The Effect of Hyperbaric OxygeN Therapy on brEast Cancer Patients With Late Radiation toxicitY - UMBRELLA HONEY Trial (HONEY)

March 28, 2025 updated by: Helena M Verkooijen, UMC Utrecht

The Effect of Hyperbaric Oxygen Therapy on Breast Cancer Patients With Late Radiation Toxicity

The "Hyperbaric OxygeN therapy on brEast cancer patients with late radiation toxicity" (HONEY) trial aims to evaluate the effectiveness of HBOT on late radiation toxicity in breast cancer patients using the trial within cohorts (TwiCs) design.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Objective: The aim of this study is to assess whether HBOT reduces pain, and improves physical functioning and QoL in breast cancer patients with late radiation toxicity.

Study design: Randomized controlled trial, nested within the prospective UMBRELLA breast cancer cohort according to the TWiC's design. UMBRELLA is a prospective cohort study including all breast cancer patients visiting the University Medical Center (UMC) Utrecht department of Radiotherapy. In total 120 patients will be randomized in a ratio of 2:1.

Study population: Breast cancer patients participating in the UMBRELLA cohort who have given informed consent to be invited for future research (e.g. cmRCT's), and who have reported symptoms of late radiation toxicity.

Intervention: Eligible patients will be referred to the HBO center for a standard HBO treatment. HBOT consists of 30-40 treatment sessions (1 session per day during 5 days per week). During the hyperbaric oxygen (HBO) sessions patients breath in 100% oxygen during 4 times 20 minutes in a hyperbaric chamber.

Main study parameters/endpoints: The primary endpoint of this study is patient reported breast/chest wall pain. Secondary endpoints are: physical functioning, QoL cosmetic outcome, physician reported pain and radiation toxicity (according to CTCAE criteria version 4.03, tissue oxygenation previous to HBOT and after HBOT and side-effects of HBOT.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
189

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Netherlands
      • Utrecht, Netherlands, 3508GA
        • University Medical Center Utrecht

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Self reported pain grade 3-4 (on a scale of 1-4) as assessed by the late radiation toxicity questionnaire;
  • Participation >12 months in the UMBRELLA cohort;
  • Previous treatment with radiotherapy for breast cancer;
  • Completed surgery and (neo)adjuvant systemic therapy except adjuvant endocrine therapy, for breast cancer.

Exclusion Criteria:

  • Poor responder to questionnaires (i.e. return of ≤ 2 UMBRELLA questionnaires);
  • Previous HBOT;
  • Contra-indications for HBOT (e.g. (severe) chronic obstructive pulmonary disease (COPD) or asthma, pacemaker, morbid obesity, epilepsy in medical history, severe heart failure);
  • Current metastatic disease or recurrent breast cancer.

Additional exclusions criteria based on screening visit:

  • Inability to follow schedule of all consecutive HBO treatments (e.g. due to scheduled holidays > 2 days);
  • Not meeting criteria for HBOT (e.g. due to complaints similar to late radiation toxicity, not caused by radiotherapy).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Hyperbaric oxygen therapy
Hyperbaric oxygen therapy consists of 30-40 treatment sessions (1 session per day during 5 days per week). During the hyperbaric oxygen (HBO) sessions the pressure will be raised to 2.4 atmospheres absolute in a hyperbaric chamber and patients breath in 100% oxygen during 4 times 20 minutes.
Drug: Hyperbaric oxygen therapy
Hyperbaric oxygen therapy in a multiperson hyperbaric oxygen chamber. Standard hyperbaric oxygen therapy provided as reimbursed by insurers.
Other Names:
  • Oxygen
No Intervention: Usual care
Usual care may consist of physiotherapy, analgetics, edema therapy

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in breast/chest wall pain: EORTC QLQ-BR23 questionnaire
Time Frame: Baseline and 6 months after baseline (i.e. 3 months after HBOT)
The primary endpoint of this study is the difference in proportion of patient-reported breast/chest wall pain grade 3-4 between control and intervention group. Pain is assessed by means of the EORTC QLQ-BR23 questionnaire on a 4-point Likert scale. At baseline all patients have a pain score of 3 or 4 (see inclusion criteria). The proportion of patients with 3-4 at 6 months will be compared between intervention and control group. A higher score indicates more pain.
Baseline and 6 months after baseline (i.e. 3 months after HBOT)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in patient-reported quality of life: (EORTC QLQ) C30
Time Frame: Baseline and 6 months after baseline (i.e. 3 months after HBOT)
Quality of life (QoL) measured by European Organisation of Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30. QoL will be scored on a scale of 0-100. A higher score indicates a better outcome. Change in score between baseline and 6 months will be compared between intervention and control group.
Baseline and 6 months after baseline (i.e. 3 months after HBOT)
Change in patient-reported late radiation toxicity
Time Frame: Baseline and 6 months after baseline (i.e. 3 months after HBOT)
Late radiation toxicity is assessed by means of a late radiation toxicity questionnaire (ability to move the arm, (breast) edema, fibrosis) in both control group and intervention group. Change in patient reported late radiation toxicity will be compared between intervention and control group. Late radiation toxicity will be assessed on a 4-point Likert scale. A higher score indicates worse outcomes.
Baseline and 6 months after baseline (i.e. 3 months after HBOT)
Physician-reported late radiation toxicity
Time Frame: Baseline (prior to HBOT), 3 months after baseline (i.e. after HBOT) and 6 months after baseline (i.e. 3 months after the last HBO session)
Assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 only in intervention group. CTCAE criteria are assessed on a scale of 0-3.
Baseline (prior to HBOT), 3 months after baseline (i.e. after HBOT) and 6 months after baseline (i.e. 3 months after the last HBO session)
Patient-reported cosmetic outcome
Time Frame: Baseline and 6 months after baseline (i.e. 3 months after HBOT)
Assessed by means of the breast cancer questionnaire (BREAST-Q) in both control group and intervention group. BREAST-Q scores will be assessed using the BREAST-Q scoring tables.
Baseline and 6 months after baseline (i.e. 3 months after HBOT)
Physician-reported cosmetic outcome
Time Frame: Baseline and 6 months after baseline (i.e. 3 months after HBOT)
Reported by means of medical photograph (cosmetic outcome judged by group of experts and "Breast Cancer Conservative Treatment - cosmetic results" (BCCT.core) program) and with physical examination using the Patient and Observer Scar Assessment Scale (POSAS) score v2.0. Physician reported cosmetic outcome will only be assessed in the intervention group.
Baseline and 6 months after baseline (i.e. 3 months after HBOT)
Number of participants with side effects of treatment with hyperbaric oxygen therapy
Time Frame: During hyperbaric oxygen treatment sessions and at 3 months after last HBO session
Side effects of HBOT will be monitored using the MacFie classification only in the intervention group.
During hyperbaric oxygen treatment sessions and at 3 months after last HBO session
Oxygenation of the skin
Time Frame: Baseline and prior to last hyperbaric oxygen session (i.e. 3 months after baseline).
Skin oxygenation will be measured prior to HBOT and after last treatment session using transcutaneous oxygen measurement. The contralateral breast will be used as a reference. Only assessed in the intervention group.
Baseline and prior to last hyperbaric oxygen session (i.e. 3 months after baseline).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
UMC Utrecht

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
The Netherlands Cancer Institute

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Helena M Verkooijen, MD, PhD, Imaging Division, UMC Utrecht

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 28, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 8, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 8, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 11, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 6, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 10, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 3, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 28, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • NL69081.041.19

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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