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

Purpose

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).

Condition	Intervention	Phase
Oropharynx Cancer Hypopharynx Cancer	Drug: Homeodent® Drug: 1.4% Sodium Bicarbonate solution	Phase 3

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

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Sodium bicarbonate

U.S. FDA Resources

Further study details as provided by Centre Leon Berard:

Primary Outcome Measures:

Rate of occurrence of grade ≥ 3 (RTOG classification) mucositis during irradiation (only the first occurrence will be reported) [ Time Frame: At the end of irradiation period (6 weeks) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Rate of grade ≥2 mucositis [ Time Frame: At the end of irradiation period (6 weeks) ] [ Designated as safety issue: No ]
Rate of Mycosis and Herpes virus infection [ Time Frame: At the end of irradiation period (6 weeks) ] [ Designated as safety issue: No ]
Rate of use of symptomatic treatment in case of occurrence of mucositis [ Time Frame: At the end of irradiation period (6 weeks) ] [ Designated as safety issue: No ]
Rate and duration of radiation treatment interruption for toxicity [ Time Frame: At the end of irradiation period (6 weeks) ] [ Designated as safety issue: Yes ]
radiation dose, duration of grade ≥3 mucositis, maximum weight loss and maximum level of oral pain in case of grade ≥3 mucositis. [ Time Frame: during the occurence of grade≥3 mucositis ] [ Designated as safety issue: No ]
Treatment tolerance assessed through a satisfaction questionnaire, and evaluation of compliance [ Time Frame: during medication administration ] [ Designated as safety issue: No ]
Nutritional intake, estimated using caloric intake and the Detsky score, and rate of enteral and/or parenteral nutrition, in case of toxicity during irradiation [ Time Frame: during the period of toxicity ] [ Designated as safety issue: No ]
Rate of agreement between the radiation oncologist and the stomatologist for the detection of Grade ≥2 (RTOG classification) mucositis [ Time Frame: At the end of irradiation period (6 weeks) ] [ Designated as safety issue: No ]
Evaluation of the cost of severe mucositis treatment [ Time Frame: during and until the end of severe mucositis treatment ] [ Designated as safety issue: No ]

Enrollment:	78
Study Start Date:	May 2009
Study Completion Date:	August 2011
Primary Completion Date:	February 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Homeodent® Mouthwash with Homeodent® is started on the first day of irradiation, then continued until the end of the irradiation period or until occurrence of grade ≥3 mucositis. In case of grade ≥3 mucositis, patients are instructed to mouthwash with Sodium Bicarbonate solution until complete disappearance of mucositis or until the end of irradiation.	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.
Active Comparator: 1.4 % Sodium Bicarbonate solution Mouthwash with sodium bicarbonate is started on the first day of irradiation, then continued until the end of the irradiation period. In case of grade ≥3 mucositis, mouthwash is continued until complete disappearance of the mucositis or until the end of irradiation. In both arms, after the end of irradiation, patients can receive treatment with Sodium Bicarbonate solution until complete disappearance of the mucositis.	Drug: 1.4% Sodium Bicarbonate solution Two-minute mouthwash with 125 ml of solution, 3 times per day after meals and tooth brushing

Arms

Assigned Interventions

Experimental: Homeodent®

Mouthwash with Homeodent® is started on the first day of irradiation, then continued until the end of the irradiation period or until occurrence of grade ≥3 mucositis. In case of grade ≥3 mucositis, patients are instructed to mouthwash with Sodium Bicarbonate solution until complete disappearance of mucositis or until the end of irradiation.

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.

Active Comparator: 1.4 % Sodium Bicarbonate solution

Mouthwash with sodium bicarbonate is started on the first day of irradiation, then continued until the end of the irradiation period. In case of grade ≥3 mucositis, mouthwash is continued until complete disappearance of the mucositis or until the end of irradiation.

In both arms, after the end of irradiation, patients can receive treatment with Sodium Bicarbonate solution until complete disappearance of the mucositis.

Drug: 1.4% Sodium Bicarbonate solution

Two-minute mouthwash with 125 ml of solution, 3 times per day after meals and tooth brushing

Detailed 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.

Eligibility

Ages Eligible for Study:	18 Years to 85 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01066741

Locations

France
Centre Léon Bérard
Lyon, France

Sponsors and Collaborators

Centre Leon Berard

BOIRON

Investigators

Principal Investigator:

Pascal POMMIER

Centre Léon Bérard, LYON

More Information

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. Review.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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. No abstract available.

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.

Responsible Party:	Centre Leon Berard
ClinicalTrials.gov Identifier:	NCT01066741 History of Changes
Other Study ID Numbers:	HOMEODENT, ET2006-042
Study First Received:	February 5, 2010
Last Updated:	October 31, 2012
Health Authority:	France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Centre Leon Berard:

Epidermoid carcinoma
Hypopharynx
Oropharynx
Oral cavity
Oral mucosa

Cavum
Severe Oral mucositis
Radiotherapy
Phytotherapy

Additional relevant MeSH terms:

Stomatitis
Oropharyngeal Neoplasms
Hypopharyngeal Neoplasms
Mucositis
Mouth Diseases
Stomatognathic Diseases
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms

Head and Neck Neoplasms
Neoplasms by Site
Neoplasms
Pharyngeal Diseases
Otorhinolaryngologic Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on May 21, 2013