Manuka Honey in Preventing Esophagitis-Related Pain in Patients Receiving Chemotherapy and Radiation Therapy For Lung Cancer

Pain Clinical Trial

Official title:

Phase II Randomized Trial of Prophylactic Manuka Honey for the Reduction of Chemoradiation Therapy Induced Esophagitis-Related Pain During the Treatment of Lung Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01262560
• Other study ID #: RTOG 1012
• Secondary ID: RTOG-1012CDR0000
• Status: Completed
• Phase: Phase 2
• First received: December 16, 2010
• Last updated: August 29, 2017
• Start date: February 2012
• Est. completion date: November 2014

Study information

• Verified date: August 2017
• Source: Radiation Therapy Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Manuka honey may prevent or reduce esophagitis-related pain caused by chemotherapy and radiation therapy. It is not yet known whether Manuka honey is more effective than standard care in preventing pain.

PURPOSE: This randomized phase II clinical trial is studying Manuka honey to see how well it works in preventing esophagitis-related pain in patients receiving chemotherapy and radiation therapy for lung cancer.

Description:

OBJECTIVES:

Primary

• Evaluate the relative efficacy of 4 times a day consumption of liquid or lozenge Manuka honey to delay or prevent radiation esophagitis-related pain (during combined chemotherapy and radiation therapy for lung cancer) as compared to standard supportive treatment, as measured at week 4 by Numerical Rating Pain Scale (NRPS) for pain upon swallowing.

Secondary

• Evaluate the trend of severity of radiation esophagitis-related pain during combined chemotherapy and radiation therapy for lung cancer using weekly measurements of the NRPS.

• Evaluate the adverse events associated with Manuka honey, as measured by CTCAE, v. 4.

• Evaluate the severity of radiation esophagitis (grade 3-4, CTCAE, v. 4).

• Assess weight loss (percent weight change from baseline to 4 weeks).

• Assess quality of life (QOL) and pain, as measured by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-30) global QOL score and pain symptom subscale.

• Assess patient-reported dysphagia via a daily patient log.

• Assess nutritional status, as measured by the mean change in serum prealbumin levels from baseline to 4 weeks.

• Assess opioid use by collecting the patient's narcotic use in the previous 24-hour period at each weekly evaluation.

• Evaluate patient-reported adverse events associated with Manuka honey using the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).

OUTLINE: This is a multicenter study. Patients are stratified according to the percentage of esophagus in the radiation field (V60 < 30% vs V60 ≥ 30%). Patients are randomized to 1 of 3 treatment arms.

• Arm I: Patients receive standard supportive care for esophagitis-related pain as needed during chemoradiotherapy.

• Arm II: Patients swallow liquid Manuka honey slowly over 3-5 minutes. Patients must refrain from eating and drinking for 1 hour after administration. Treatment continues 4 times per day during chemoradiotherapy.

• Arm III: Patients place Manuka honey lozenges in their mouth one at a time and swallow the honey as it dissolves (no chewing or swallowing it whole). Patients must refrain from eating and drinking for 1 hour after administration. Treatment continues 4 times per day during chemoradiotherapy.

Patients complete quality of life, pain swallowing diary, and pain assessments (Numerical Rating Pain Scale, EORTC QLQ-30 and Pain Subscale, and PRO-CTCAE) periodically during study treatment.

Patients are followed up at 12 weeks from the start of study treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 163
• Est. completion date: November 2014
• Est. primary completion date: February 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Patients being treated with combination chemotherapy (definitive or adjuvant) and radiation therapy once daily for small cell or non-small cell lung cancer (primary population for the trial)

• Patients can receive chemoradiotherapy while on a Radiation Therapy Oncology Group (RTOG) lung trial or while not being on a clinical trial

• No patients receiving chemoradiotherapy while enrolled on a single institution trial or trials coordinated by other cooperative groups

• No patients with metastatic disease

• At least 5 cm of the esophagus must be in the 60 Gy isodose volume in 1.6 to 2.0 Gy fractions

PATIENT CHARACTERISTICS:

• Age 18 and up

• Able to swallow thick liquids prior to treatment

• Able to speak English or Spanish in order to complete required forms (verbal completion is adequate)

• No patients with poorly controlled diabetes

• No known hypersensitivity to honey

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• No patients who have received prior chemotherapy or radiation therapy

• No patients receiving more than once daily treatments

• Therapeutic use of honey other than the Manuka honey provided for this trial is not allowed while patients are on study

• Patients must also avoid honey-flavored medical products and/or sugary, viscous substances

• Amifostine is not permitted

Related Conditions & MeSH terms

• Deglutition Disorders
• Dysphagia
• Esophagitis
• Lung Cancer
• Lung Neoplasms
• Pain

Intervention

Drug:
• Manuka honey in liquid form
Patients swallow 10 cc (approximately 2 level teaspoons) of liquid Manuka honey 4 times per day while awake over an approximately 12 hour period (e.g. 8 a.m., Noon, 4 p.m., and 8 p.m.) 7 days/week during concurrent chemotherapy and radiation treatment.
• Manuka honey in lozenge form
Patients place 2 lozenges (the equivalent of 10 cc of liquid Manuka honey), one at a time, in the mouth, allowing each lozenge to dissolve on the tongue/in the mouth, swallowing the honey as it dissolves. Patients do this 4 times per day while awake over an approximately 12 hour period (e.g. 8 a.m., Noon, 4 p.m., and 8 p.m.) 7 days/week during concurrent chemotherapy and radiation treatment.
• Standard supportive care
Patients receive standard supporting care for esophagitis-related pain as needed during concurrent chemotherapy and radiation treatment. The following regimen is recommended, but the local standard of care is permitted. A compound containing viscous lidocaine and magnesium aluminum oxide (Maalox®); Liquid or solid oxycodone, 5-10 mg, every 3 hours as needed.

Locations

Country	Name	City	State
United States	Rosenfeld Cancer Center at Abington Memorial Hospital	Abington	Pennsylvania
United States	St. Joseph Cancer Center	Bellingham	Washington
United States	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania
United States	Mercy Cancer Center at Mercy Medical Center	Canton	Ohio
United States	Presbyterian Cancer Center at Presbyterian Hospital	Charlotte	North Carolina
United States	Case Comprehensive Cancer Center	Cleveland	Ohio
United States	Cleveland Clinic Cancer Center at Fairview Hospital	Cleveland	Ohio
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	Payson Center for Cancer Care at Concord Hospital	Concord	New Hampshire
United States	Geisinger Cancer Institute at Geisinger Health	Danville	Pennsylvania
United States	Seacoast Cancer Center at Wentworth - Douglass Hospital	Dover	New Hampshire
United States	Northeast Radiation Oncology Center	Dunmore	Pennsylvania
United States	Duke Cancer Institute	Durham	North Carolina
United States	CCOP - Hematology-Oncology Associates of Central New York	East Syracuse	New York
United States	Piedmont Fayette Hospital	Fayetteville	Georgia
United States	Parkview Regional Cancer Center at Parkview Health	Fort Wayne	Indiana
United States	University of Texas Medical Branch	Galveston	Texas
United States	Adams Cancer Center	Gettysburg	Pennsylvania
United States	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin
United States	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	Cherry Tree Cancer Center	Hanover	Pennsylvania
United States	Pardee Memorial Hospital	Hendersonville	North Carolina
United States	Hawaii Medical Center - East	Honolulu	Hawaii
United States	Queen's Cancer Institute at Queen's Medical Center	Honolulu	Hawaii
United States	Cape Cod Hospital	Hyannis	Massachusetts
United States	Cleveland Clinic Cancer Center	Independence	Ohio
United States	Baptist Cancer Institute - Jacksonville	Jacksonville	Florida
United States	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	Lucille P. Markey Cancer Center at University of Kentucky	Lexington	Kentucky
United States	Monmouth Medical Center	Long Branch	New Jersey
United States	Elliot Regional Cancer Center at Elliot Hospital	Manchester	New Hampshire
United States	Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton	Marlton	New Jersey
United States	Hillcrest Cancer Center at Hillcrest Hospital	Mayfield Heights	Ohio
United States	CCOP - Mount Sinai Medical Center	Miami Beach	Florida
United States	Trinity CancerCare Center	Minot	North Dakota
United States	Providence Cancer Center at Providence Hospital	Mobile	Alabama
United States	Cancer Center at Ball Memorial Hospital	Muncie	Indiana
United States	CCOP - Christiana Care Health Services	Newark	Delaware
United States	Florida Cancer Center - Palatka	Palatka	Florida
United States	Cancer Center of Paoli Memorial Hospital	Paoli	Pennsylvania
United States	Parma Community General Hospital	Parma	Ohio
United States	Regional Cancer Center at Singing River Hospital	Pascagoula	Mississippi
United States	OSF St. Francis Medical Center	Peoria	Illinois
United States	FirstHealth Moore Regional Community Hospital Comprehensive Cancer Center	Pinehurst	North Carolina
United States	Rex Cancer Center at Rex Hospital	Raleigh	North Carolina
United States	Highland Hospital of Rochester	Rochester	New York
United States	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York
United States	CentraCare Clinic - River Campus	Saint Cloud	Minnesota
United States	David C. Pratt Cancer Center at St. John's Mercy	Saint Louis	Missouri
United States	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis	Saint Louis	Missouri
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California
United States	Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler	Savannah	Georgia
United States	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina
United States	Stanford Cancer Center	Stanford	California
United States	CCOP - Carle Cancer Center	Urbana	Illinois
United States	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina
United States	Lankenau Cancer Center at Lankenau Hospital	Wynnewood	Pennsylvania
United States	York Cancer Center at Apple Hill Medical Center	York	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
Radiation Therapy Oncology Group	National Cancer Institute (NCI), NRG Oncology

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Radiation Esophagitis-related Pain at 4 Weeks as Measured by the Numerical Rating Pain Scale for Pain on Swallowing (NRPS)	Esophagitis-related pain was measured using patient-reported pain on swallowing as assessed by the Numerical Rating Pain Scale (NRPS), an 11-point scale (0-10) in which 0 indicates no pain and 10 indicates the worst pain imaginable. Generally, scores of 1-4 indicate mild pain, scores of 5-6 indicate moderate pain, and scores of 7-10 indicate severe pain. Change was calculated by subtracting the baseline value from the 4-week value. The experimental arms (honey) were compared to the standard arm (supportive care).	Baseline and 4 weeks from the start of treatment
Secondary	Radiation Esophagitis-related Pain During Treatment as Measured During Treatment and 12 Weeks by the Numerical Rating Pain Scale (NRPS)	Esophagitis-related pain was measured using patient-reported pain on swallowing as assessed by the Numerical Rating Pain Scale (NRPS), an 11-point scale (0-10) in which 0 indicates no pain and 10 indicates the worst pain imaginable. Generally, scores of 1-4 indicate mild pain, scores of 5-6 indicate moderate pain, and scores of 7-10 indicate severe pain. Change was calculated by subtracting the baseline value from values at the later time points. The experimental arms (honey) were compared to the standard arm (supportive care).	Baseline, weekly during treatment, and 12 weeks from the start of treatment
Secondary	Dysphagia Via Daily Patient Log	Dysphagia, as reported by the patient, was measured by the patient swallowing diary. Swallowing score has increasing severity 1-5, where 1 = "none" and 5 = "cannot swallow liquids".	Weekly during treatment and 12 weeks from the start of treatment
Secondary	Quality of Life and Pain, as Measured by the EORTC QLQ-30 Global QOL Score and Pain Symptom Subscale at 4 and 12 Weeks	The pain symptom subscale (2 items) evaluated pain and the global score (30 items) evaluated quality of life. Each ranges from 0-100 with lower scores indicating lesser burden and improved symptoms or quality of life.	Baseline, 4 and 12 weeks from the start of treatment
Secondary	Percentage of Participants With Radiation Esophagitis Grade 3-4 (CTCAE v. 4)	Adverse events are graded using CTCAE v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE. For esophagitis specifically, Grade 3 criteria includes severely altered eating/swallowing, tube feeding, total parenteral nutrition (TPN) or hospitalization indicated. Grade 4 criteria include life-threatening consequences, urgent operative intervention indicated.	Up to 12 weeks from the start of treatment
Secondary	Percent Change in Weight From Baseline to 4 Weeks		Baseline and 4 weeks from the start of treatment
Secondary	Nutritional Status (Change in Serum Prealbumin Levels From Baseline to 4 Weeks)		Baseline and 4 weeks from the start of treatment
Secondary	Percentage of Patients Using Opioids	The percentage of patients using opioid analgesics is reported. Use of opioid analgesics was assessed for a 24-hour period before completing the assessment. Patients with at least one reported administration of opioid analgesic were considered to have received opioid analgesics.	Baseline, 4 weeks, end of radiation treatment, and 12 weeks from the start of treatment
Secondary	Adverse Events Associated With Manuka Honey Using CTCAE v4.0	Adverse events are graded using CTCAE v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.	Until 12 weeks from the start of treatment
Secondary	Patient Reported Difficulty in Swallowing Associated With Manuka Honey Using the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)	Change from baseline to four weeks in patient-reported difficulty in swallowing via the PRO-CTCAE. PRO-CTCAE is an item bank consisting of individual items to assess adverse symptom events from the patient perspective. There are 78 symptoms included in the survey but the primary item of interest assesses difficulty swallowing. For each AE in the PRO-CTCAE, between 1 and 3 items are included to assess the frequency, severity, and/or interference with activities related to that AE. Frequency questions have responses ranging from never, which is scored as a 0, to almost constantly, which is scored as a 4. Severity questions have responses ranging from none, which is scored as a 0, to very severe, which is scored as a 4. Interference questions have responses ranging from not at all, which is scored as a 0, to very much, which is scored as a 4. Difficulty in swallowing only has a severity question.	Baseline and 4 weeks from the start of treatment