Study of Epidermal Growth Factor on Oral Mucositis Induced by Intensive Chemotherapy for Hematologic Malignancies

Oral Mucositis Clinical Trial

— EGFOM  

Official title:

Randomized Phase II Study of Recombinant Human Epidermal Growth Factor (rhEGF) on Oral Mucositis Induced by Intensive Chemotherapy for Hematologic Malignancies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00845819
• Other study ID #: SNUH-Hema-1001
• Status: Completed
• Phase: Phase 2
• First received: February 16, 2009
• Last updated: January 20, 2015
• Start date: February 2009
• Est. completion date: October 2014

Study information

• Verified date: January 2015
• Source: Seoul National University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine efficacy and toxicity of recombinant human epidermal growth factor (rhEGF) as a preventive drug of oral mucositis during intensive chemotherapy with stem cell transplantation in patients with hematologic malignancies.

Description:

Oral mucositis is one of the most common adverse events during chemotherapy and affects quality of life of patients receiving chemotherapy in relation to the dose of drugs. However, there is only one drug (palifermin) approved by the US FDA for the prevention of oral mucositis and the other methods to prevent or treat oral mucositis are just empirical and lack evidences. The results of recent study demonstrated promising efficacy and minimal toxicity of recombinant human epidermal growth factor (rhEGF) as a preventive drug of oral mucositis in head and neck cancer patients undergoing radiotherapy (Wu HG, et al. Cancer 2009;115(16):3699-3708). This clinical trial is a double-blind randomized prospective single-institutional phase II study to evaluate efficacy and toxicity of recombinant human epidermal growth factor (rhEGF) as a preventive drug of oral mucositis during intensive chemotherapy with stem cell transplantation in patients with hematologic malignancies.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 138
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Patients with confirmed diagnosis of hematologic malignancies including acute & chronic leukemia, lymphoma, plasma cell dyscrasia, myelodysplastic syndrome, aplastic anemia, etc.

• Patients who are planned to receive high-dose chemotherapy with SCT

• ECOG performance status 0-2

• Informed consent

Exclusion Criteria:

• Patients having previous history of hypersensitivity to this drug or similar drugs

• Patients having oral ulcer or herpes or severe dental disease at the time of inclusion

• Patients received chemotherapy, radiotherapy, or surgery within 3 weeks

• Patients who had finished clinical trials which could affect the results of this trial within 4 weeks or are attending one at the time of inclusion

• Patients having another diseases which have worse prognosis than patients' hematologic malignancy

• Patients with major psychotic disorder or drug/alcohol abuser

• Women who are pregnant or breastfeeding

• Refusal at patients' will

• Inappropriate patients according to the investigators' opinion

Study Design

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

Related Conditions & MeSH terms

• Mucositis
• Oral Mucositis
• Stomatitis

Intervention

Drug:
• rhEGF + povidone iodine, chlorhexidine, & nystatin
Topical application of 50 µg/mL rhEGF solution twice daily + oral gargling with povidone iodine (1%), chlorhexidine (0.5%) & nystatin (5,000IU/mL) three times a day. Application of drugs begins with start of intensive chemotherapy and ends at the time of recovery from neutropenia (ANC>1000/µL for 3 days) or disappearance of oral mucositis. For each application of rhEGF, spray total 6 times at palate, oropharynx, both buccal mucosa, tongue, and gingiva.
• Placebo + povidone iodine, chlorhexidine, & nystatin
Topical application of placebo drug twice daily + oral gargling with povidone iodine (1%), chlorhexidine (0.5%), and nystatin (5,000IU/mL) three times a day. Application of drugs begins with start of intensive chemotherapy and ends at the time of recovery from neutropenia (ANC>1000/µL for 3 days) or disappearance of oral mucositis. For each application of placebo drug, spray total 6 times at palate, oropharynx, both buccal mucosa, tongue, and gingiva.

Locations

Country	Name	City	State
Korea, Republic of	Seoul National University Hospital	Seoul

Sponsors (2)

Lead Sponsor	Collaborator
Seoul National University Hospital	Daewoong Pharmaceutical Co. LTD.

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (7)

Brown GL, Curtsinger L 3rd, Brightwell JR, Ackerman DM, Tobin GR, Polk HC Jr, George-Nascimento C, Valenzuela P, Schultz GS. Enhancement of epidermal regeneration by biosynthetic epidermal growth factor. J Exp Med. 1986 May 1;163(5):1319-24. — View Citation

Epstein JB, Gorsky M, Guglietta A, Le N, Sonis ST. The correlation between epidermal growth factor levels in saliva and the severity of oral mucositis during oropharyngeal radiation therapy. Cancer. 2000 Dec 1;89(11):2258-65. — View Citation

Hong JP, Lee SW, Song SY, Ahn SD, Shin SS, Choi EK, Kim JH. Recombinant human epidermal growth factor treatment of radiation-induced severe oral mucositis in patients with head and neck malignancies. Eur J Cancer Care (Engl). 2009 Nov;18(6):636-41. doi: 10.1111/j.1365-2354.2008.00971.x. Epub 2009 Apr 23. — View Citation

Keefe DM, Schubert MM, Elting LS, Sonis ST, Epstein JB, Raber-Durlacher JE, Migliorati CA, McGuire DB, Hutchins RD, Peterson DE; Mucositis Study Section of the Multinational Association of Supportive Care in Cancer and the International Society for Oral Oncology. Updated clinical practice guidelines for the prevention and treatment of mucositis. Cancer. 2007 Mar 1;109(5):820-31. — View Citation

Sonis ST, Costa JW Jr, Evitts SM, Lindquist LE, Nicolson M. Effect of epidermal growth factor on ulcerative mucositis in hamsters that receive cancer chemotherapy. Oral Surg Oral Med Oral Pathol. 1992 Dec;74(6):749-55. — View Citation

Sonis ST, Oster G, Fuchs H, Bellm L, Bradford WZ, Edelsberg J, Hayden V, Eilers J, Epstein JB, LeVeque FG, Miller C, Peterson DE, Schubert MM, Spijkervet FK, Horowitz M. Oral mucositis and the clinical and economic outcomes of hematopoietic stem-cell transplantation. J Clin Oncol. 2001 Apr 15;19(8):2201-5. — View Citation

Wu HG, Song SY, Kim YS, Oh YT, Lee CG, Keum KC, Ahn YC, Lee SW. Therapeutic effect of recombinant human epidermal growth factor (RhEGF) on mucositis in patients undergoing radiotherapy, with or without chemotherapy, for head and neck cancer: a double-blind placebo-controlled prospective phase 2 multi-institutional clinical trial. Cancer. 2009 Aug 15;115(16):3699-708. doi: 10.1002/cncr.24414. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of oral mucositis of grade 2 or higher (NCI CTCAE 3.0)		Assessed daily during application of study drugs	No
Secondary	Adverse events		Assessed daily during application of study drugs	Yes
Secondary	Day of onset and duration of oral mucositis of grade 2 or higher (NCI CTCAE 3.0)		Assessed daily during application of study drugs	No
Secondary	Incidence, day of onset, and duration of oral mucositis of grade 3 or higher (NCI CTCAE 3.0)		Assessed daily during application of study drugs	No
Secondary	Incidence, day of onset, and duration of oral mucositis of grade 2 or higher (WHO)		Assessed daily during application of study drugs	No
Secondary	Incidence, day of onset, and duration of oral mucositis of grade 3 or higher (WHO)		Assessed daily during application of study drugs	No
Secondary	Incidence, day of onset, and duration of oral mucositis of grade 4 or higher (WHO)		Assessed daily during application of study drugs	No
Secondary	OMDQ (oral mucositis daily questionnaire) score during treatment		Assessed daily during application of study drugs	No