Topical Phenylephrine Solution in Preventing Oral Mucosa in Bone Marrow Transplant Patients Receiving Cyclophosphamide and Total Body Radiation Therapy

NCT02434146 | Terminated Phase 1 Results DMC

• 5 other identifiers: UW14068NCI-2015-005762015-0062A536700SMPH\PEDIATRICS\PEDIATRICS
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial studies the safety of topical phenylephrine solution and to see how well it works in preventing oral mucosa (mouth sores) in bone marrow transplant patients receiving cyclophosphamide and total body radiation therapy. Topical phenylephrine solution may prevent or lessen the severity of oral mucosa in patients receiving cyclophosphamide and total body radiation prior to undergoing a bone marrow transplant.

Conditions

Neoplasm; Oral Mucosa; Transplant-Related Disorder

Outcome Measures

Primary Outcomes (9)

• Area Under the Curve (AUC) for the Oral Mucositis Severity

  The mucositis AUC will be estimated using the trapezoid method and summarized in terms of means, standard deviation, median and range. This analysis will be performed in both the extended cohort as well as in the historical controls.

  Up to 3 months

• Duration of Grade 2 Oral Mucositis

  If the grade 2 oral mucositis has not been resolved (to a grade \< 2) by the last day of toxicity assessment, then the duration will be censored at the last date of toxicity assessment. Will be analyzed using the Kaplan-Meier method. The median duration of grade 2/grade 3 oral mucositis will be calculated and reported along with the corresponding 95% confidence interval. This analysis will be performed in both the extended cohort as well as in the historical controls.

  Date of onset of grade 2 oral mucositis to the date of the resolution of the grade 2 oral mucositis, assessed up to 3 months

• Duration of Grade 3 Oral Mucositis

  If the grade 3 oral mucositis has not been resolved (to a grade \< 3) by the last day of toxicity assessment, then the duration will be censored at the last date of toxicity assessment. Will be analyzed using the Kaplan-Meier method. The median duration of grade 2/grade 3 oral mucositis will be calculated and reported along with the corresponding 95% confidence interval. This analysis will be performed in both the extended cohort as well as in the historical controls.

  Date of onset of grade 3 oral mucositis to the date of resolution to grade < 3 oral mucositis, assessed up to 3 months

• Efficacy Response Rate for Preventing Oral Mucositis With Sufficient Accuracy

  If a patient experiences no higher than grade 2 oral mucositis, then s/he will be defined as a responder. If a patient experiences grade \>= 3 oral mucositis, s/he will be defined as a non-responder. Specifically, the efficacy response rate will be estimated with a standard error of less than 15% and the length of the 95% confidence interval will be less than 50%. The efficacy response rate will be summarized in tabular format. The Wilson score method will be used to calculate the 95% confidence interval for the efficacy response rate for the extended cohort.

  Up to 3 months

• Incidence of Adverse Events, Graded According to the Common Terminology Criteria for Adverse Events Version 4.0

  Adverse events (AEs) will be presented in the summary tables by preferred term nested within the System Organ Class. Verbatim description, preferred term, and system organ class for all AEs will be contained in the patient data listings. All AEs occurring after enrollment and throughout the study period will be recorded. Each toxicity event will be assigned an attribution: unrelated, unlikely, possibly, probably, or definitely phenylephrine treatment related.

  Up to 3 months

• Maximum Tolerated Dose (MTD), Defined as the Highest Dose Level of Phenylephrine Applied to the Oral Mucosa Where 0/3, 0/6, or 1/6 Patients Experience a Dose-limiting Toxicity

  Determine Maximum Tolerated Dose (MTD), the highest dose level of phenylephrine applied to the oral mucosa

  During the conditioning regimen (radiation and cyclophosphamide treatment), which is anticipated to last 1 week.

• Recommended Phase IIa Dose

  The dose of topical phenylephrine solution which will be recommended for a larger follow-up phase II efficacy study will be established after the dose cohort at the MTD has been expanded to a total of 12 patients.

  During the conditioning regimen (radiation and cyclophosphamide treatment), which is anticipated to last 1 week.

• Time to Onset of Grade 2 Oral Mucositis

  Will be analyzed using a parametric (one-parameter exponential) cure rate model. Will be performed in both the extended cohort as well as in the historical controls.

  Time between the first date of radiation or cyclophosphamide treatment to the date of the onset of grade 2 oral mucositis, assessed up to 3 months

• Time to Onset of Grade 3 Oral Mucositis

  Will be analyzed using a parametric (one-parameter exponential) cure rate model. Will be performed in both the extended cohort as well as in the historical controls.

  Time between the first date of radiation or cyclophosphamide treatment to the date of the onset of grade 3 oral mucositis, assessed up to 3 months

Study Arms (1)

Supportive care (topical phenylephrine solution)

EXPERIMENTAL

Patients undergoing a cyclophosphamide and total body irradiation regimen receive topical phenylephrine solution via spray to the oral mucosa 15-20 minutes prior to each cyclophosphamide infusion, 25-30 minutes after the beginning of each cyclophosphamide infusion, and 15-20 minutes prior to each radiation treatment.

Drug: Topical Phenylephrine Solution

Interventions

Topical Phenylephrine Solution DRUG

Given topically via spray

Supportive care (topical phenylephrine solution)

Eligibility Criteria

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

You may qualify if:

• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less
• Patients must have no evidence of active infections at the time of transplantation
• Patients must be human immunodeficiency virus (HIV) non-reactive
• Females of childbearing potential must not be pregnant or breastfeeding on admission for conditioning for SCT and a pregnancy test will be required for all females of child-bearing potential
• Patients must have a pre-transplant multi-organ assessment with the following outcome:
• A resting ejection fraction of 50% or greater which increases with exercise as demonstrated by resting/exercise multigated acquisition (MUGA)
• A forced expiratory volume in one second (FEV1) of 60% or greater, a diffusion capacity of 50% or greater, and a oxygen partial pressure (PO2) of 80 mm mercury (Hg) or greater on pulmonary function testing
• A serum creatinine of equal or less than 2.0mg/Dl and a creatinine clearance of 50 mL/min or greater on 24 hour urine collection
• A total bilirubin of less than 2.5 mg/dL, unless these values are due to underlying hematologic malignancy
• An aspartate aminotransferase (AST) less than 2 times the upper limit of normal, unless these values are due to underlying hematologic malignancy
• Be able to tolerate topical application of phenylephrine to the oral mucosa
• All patients must sign a written informed consent

You may not qualify if:

• Open or unhealed wounds or ulcers in the oral cavity
• Current use or use within past two weeks of an monoamine oxidase inhibitor (MAOI)
• Primary or secondary tumor in the oral cavity
• Known allergy to phenylephrine
• Uncontrolled hypertension (defined as blood pressure in adults \> 150/95)
• Patients on anti-hypertensive medications are eligible if blood pressure is controlled
• Enrollment in any other mucositis prevention study from screening up to day 45 post-stem cell transplant
• Patients who are not eligible to receive SCT with cyclophosphamide and total body irradiation (TBI) conditioning because they do not meet transplant criteria are also not eligible for this phenylephrine study
• Patients who have angina and/or congestive heart failure requiring treatment, or who have had a myocardial infarction within the past year
• Patients who have had any complication that makes the risk of death during transplantation from non-malignant causes greater than the risk of relapse
• Patients who have any active infection; if the infection is successfully treated, the patient may be reconsidered for transplantation at a later date
• Patients with diabetes who are not controlled by medical management will be ineligible
• Psychiatric illness requiring psychiatric counseling or medical intervention other than antidepressant medications may make an individual ineligible and will be considered on a case-by-case basis
• Psychosocial assessment by the bone marrow transplant team may identify individuals for whom this form of therapy may be contraindicated; these decisions will be based upon estimated adequacy of patient support systems and prediction of patient's compliance with medications, required diagnostic procedures, and/or follow-up care
• Patients who have an ECOG performance status of greater than 2

Sponsors & Collaborators

• University of Wisconsin, Madison: lead

Study Sites (1)

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792, United States

Location

Related Links

• University of Wisconsin Carbone Cancer Center

MeSH Terms

Conditions

Neoplasms

Limitations and Caveats

This study was closed prematurely due to decreased numbers of eligible subjects. The full target accrual number was not achieved, and no study conclusions could be made.

Results Point of Contact

• Title: Margo L Hoover-Regan
• Organization: University of Wisconsin Carbone Cancer Center

mhooverregan@pediatrics.wisc.edu

608-263-6200

Study Officials

• Margo L. Hoover-Regan

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 24, 2015
• First Posted: May 5, 2015
• Study Start: May 14, 2015
• Primary Completion: April 27, 2016
• Study Completion: January 25, 2017
• Last Updated: December 9, 2019
• Results First Posted: April 27, 2017

Record last verified: 2017-09

Locations

US (1)