Study of a Copaiba-Based Mouthwash Combined With Low-Level Laser Therapy in the Prevention of Oral Mucositis in Patients Undergoing Hematopoietic Stem Cell Transplantation

NCT07810530 | Recruiting Phase 2

• 1 other identifier: 91924625.3.0000.5274
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 1

Brief Summary

Oral mucositis (OM) one of the most significant acute toxicity of Hematopoietic Stem Cell Transplantation (HSCT). There is already scientific evidence suporting OM the use of: low-level laser therapy (LLLT), cryotherapy (in autologous HSCT when conditioning regimens include high-dose melphalan), and keratinocyte growth factor (in autologous HSCT with high-dose chemotherapy associated with RT). In this sense, an alternative treatment becomes necessary. Based on the preliminary results of the phase I study, a double-blind, randomized phase II study is suggested to evaluate the effectiveness of copaiba-based mouthwash in the prevention of oral mucositis in HSCT was proposed. Patients will be randomized into 2 groups: A (copaíba) and B (placebo) and will use the mouthwash 4x/day. Each group will have 38 patients and be blind to the group in which they are included. They will be evaluated daily by a dental surgeon about oral mucositis, pain in the oral cavity and oropharynx, and dysphagia and will undergo daily laser therapy sessions, until neutropenic recovery.

Conditions

Oral Mucositis; Oral Mucositis Due to Chemotherapy; Oral Mucositis in Patients Undergoing HSCT; Oral Mucositis (Ulcerative) Due to Antineoplastic Therapy

Keywords

Oral mucositis; Hematopoietic Stem Cell Transplantation

Outcome Measures

Primary Outcomes (1)

• Safety and efficacy evaluation through adverse event related to the use of the product (Common Terminology Criteria for Adverse Events v5.0 and the Visual Analogic Scale)

  Evaluate the safety and efficacy of Copaiba mouthwash combined with LLLT in patients undergoing autologous Hematopoietic Stem Cell Transplantation by evaluating the occurrence of an adverse event related to the use of the product under investigation (pain 4 degrees above the Visual Analogic Scale score previously reported by the patient, nausea or vomiting for 7 consecutive days exclusively associated with the times of use of the mouthwash) The Common Terminology Criteria for Adverse Events v5.0 ranks the events from 1 to 5, with higher scores meaning worse outcome. The Visual Analogic Scale score ranks the eventos from 0 to 10, with higher scores meaning worse outcome.

  From the first day (day 1) of conditioning and continuing until engraftment (defined as the third consecutive day with neutrophil count ≥ 500 cells/mm³), approximately 28 days.

Secondary Outcomes (9)

• OM (World Health Organization scale)

  From the first day (day 1) of conditioning and continuing until engraftment (defined as the third consecutive day with neutrophil count ≥ 500 cells/mm³), approximately 28 days.

• OM ulcerated area (Sonis scale)

  From the first day (day 1) of conditioning and continuing until engraftment (defined as the third consecutive day with neutrophil count ≥ 500 cells/mm³), approximately 28 days.

• OM erythema area (Sonis scale)

  From the first day (day 1) of conditioning and continuing until engraftment (defined as the third consecutive day with neutrophil count ≥ 500 cells/mm³), approximately 28 days.

• OM (Sonis scale)

  From the first day (day 1) of conditioning and continuing until engraftment (defined as the third consecutive day with neutrophil count ≥ 500 cells/mm³), approximately 28 days.

• Oral pain

  From the first day (day 1) of conditioning and continuing until engraftment (defined as the third consecutive day with neutrophil count ≥ 500 cells/mm³), approximately 28 days.

Study Arms (2)

Copaíba

EXPERIMENTAL

Patients that will recieve Low-level laser therapy + copaiba mouthwash

Drug: Copaíba

Placebo

PLACEBO COMPARATOR

Patients that will recieve Low-level laser therapy + placebo mouthwash

Drug: Placebo

Interventions

Copaíba DRUG

An aqueous solution of copaíba (Copaifera Officinalis Resin) at 15% concentration will be used, manufactured by Interativo Pharmacy, according to the formula: copaíba oil (Copaifera Officinalis Resin) 15%, liquid mint aroma 5%, Tween 80 1%, aqueous solution (distilled water + Nipagin 0.1%) q.s.p. 100%. The product will be stored at room temperature and kept in the pharmacy of INCA. Patients will receive the solution once a week. They will be instructed to shake the bottle before use to homogenize the solution. They should use 10 mL of the solution per mouthwash (measured with the 10 mL dosing cup provided with each bottle), 4 times daily, performing vigorous mouthwashes for 1 minute and then spitting out all the solution after use. Swallowing the mouthwash is not recommended.

Copaíba

Placebo DRUG

Placebo will be used, formulated as: liquid mint aroma 5%, Nipagin 0.1%, and distilled water q.s.p. 60 mL, packaged in a container identical to the investigational product to maintain physical characteristics and blinding. The product will be stored at room temperature and kept in the INCA pharmacy. Patients will receive the solution once a week. They will be instructed to shake the bottle before use to homogenize the solution. They should use 10 mL per mouthwash (measured with the 10 mL dosing cup provided), 4 times daily, performing vigorous mouthwashes for 1 minute and then spitting out all the solution after use. Patients will be instructed not to swallow the mouthwash.

Placebo

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged 12 years or older;
• Patients indicated for autologous HSCT;
• Patients with intact oral mucosa on the first day of conditioning;
• Patients able to understand and adhere to the protocol;
• Patients able to perform the oral hygiene protocol;
• Patients who, after receiving information and instructions, can provide free and informed consent (ICF) and assent forms.

You may not qualify if:

• Patients currently receiving drugs for treatment and/or prevention of oral mucositis (OM);
• Patients who had HSCT indicated but whose procedure was canceled for any reason;
• Patients undergoing a second autologous HSCT;
• Patients reporting any allergy to copaiba-based compounds.

Sponsors & Collaborators

• Instituto Nacional de Cancer, Brazil: lead

Study Sites (1)

Instituto Nacional de Cancer, Brazil

Rio de Janeiro, Rio de Janeiro, Brazil

RECRUITING

Related Publications (67)

• Zadik Y, Arany PR, Fregnani ER, Bossi P, Antunes HS, Bensadoun RJ, Gueiros LA, Majorana A, Nair RG, Ranna V, Tissing WJE, Vaddi A, Lubart R, Migliorati CA, Lalla RV, Cheng KKF, Elad S; Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). Systematic review of photobiomodulation for the management of oral mucositis in cancer patients and clinical practice guidelines. Support Care Cancer. 2019 Oct;27(10):3969-3983. doi: 10.1007/s00520-019-04890-2. Epub 2019 Jul 8.

  PMID: 31286228 BACKGROUND

• Yarom N, Hovan A, Bossi P, Ariyawardana A, Jensen SB, Gobbo M, Saca-Hazboun H, Kandwal A, Majorana A, Ottaviani G, Pentenero M, Nasr NM, Rouleau T, Lucas AS, Treister NS, Zur E, Ranna V, Vaddi A, Barasch A, Lalla RV, Cheng KKF, Elad S; Mucositis Study Group of the Multinational Association of Supportive Care in Cancer / International Society of Oral Oncology (MASCC/ISOO). Systematic review of natural and miscellaneous agents, for the management of oral mucositis in cancer patients and clinical practice guidelines - part 2: honey, herbal compounds, saliva stimulants, probiotics, and miscellaneous agents. Support Care Cancer. 2020 May;28(5):2457-2472. doi: 10.1007/s00520-019-05256-4. Epub 2020 Feb 13.

  PMID: 32056010 BACKGROUND

• Yarom N, Ariyawardana A, Hovan A, Barasch A, Jarvis V, Jensen SB, Zadik Y, Elad S, Bowen J, Lalla RV; Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). Systematic review of natural agents for the management of oral mucositis in cancer patients. Support Care Cancer. 2013 Nov;21(11):3209-21. doi: 10.1007/s00520-013-1869-5. Epub 2013 Jun 14.

  PMID: 23764678 BACKGROUND

• WHO. WHO handbook for reporting results of cancer treatment. International Journal of Radiation Biology, 1979.

  BACKGROUND

• Wardill HR, Sonis ST, Blijlevens NMA, Van Sebille YZA, Ciorba MA, Loeffen EAH, Cheng KKF, Bossi P, Porcello L, Castillo DA, Elad S, Bowen JM; Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). Prediction of mucositis risk secondary to cancer therapy: a systematic review of current evidence and call to action. Support Care Cancer. 2020 Nov;28(11):5059-5073. doi: 10.1007/s00520-020-05579-7. Epub 2020 Jun 26.

  PMID: 32592033 BACKGROUND

• Wagner VP, Webber LP, Ortiz L, Rados PV, Meurer L, Lameira OA, Lima RR, Martins MD. Effects of Copaiba Oil Topical Administration on Oral Wound Healing. Phytother Res. 2017 Aug;31(8):1283-1288. doi: 10.1002/ptr.5845. Epub 2017 Jun 21.

  PMID: 28635033 BACKGROUND

• Valadas LAR, Gurgel MF, Mororo JM, Fonseca SGDC, Fonteles CSR, de Carvalho CBM, Fechine FV, Rodrigues Neto EM, de Franca Fonteles MM, Chagas FO, Lobo PLD, Bandeira MAM. Dose-response evaluation of a copaiba-containing varnish against streptococcus mutans in vivo. Saudi Pharm J. 2019 Mar;27(3):363-367. doi: 10.1016/j.jsps.2018.12.004. Epub 2018 Dec 15.

  PMID: 30976179 BACKGROUND

• Tobouti PL, de Andrade Martins TC, Pereira TJ, Mussi MCM. Antimicrobial activity of copaiba oil: A review and a call for further research. Biomed Pharmacother. 2017 Oct;94:93-99. doi: 10.1016/j.biopha.2017.07.092. Epub 2017 Jul 27.

  PMID: 28756369 BACKGROUND

• Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4.

  PMID: 33538338 BACKGROUND

• Sonis ST. Mucositis: The impact, biology and therapeutic opportunities of oral mucositis. Oral Oncol. 2009 Dec;45(12):1015-20. doi: 10.1016/j.oraloncology.2009.08.006. Epub 2009 Oct 13.

  PMID: 19828360 BACKGROUND

• Sonis ST, Elting LS, Keefe D, Peterson DE, Schubert M, Hauer-Jensen M, Bekele BN, Raber-Durlacher J, Donnelly JP, Rubenstein EB; Mucositis Study Section of the Multinational Association for Supportive Care in Cancer; International Society for Oral Oncology. Perspectives on cancer therapy-induced mucosal injury: pathogenesis, measurement, epidemiology, and consequences for patients. Cancer. 2004 May 1;100(9 Suppl):1995-2025. doi: 10.1002/cncr.20162.

  PMID: 15108222 BACKGROUND

• SONIS, S. T. The pathobiology of mucositis. Nature Reviews CancerNature Publishing Group, , 2004. . Acesso em: 1 fev. 2020

  BACKGROUND

• Sonis ST, Eilers JP, Epstein JB, LeVeque FG, Liggett WH Jr, Mulagha MT, Peterson DE, Rose AH, Schubert MM, Spijkervet FK, Wittes JP. Validation of a new scoring system for the assessment of clinical trial research of oral mucositis induced by radiation or chemotherapy. Mucositis Study Group. Cancer. 1999 May 15;85(10):2103-13. doi: 10.1002/(sici)1097-0142(19990515)85:103.0.co;2-0.

  PMID: 10326686 BACKGROUND

• Simoes CA, Conde NC, Venancio GN, Milerio PS, Bandeira MF, da Veiga Junior VF. Antibacterial Activity of Copaiba Oil Gel on Dental Biofilm. Open Dent J. 2016 May 11;10:188-95. doi: 10.2174/1874210601610010188. eCollection 2016.

  PMID: 27386004 BACKGROUND

• Silva LC, Sacono NT, Freire Mdo C, Costa LR, Batista AC, Silva GB. The Impact of Low-Level Laser Therapy on Oral Mucositis and Quality of Life in Patients Undergoing Hematopoietic Stem Cell Transplantation Using the Oral Health Impact Profile and the Functional Assessment of Cancer Therapy-Bone Marrow Transplantation Questionnaires. Photomed Laser Surg. 2015 Jul;33(7):357-63. doi: 10.1089/pho.2015.3911.

  PMID: 26154723 BACKGROUND

• Silva GB, Mendonca EF, Bariani C, Antunes HS, Silva MA. The prevention of induced oral mucositis with low-level laser therapy in bone marrow transplantation patients: a randomized clinical trial. Photomed Laser Surg. 2011 Jan;29(1):27-31. doi: 10.1089/pho.2009.2699. Epub 2010 Oct 22.

  PMID: 20969443 BACKGROUND

• 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.

  PMID: 14724910 BACKGROUND

• Schubert MM, Eduardo FP, Guthrie KA, Franquin JC, Bensadoun RJ, Migliorati CA, Lloid CM, Eduardo CP, Walter NF, Marques MM, Hamdi M. A phase III randomized double-blind placebo-controlled clinical trial to determine the efficacy of low level laser therapy for the prevention of oral mucositis in patients undergoing hematopoietic cell transplantation. Support Care Cancer. 2007 Oct;15(10):1145-54. doi: 10.1007/s00520-007-0238-7. Epub 2007 Mar 29.

  PMID: 17393191 BACKGROUND

• Salvador DRN, Soave DF, Sacono NT, de Castro EF, Silva GBL, E Silva LP, Silva TA, Valadares MC, Mendonca EF, Batista AC. Effect of photobiomodulation therapy on reducing the chemo-induced oral mucositis severity and on salivary levels of CXCL8/interleukin 8, nitrite, and myeloperoxidase in patients undergoing hematopoietic stem cell transplantation: a randomized clinical trial. Lasers Med Sci. 2017 Nov;32(8):1801-1810. doi: 10.1007/s10103-017-2263-1. Epub 2017 Jun 29.

  PMID: 28664388 BACKGROUND

• Sahebjamee M, Mansourian A, Hajimirzamohammad M, Zadeh MT, Bekhradi R, Kazemian A, Manifar S, Ashnagar S, Doroudgar K. Comparative Efficacy of Aloe vera and Benzydamine Mouthwashes on Radiation-induced Oral Mucositis: A Triple-blind, Randomised, Controlled Clinical Trial. Oral Health Prev Dent. 2015;13(4):309-15. doi: 10.3290/j.ohpd.a33091.

  PMID: 25431805 BACKGROUND

• Ricardo LM, Dias BM, Mugge FLB, Leite VV, Brandao MGL. Evidence of traditionality of Brazilian medicinal plants: The case studies of Stryphnodendron adstringens (Mart.) Coville (barbatimao) barks and Copaifera spp. (copaiba) oleoresin in wound healing. J Ethnopharmacol. 2018 Jun 12;219:319-336. doi: 10.1016/j.jep.2018.02.042. Epub 2018 Mar 2.

  PMID: 29501844 BACKGROUND

• Ramos GA, Piragibe MMM, Moreira MCR, Antunes HS. Polymicrobial infection of the oral mucosa after hematopoietic stem cell transplantation. Case report. Hematol Transfus Cell Ther. 2019 Oct-Dec;41(4):360-364. doi: 10.1016/j.htct.2019.02.003. Epub 2019 May 12. No abstract available.

  PMID: 31582339 BACKGROUND

• PIERI, F. A.; MUSSI, M. C.; MOREIRA, M. A. S. Óleo de copaíba (Copaifera sp.): Histórico, extração, aplicações industrials e propriedades medicinais. Revista Brasileira de Plantas Medicinais, v. 11, n. 4, p. 465-472, 2009.

  BACKGROUND

• Pieri FA, Mussi MC, Fiorini JE, Moreira MA, Schneedorf JM. Bacteriostatic effect of copaiba oil (Copaifera officinalis) against Streptococcus mutans. Braz Dent J. 2012;23(1):36-8. doi: 10.1590/s0103-64402012000100006.

  PMID: 22460312 BACKGROUND

• Pfeifer Barbosa AL, Wenzel-Storjohann A, Barbosa JD, Zidorn C, Peifer C, Tasdemir D, Cicek SS. Antimicrobial and cytotoxic effects of the Copaifera reticulata oleoresin and its main diterpene acids. J Ethnopharmacol. 2019 Apr 6;233:94-100. doi: 10.1016/j.jep.2018.11.029. Epub 2018 Nov 23.

  PMID: 30472403 BACKGROUND

• Oton-Leite AF, Silva GB, Morais MO, Silva TA, Leles CR, Valadares MC, Pinezi JC, Batista AC, Mendonca EF. Effect of low-level laser therapy on chemoradiotherapy-induced oral mucositis and salivary inflammatory mediators in head and neck cancer patients. Lasers Surg Med. 2015 Apr;47(4):296-305. doi: 10.1002/lsm.22349. Epub 2015 Mar 30.

  PMID: 25824475 BACKGROUND

• Nishii M, Soutome S, Kawakita A, Yutori H, Iwata E, Akashi M, Hasegawa T, Kojima Y, Funahara M, Umeda M, Komori T. Factors associated with severe oral mucositis and candidiasis in patients undergoing radiotherapy for oral and oropharyngeal carcinomas: a retrospective multicenter study of 326 patients. Support Care Cancer. 2020 Mar;28(3):1069-1075. doi: 10.1007/s00520-019-04885-z. Epub 2019 Jun 8.

  PMID: 31177394 BACKGROUND

• NIH, U. S. D. O. H. A. H. S. Common Terminology Criteria for Adverse Events - Version 5.0. Definitions, 2017.

  BACKGROUND

• NEVILLE, B. W. et al. Patologia oral e maxilofacial. Quarta edição ed. Rio de Janeiro: Saunders Elsevier, 2016.

  BACKGROUND

• Migliorati C, Hewson I, Lalla RV, Antunes HS, Estilo CL, Hodgson B, Lopes NN, Schubert MM, Bowen J, Elad S; Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). Systematic review of laser and other light therapy for the management of oral mucositis in cancer patients. Support Care Cancer. 2013 Jan;21(1):333-41. doi: 10.1007/s00520-012-1605-6. Epub 2012 Sep 22.

  PMID: 23001179 BACKGROUND

• Menezes ACDS, Alves LDB, Ramos GA, Schirmer MR, Moreira MCR, Piragibe MMM, de Melo AC, Antunes HS. The multiple presentation of oral actinomycosis in post-hematopoietic stem cell transplantation patients: case series. Hematol Transfus Cell Ther. 2024 Dec;46 Suppl 6(Suppl 6):S398-S404. doi: 10.1016/j.htct.2023.11.003. Epub 2023 Dec 20. No abstract available.

  PMID: 38182467 BACKGROUND

• Menezes ACDS, Alves LDB, Goldemberg DC, de Melo AC, Antunes HS. Anti-inflammatory and wound healing effect of Copaiba oleoresin on the oral cavity: A systematic review. Heliyon. 2022 Feb 19;8(2):e08993. doi: 10.1016/j.heliyon.2022.e08993. eCollection 2022 Feb.

  PMID: 35243105 BACKGROUND

• MENEZES, A. C. et al. Abordagem clínica e terapêutica da mucosite oral induzida por radioterapia e quimioterapia em pacientes com câncer. Revistas, v. 71, n. 1, p. 35, 2014.

  BACKGROUND

• Mauramo M, Grolimund P, Egli A, Passweg J, Halter J, Waltimo T. Dissociations of oral foci of infections with infectious complications and survival after haematopoietic stem cell transplantation. PLoS One. 2019 Dec 18;14(12):e0225099. doi: 10.1371/journal.pone.0225099. eCollection 2019.

  PMID: 31851665 BACKGROUND

• Martins AFL, Morais MO, Sousa-Neto SS, Oton-Leite AF, Pereira CH, Valadares MC, Freitas NMA, Batista AC, Leles CR, Mendonca EF. The Effect of Photobiomodulation on Nitrite and Inflammatory Activity in Radiotherapy-Induced Oral Mucositis: A Randomized Clinical Trial. Lasers Surg Med. 2021 Jul;53(5):671-683. doi: 10.1002/lsm.23328. Epub 2020 Sep 30.

  PMID: 32997817 BACKGROUND

• Mackall C, Fry T, Gress R, Peggs K, Storek J, Toubert A; Center for International Blood and Marrow Transplant Research (CIBMTR); National Marrow Donor Program (NMDP); European Blood and Marrow Transplant Group (EBMT); American Society of Blood and Marrow Transplantation (ASBMT); Canadian Blood and Marrow Transplant Group (CBMTG); Infectious Disease Society of America (IDSA); Society for Healthcare Epidemiology of America (SHEA); Association of Medical Microbiology and Infectious Diseases Canada (AMMI); Centers for Disease Control and Prevention (CDC). Background to hematopoietic cell transplantation, including post transplant immune recovery. Bone Marrow Transplant. 2009 Oct;44(8):457-62. doi: 10.1038/bmt.2009.255. No abstract available.

  PMID: 19861978 BACKGROUND

• Logan RM, Al-Azri AR, Bossi P, Stringer AM, Joy JK, Soga Y, Ranna V, Vaddi A, Raber-Durlacher JE, Lalla RV, Cheng KKF, Elad S; Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). Systematic review of growth factors and cytokines for the management of oral mucositis in cancer patients and clinical practice guidelines. Support Care Cancer. 2020 May;28(5):2485-2498. doi: 10.1007/s00520-019-05170-9. Epub 2020 Feb 21.

  PMID: 32080767 BACKGROUND

• Lima CS, de Medeiros BJ, Favacho HA, dos Santos KC, de Oliveira BR, Taglialegna JC, da Costa EV, de Campos KJ, Carvalho JC. Pre-clinical validation of a vaginal cream containing copaiba oil (reproductive toxicology study). Phytomedicine. 2011 Sep 15;18(12):1013-23. doi: 10.1016/j.phymed.2011.05.004. Epub 2011 Jun 12.

  PMID: 21665449 BACKGROUND

• Leandro LM, Vargas Fde S, Barbosa PC, Neves JK, da Silva JA, da Veiga-Junior VF. Chemistry and biological activities of terpenoids from copaiba (Copaifera spp.) oleoresins. Molecules. 2012 Mar 30;17(4):3866-89. doi: 10.3390/molecules17043866.

  PMID: 22466849 BACKGROUND

• Lalla RV, Bowen J, Barasch A, Elting L, Epstein J, Keefe DM, McGuire DB, Migliorati C, Nicolatou-Galitis O, Peterson DE, Raber-Durlacher JE, Sonis ST, Elad S; Mucositis Guidelines Leadership Group of the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO). MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer. 2014 May 15;120(10):1453-61. doi: 10.1002/cncr.28592. Epub 2014 Feb 25.

  PMID: 24615748 BACKGROUND

• Kiyomi A, Yoshida K, Arai C, Usuki R, Yamazaki K, Hoshino N, Kurokawa A, Imai S, Suzuki N, Toyama A, Sugiura M. Salivary inflammatory mediators as biomarkers for oral mucositis and oral mucosal dryness in cancer patients: A pilot study. PLoS One. 2022 Apr 27;17(4):e0267092. doi: 10.1371/journal.pone.0267092. eCollection 2022.

  PMID: 35476641 BACKGROUND

• Khouri VY, Stracieri AB, Rodrigues MC, Moraes DA, Pieroni F, Simoes BP, Voltarelli JC. Use of therapeutic laser for prevention and treatment of oral mucositis. Braz Dent J. 2009;20(3):215-20. doi: 10.1590/s0103-64402009000300008.

  PMID: 19784467 BACKGROUND

• Jones JA, Avritscher EB, Cooksley CD, Michelet M, Bekele BN, Elting LS. Epidemiology of treatment-associated mucosal injury after treatment with newer regimens for lymphoma, breast, lung, or colorectal cancer. Support Care Cancer. 2006 Jun;14(6):505-15. doi: 10.1007/s00520-006-0055-4. Epub 2006 Apr 7.

  PMID: 16601950 BACKGROUND

• INCA, I. N. DE C. J. A. G. DA S. Estimativa 2023: Incidêcia de Câncer no Brasil. Disponível em: <https://www.gov.br/inca/pt-br/assuntos/cancer/numeros/estimativa/estado-capital/brasil>. Acesso em: 24 nov. 2022.

  BACKGROUND

• INCA, I. N. DE C. Cuidados paliativos oncológicos. [s.l: s.n.].

  BACKGROUND

• Hong CHL, Gueiros LA, Fulton JS, Cheng KKF, Kandwal A, Galiti D, Fall-Dickson JM, Johansen J, Ameringer S, Kataoka T, Weikel D, Eilers J, Ranna V, Vaddi A, Lalla RV, Bossi P, Elad S; Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO). Systematic review of basic oral care for the management of oral mucositis in cancer patients and clinical practice guidelines. Support Care Cancer. 2019 Oct;27(10):3949-3967. doi: 10.1007/s00520-019-04848-4. Epub 2019 Jul 8.

  PMID: 31286232 BACKGROUND

• Gomes Nde M, de Rezende CM, Fontes SP, Matheus ME, Pinto Ada C, Fernandes PD. Characterization of the antinociceptive and anti-inflammatory activities of fractions obtained from Copaifera multijuga Hayne. J Ethnopharmacol. 2010 Mar 2;128(1):177-83. doi: 10.1016/j.jep.2010.01.005. Epub 2010 Jan 12.

  PMID: 20064592 BACKGROUND

• Gelmini F, Beretta G, Anselmi C, Centini M, Magni P, Ruscica M, Cavalchini A, Maffei Facino R. GC-MS profiling of the phytochemical constituents of the oleoresin from Copaifera langsdorffii Desf. and a preliminary in vivo evaluation of its antipsoriatic effect. Int J Pharm. 2013 Jan 20;440(2):170-8. doi: 10.1016/j.ijpharm.2012.08.021. Epub 2012 Aug 20.

  PMID: 22939967 BACKGROUND

• Ferreira B, da Motta Silveira FM, de Orange FA. Low-level laser therapy prevents severe oral mucositis in patients submitted to hematopoietic stem cell transplantation: a randomized clinical trial. Support Care Cancer. 2016 Mar;24(3):1035-42. doi: 10.1007/s00520-015-2881-8. Epub 2015 Aug 7.

  PMID: 26248655 BACKGROUND

• Estevao LR, Medeiros JP, Baratella-Evencio L, Simoes RS, Mendonca Fde S, Evencio-Neto J. Effects of the topical administration of copaiba oil ointment (Copaifera langsdorffii) in skin flaps viability of rats. Acta Cir Bras. 2013 Dec;28(12):863-9. doi: 10.1590/s0102-86502013001200009.

  PMID: 24316860 BACKGROUND

• Elad S, Cheng KKF, Lalla RV, Yarom N, Hong C, Logan RM, Bowen J, Gibson R, Saunders DP, Zadik Y, Ariyawardana A, Correa ME, Ranna V, Bossi P; Mucositis Guidelines Leadership Group of the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO). MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer. 2020 Oct 1;126(19):4423-4431. doi: 10.1002/cncr.33100. Epub 2020 Jul 28.

  PMID: 32786044 BACKGROUND

• Elad S, Raber-Durlacher JE, Brennan MT, Saunders DP, Mank AP, Zadik Y, Quinn B, Epstein JB, Blijlevens NM, Waltimo T, Passweg JR, Correa ME, Dahllof G, Garming-Legert KU, Logan RM, Potting CM, Shapira MY, Soga Y, Stringer J, Stokman MA, Vokurka S, Wallhult E, Yarom N, Jensen SB. Basic oral care for hematology-oncology patients and hematopoietic stem cell transplantation recipients: a position paper from the joint task force of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) and the European Society for Blood and Marrow Transplantation (EBMT). Support Care Cancer. 2015 Jan;23(1):223-36. doi: 10.1007/s00520-014-2378-x. Epub 2014 Sep 5.

  PMID: 25189149 BACKGROUND

• Diefenbach AL, Muniz FWMG, Oballe HJR, Rosing CK. Antimicrobial activity of copaiba oil (Copaifera ssp.) on oral pathogens: Systematic review. Phytother Res. 2018 Apr;32(4):586-596. doi: 10.1002/ptr.5992. Epub 2017 Nov 29.

  PMID: 29193389 BACKGROUND

• Dias-da-Silva MA, Pereira AC, Marin MC, Salgado MA. The influence of topic and systemic administration of copaiba oil on the alveolar wound healing after tooth extraction in rats. J Clin Exp Dent. 2013 Oct 1;5(4):e169-73. doi: 10.4317/jced.51104. eCollection 2013 Oct 1.

  PMID: 24455075 BACKGROUND

• de Castro CG Jr, Gregianin LJ, Brunetto AL. [Bone marrow transplantation and cord blood transplantation in children]. J Pediatr (Rio J). 2001 Sep-Oct;77(5):345-60. doi: 10.2223/jped.275. Portuguese.

  PMID: 14647838 BACKGROUND

• Davies AN, Broadley K, Beighton D. Salivary gland hypofunction in patients with advanced cancer. Oral Oncol. 2002 Oct;38(7):680-5. doi: 10.1016/s1368-8375(01)00133-6.

  PMID: 12167420 BACKGROUND

• Dalenogare DP, Ferro PR, De Pra SDT, Rigo FK, de David Antoniazzi CT, de Almeida AS, Damiani AP, Strapazzon G, de Oliveira Sardinha TT, Galvani NC, Boligon AA, de Andrade VM, da Silva Brum E, Oliveira SM, Trevisan G. Antinociceptive activity of Copaifera officinalis Jacq. L oil and kaurenoic acid in mice. Inflammopharmacology. 2019 Aug;27(4):829-844. doi: 10.1007/s10787-019-00588-3. Epub 2019 May 16.

  PMID: 31098702 BACKGROUND

• da Trindade R, da Silva JK, Setzer WN. Copaifera of the Neotropics: A Review of the Phytochemistry and Pharmacology. Int J Mol Sci. 2018 May 18;19(5):1511. doi: 10.3390/ijms19051511.

  PMID: 29783680 BACKGROUND

• Bossi P, Bergamini C, Miceli R, Cova A, Orlandi E, Resteghini C, Locati L, Alfieri S, Imbimbo M, Granata R, Mariani L, Iacovelli NA, Huber V, Cavallo A, Licitra L, Rivoltini L. Salivary Cytokine Levels and Oral Mucositis in Head and Neck Cancer Patients Treated With Chemotherapy and Radiation Therapy. Int J Radiat Oncol Biol Phys. 2016 Dec 1;96(5):959-966. doi: 10.1016/j.ijrobp.2016.08.047. Epub 2016 Sep 6.

  PMID: 27745982 BACKGROUND

• Barrach RH, Souza MP, Silva DP, Lopez PS, Montovani JC. Oral changes in individuals undergoing hematopoietic stem cell transplantation. Braz J Otorhinolaryngol. 2015 Mar-Apr;81(2):141-7. doi: 10.1016/j.bjorl.2014.04.004. Epub 2014 Oct 22.

  PMID: 25458262 BACKGROUND

• Balassa K, Danby R, Rocha V. Haematopoietic stem cell transplants: principles and indications. Br J Hosp Med (Lond). 2019 Jan 2;80(1):33-39. doi: 10.12968/hmed.2019.80.1.33.

  PMID: 30592675 BACKGROUND

• ASSOCIAÇÃO BRASILEIRA DE TRANSPLANTE DE ÓRGÃOS. Registro Brasileiro de Transplante. Veículo Oficial da Associação Brasileira de Transplante de Órgãos, n. n°4, 2023.

  BACKGROUND

• Armitage JO. Bone marrow transplantation. N Engl J Med. 1994 Mar 24;330(12):827-38. doi: 10.1056/NEJM199403243301206. No abstract available.

  PMID: 8114836 BACKGROUND

• Ariyawardana A, Cheng KKF, Kandwal A, Tilly V, Al-Azri AR, Galiti D, Chiang K, Vaddi A, Ranna V, Nicolatou-Galitis O, Lalla RV, Bossi P, Elad S; Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO). Systematic review of anti-inflammatory agents for the management of oral mucositis in cancer patients and clinical practice guidelines. Support Care Cancer. 2019 Oct;27(10):3985-3995. doi: 10.1007/s00520-019-04888-w. Epub 2019 Jul 8.

  PMID: 31286230 BACKGROUND

• Antunes HS, Herchenhorn D, Small IA, Araujo CM, Viegas CM, Cabral E, Rampini MP, Rodrigues PC, Silva TG, Ferreira EM, Dias FL, Ferreira CG. Phase III trial of low-level laser therapy to prevent oral mucositis in head and neck cancer patients treated with concurrent chemoradiation. Radiother Oncol. 2013 Nov;109(2):297-302. doi: 10.1016/j.radonc.2013.08.010. Epub 2013 Sep 14.

  PMID: 24044799 BACKGROUND

• Antunes HS, de Azevedo AM, da Silva Bouzas LF, Adao CA, Pinheiro CT, Mayhe R, Pinheiro LH, Azevedo R, D'Aiuto de Matos V, Rodrigues PC, Small IA, Zangaro RA, Ferreira CG. Low-power laser in the prevention of induced oral mucositis in bone marrow transplantation patients: a randomized trial. Blood. 2007 Mar 1;109(5):2250-5. doi: 10.1182/blood-2006-07-035022. Epub 2006 Oct 19.

  PMID: 17053058 BACKGROUND

• Ames-Sibin AP, Barizao CL, Castro-Ghizoni CV, Silva FMS, Sa-Nakanishi AB, Bracht L, Bersani-Amado CA, Marcal-Natali MR, Bracht A, Comar JF. beta-Caryophyllene, the major constituent of copaiba oil, reduces systemic inflammation and oxidative stress in arthritic rats. J Cell Biochem. 2018 Dec;119(12):10262-10277. doi: 10.1002/jcb.27369. Epub 2018 Aug 21.

  PMID: 30132972 BACKGROUND

MeSH Terms

Conditions

Stomatitis; Ulcer

Condition Hierarchy (Ancestors)

Mouth Diseases; Stomatognathic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Héliton Spíndola, PhD

  Instituto Nacional de Cancer

  STUDY DIRECTOR

Central Study Contacts

Ana Carolina Menezes, PhD' student

CONTACT

+55 21 32041859; ana.smenezes@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Both participants and the study team will be blinded to group allocation. The pharmacy team (unblinded) will dispense the investigational product/placebo.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: Patients will be randomized into two groups (Group A: Low-level laser therapy (LLLT) + copaiba mouthwash and Group B: LLLT + placebo mouthwash). After confirming eligibility (all inclusion/exclusion criteria met) and signing the ICF/assent, participants will be randomized 1:1 to the study groups using REDCap® software by an unblinded pharmacist trained for this task. Both participants and the study team will be blinded to group allocation. The pharmacy team (unblinded) will dispense the investigational product/placebo. Daily participant follow-up (outcome assessment) will begin on the first day of conditioning and continue until engraftment (third consecutive day with neutrophil count ≥ 500 cells/mm³) and/or OM healing. On the first day, participants will receive the initial supply of the investigational product/placebo and be instructed to start its use.

Study Record Dates

• First Submitted: January 7, 2026
• First Posted: September 9, 2026
• Study Start: March 29, 2026
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): February 1, 2028
• Last Updated: September 9, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)