treatment		during and until the end of severe mucositis treatment	No