Clinical trial NCT01066741: Prevention of Radiation-induced Severe Oral Mucositis in Oral Cavity, Oropharynx, Hypopharynx, and Cavum Cancer
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Oropharynx Cancer
Hypopharynx Cancer
Keywords: Epidermoid carcinoma
Hypopharynx
Oropharynx
Oral cavity
Oral mucosa
Cavum
Severe Oral mucositis
Radiotherapy
Phytotherapy
Lead sponsor: Centre Leon Berard
Sponsor class: OTHER
Collaborators: name: BOIRON
First posted: 2010-02-10
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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).

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 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

Primary outcomes:
measure: Rate of occurrence of grade ≥ 3 (RTOG classification) mucositis during irradiation (only the first occurrence will be reported)
timeFrame: At the end of irradiation period (6 weeks)
Secondary outcomes:
measure: Rate of grade ≥2 mucositis
timeFrame: At the end of irradiation period (6 weeks)
measure: Rate of Mycosis and Herpes virus infection
timeFrame: At the end of irradiation period (6 weeks)
measure: Rate of use of symptomatic treatment in case of occurrence of mucositis
timeFrame: At the end of irradiation period (6 weeks)
measure: Rate and duration of radiation treatment interruption for toxicity
timeFrame: At the end of irradiation period (6 weeks)
measure: radiation dose, duration of grade ≥3 mucositis, maximum weight loss and maximum level of oral pain in case of grade ≥3 mucositis.
timeFrame: during the occurence of grade≥3 mucositis
measure: Treatment tolerance assessed through a satisfaction questionnaire, and evaluation of compliance
timeFrame: during medication administration
measure: Nutritional intake, estimated using caloric intake and the Detsky score, and rate of enteral and/or parenteral nutrition, in case of toxicity during irradiation
timeFrame: during the period of toxicity
measure: Rate of agreement between the radiation oncologist and the stomatologist for the detection of Grade ≥2 (RTOG classification) mucositis
timeFrame: At the end of irradiation period (6 weeks)
measure: Evaluation of the cost of severe mucositis treatment
timeFrame: during and until the end of severe mucositis treatment
Other outcomes:
Locations:
city: Lyon
country: France
facility: Centre Léon Bérard
Study officials:
affiliation: Centre Léon Bérard, LYON
name: Pascal POMMIER
role: PRINCIPAL_INVESTIGATOR
References:
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. doi: 10.1016/s0167-8140(02)00404-8.
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. doi: 10.1002/hed.10318.
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. doi: 10.1002/hed.20162.
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. doi: 10.1002/hed.10326.
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. French.
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. doi: 10.1002/14651858.CD001973.pub2.
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. doi: 10.1002/14651858.CD000978.pub2.
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. doi: 10.1016/S0360-3016(03)01627-4.
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. doi: 10.1200/JCO.2002.05.046.
citation: 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. doi: 10.1081/cnv-120016400.
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. doi: 10.1038/sj.bjc.6600824.
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. doi: 10.1016/s0360-3016(02)02935-8.
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. doi: 10.1016/s0360-3016(02)02890-0.
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. doi: 10.1002/1097-0142(20010815)92:43.0.co;2-1.
citation: Ertekin MV, Koc 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. doi: 10.1016/s0360-3016(03)01562-1.
citation: Maiche AG, Grohn P, Maki-Hokkonen H. Effect of chamomile cream and almond ointment on acute radiation skin reaction. Acta Oncol. 1991;30(3):395-6. doi: 10.3109/02841869109092392. No abstract available.
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. doi: 10.1002/(SICI)1097-0142(19960201)77:33.0.CO;2-6.