Study of Epidermal Growth Factor on Oral Mucositis Induced by Intensive Chemotherapy for Hematologic Malignancies - Full Text View

Sponsor:	Seoul National University Hospital
Collaborator:	Daewoong Pharmaceutical Co. LTD.
Information provided by:	Seoul National University Hospital
ClinicalTrials.gov Identifier:	NCT00845819

Purpose

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.

Condition	Intervention	Phase
Oral Mucositis	Drug: rhEGF + povidone iodine, chlorhexidine, & nystatin Drug: Placebo + povidone iodine, chlorhexidine, & nystatin	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Prevention
Official Title:	Randomized Phase II Study of Recombinant Human Epidermal Growth Factor (rhEGF) on Oral Mucositis Induced by Intensive Chemotherapy for Hematologic Malignancies

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Chlorhexidine Nystatin Iodine Chlorhexidine gluconate Iodide Povidone-iodine Urogastrone Hibiclens

U.S. FDA Resources

Further study details as provided by Seoul National University Hospital:

Primary Outcome Measures:

Incidence of oral mucositis of grade 2 or higher (NCI CTCAE 3.0) [ Time Frame: Assessed daily during application of study drugs ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Adverse events [ Time Frame: Assessed daily during application of study drugs ] [ Designated as safety issue: Yes ]
Day of onset and duration of oral mucositis of grade 2 or higher (NCI CTCAE 3.0) [ Time Frame: Assessed daily during application of study drugs ] [ Designated as safety issue: No ]
Incidence, day of onset, and duration of oral mucositis of grade 3 or higher (NCI CTCAE 3.0) [ Time Frame: Assessed daily during application of study drugs ] [ Designated as safety issue: No ]
Incidence, day of onset, and duration of oral mucositis of grade 2 or higher (WHO) [ Time Frame: Assessed daily during application of study drugs ] [ Designated as safety issue: No ]
Incidence, day of onset, and duration of oral mucositis of grade 3 or higher (WHO) [ Time Frame: Assessed daily during application of study drugs ] [ Designated as safety issue: No ]
Incidence, day of onset, and duration of oral mucositis of grade 4 or higher (WHO) [ Time Frame: Assessed daily during application of study drugs ] [ Designated as safety issue: No ]
OMDQ (oral mucositis daily questionnaire) score during treatment [ Time Frame: Assessed daily during application of study drugs ] [ Designated as safety issue: No ]

Estimated Enrollment:	138
Study Start Date:	February 2009
Estimated Study Completion Date:	February 2012
Estimated Primary Completion Date:	February 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: EGF rhEGF + povidone iodine, chlorhexidine, & nystatin	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. Other Names: Nepidermin Easyef(R)
Placebo Comparator: Placebo Placebo + povidone iodine, chlorhexidine, & nystatin	Drug: 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. Other Name: Placebo

Arms

Assigned Interventions

Active Comparator: EGF

rhEGF + povidone iodine, chlorhexidine, & nystatin

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.

Other Names:

Nepidermin
Easyef(R)

Placebo Comparator: Placebo

Placebo + povidone iodine, chlorhexidine, & nystatin

Drug: 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.

Other Name: Placebo

Detailed 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.

Eligibility

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00845819

Contacts

Contact: Sung-Soo Yoon, MD, PhD	+82-2-2072-3079	ssysmc@snu.ac.kr
Contact: Ji-Won Kim, MD	+82-11-9010-0427	werbinig@gmail.com

Locations

Korea, Republic of
Seoul National University Hospital	Recruiting
Seoul, Korea, Republic of, 110-744
Contact: Sung-Soo Yoon, MD, PhD +82-2-2072-3079 ssysmc@snu.ac.kr
Contact: Ji-Won Kim, MD +82-11-9010-0427 werbinig@gmail.com
Principal Investigator: Sung-Soo Yoon, MD, PhD
Sub-Investigator: Byoung Kook Kim, MD, PhD
Sub-Investigator: Seonyang Park, MD, PhD
Sub-Investigator: Jung-Mi Oh, PharmD
Sub-Investigator: Inho Kim, MD, PhD
Sub-Investigator: Ji-Won Kim, MD
Sub-Investigator: Kyung Im Kim, MS
Sub-Investigator: Hyun Jung Lee, MD

Sponsors and Collaborators

Seoul National University Hospital

Daewoong Pharmaceutical Co. LTD.

Investigators

Principal Investigator:

Sung-Soo Yoon, MD, PhD

Seoul National University Hospital

More Information

Publications:

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.

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.

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.

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.

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.

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 Apr 23; [Epub ahead of print]

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.

Responsible Party:	Sung-Soo Yoon, MD, PhD / Professor, Seoul National University Hospital
ClinicalTrials.gov Identifier:	NCT00845819 History of Changes
Other Study ID Numbers:	SNUH-Hema-1001
Study First Received:	February 16, 2009
Last Updated:	July 20, 2011
Health Authority:	Korea: Food and Drug Administration

Keywords provided by Seoul National University Hospital:

oral mucositis
intensive chemotherapy
stem cell transplantation
epidermal growth factor

Additional relevant MeSH terms:

Stomatitis
Mucositis
Hematologic Neoplasms
Mouth Diseases
Stomatognathic Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Neoplasms by Site
Neoplasms
Hematologic Diseases
Povidone
Chlorhexidine
Chlorhexidine gluconate
Iodine

Cadexomer iodine
Povidone-Iodine
Nystatin
Mitogens
Plasma Substitutes
Blood Substitutes
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Infective Agents, Local
Anti-Infective Agents
Disinfectants
Dermatologic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 24, 2012