Breast CancerPhase 3HONEYNCT04193722

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

A Phase 3 study testing Hyperbaric oxygen therapy in people with Breast Cancer and Radiation Toxicity, run by UMC Utrecht at 1 site in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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. Read more about this study

Who is it for?: Ages 18 years and older, women only
Conditions the study is for: Breast Cancer, Radiation Toxicity
What is being tested?: Hyperbaric oxygen therapy
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 189 participants
Where: 1 siteNetherlands
Study dates: 28 Aug 2019to 8 May 2023
Phase: Phase 3
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
Women only
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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).

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

University Medical Center Utrecht
Utrecht, Utrecht, 3508GA

Other trials in Netherlands

About this study

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

Read the 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.

Conditions: Breast Cancer, Radiation Toxicity
Being tested: Hyperbaric oxygen therapy
Keywords: Breast cancer, Radiotherapy, Hyperbaric oxygen therapy, Late toxicity, Trials within cohorts, Patient reported outcomes
Medical subject headings: Breast Neoplasms, Radiation Injuries

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Hyperbaric oxygen therapyDrug
Also called Oxygen
Hyperbaric oxygen therapy in a multiperson hyperbaric oxygen chamber. Standard hyperbaric oxygen therapy provided as reimbursed by insurers.

Study groups in NCT04193722
Study group	Role	What they receive
Hyperbaric oxygen therapy	Experimental	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. Receives: Drug: Hyperbaric oxygen therapy
Usual care	No intervention	Usual care may consist of physiotherapy, analgetics, edema therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in breast/chest wall pain: EORTC QLQ-BR23 questionnaire
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.
Measured: Baseline and 6 months after baseline (i.e. 3 months after HBOT)

Secondary outcomes (7)

Change in patient-reported quality of life: (EORTC QLQ) C30
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.
Measured: Baseline and 6 months after baseline (i.e. 3 months after HBOT)
Change in patient-reported late radiation toxicity
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.
Measured: Baseline and 6 months after baseline (i.e. 3 months after HBOT)
Physician-reported late radiation toxicity
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.
Measured: 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
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.
Measured: Baseline and 6 months after baseline (i.e. 3 months after HBOT)
Physician-reported cosmetic outcome
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.
Measured: Baseline and 6 months after baseline (i.e. 3 months after HBOT)
Number of participants with side effects of treatment with hyperbaric oxygen therapy
Side effects of HBOT will be monitored using the MacFie classification only in the intervention group.
Measured: During hyperbaric oxygen treatment sessions and at 3 months after last HBO session
Oxygenation of the skin
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.
Measured: Baseline and prior to last hyperbaric oxygen session (i.e. 3 months after baseline).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

28 Aug 20198 May 2023

First posted10 Dec 2019
Study start28 Aug 2019
Primary completion8 May 2023
Study completion8 May 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Breast CancerStudies of the same condition, open and under way.
More trials run by UMC UtrechtThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: Trial within cohorts design
Masking: None (open label)
Enrolment: 189 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04193722
Sponsor's protocol ID: NL69081.041.19
Acronym: HONEY
Status last verified: Mar 2025
First submitted: 11 Nov 2019
Last updated: 3 Apr 2025
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No

Publications

Mink van der Molen DR, Batenburg MCT, Maarse W, van den Bongard DHJG, Doeksen A, de Lange MY, van der Pol CC, Evers DJ, Lansdorp CA, van der Laan J, van de Ven PM, van der Leij F, Verkooijen HM. Hyperbaric Oxygen Therapy and Late Local Toxic Effects in Patients With Irradiated Breast Cancer: A Randomized Clinical Trial. JAMA Oncol. 2024 Apr 1;10(4):464-474. doi: 10.1001/jamaoncol.2023.6776.
PubMed 38329746
Batenburg MCT, van den Bongard HJGD, Kleynen CE, Maarse W, Witkamp A, Ernst M, Doeksen A, van Dalen T, Sier M, Schoenmaeckers EJP, Baas IO, Verkooijen HM. Assessing the effect of hyperbaric oxygen therapy in breast cancer patients with late radiation toxicity (HONEY trial): a trial protocol using a trial within a cohort design. Trials. 2020 Nov 27;21(1):980. doi: 10.1186/s13063-020-04869-z.
PubMed 33246494

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 3 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: The Effect of Hyperbaric Oxygen Therapy on Breast Cancer Patients With Late Radiation Toxicity
ClinicalTrials.gov ID: NCT04193722
Acronym / sponsor ID: HONEY / NL69081.041.19
Conditions: Breast Cancer, Radiation Toxicity
Keywords: Breast cancer, Radiotherapy, Hyperbaric oxygen therapy, Late toxicity, Trials within cohorts, Patient reported outcomes
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 189 participants (actual)
Lead sponsor: UMC UtrechtUniversity, hospital or other
Study start: 28 Aug 2019 (actual)
Primary completion: 8 May 2023 (actual)
Study completion: 8 May 2023 (actual)
First posted: 10 Dec 2019 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2
Model description: Trial within cohorts design

Arm	Type	Receives
Hyperbaric oxygen therapy	Experimental	Drug: Hyperbaric oxygen therapyHyperbaric 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.
Usual care	No intervention	–Usual care may consist of physiotherapy, analgetics, edema therapy

Who may qualify

Ages: 18 years and older
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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.

Key exclusion criteria (7 listed)

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.
Inability to follow schedule of all consecutive HBO treatments (e.g. due to scheduled holidays > 2 days);

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Hyperbaric oxygen therapyAlso: OxygenHyperbaric oxygen therapy in a multiperson hyperbaric oxygen chamber. Standard hyperbaric oxygen therapy provided as reimbursed by insurers.	Drug	Hyperbaric oxygen therapy

Primary outcome

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.

7 secondary outcomes

Change in patient-reported quality of life: (EORTC QLQ) C30
Time frame: 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)
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)
Patient-reported cosmetic outcome
Time frame: 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)
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
Oxygenation of the skin
Time frame: Baseline and prior to last hyperbaric oxygen session (i.e. 3 months after baseline).

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 3 Apr 2025.
Derived from this study: PubMed 38329746Mink van der Molen DR, Batenburg MCT, Maarse W, van den Bongard DHJG, Doeksen A, de Lange MY, van der Pol CC, Evers DJ, Lansdorp CA, van der Laan J, van de Ven PM, van der Leij F, Verkooijen HM. Hyperbaric Oxygen Therapy and Late Local Toxic Effects in Patients With Irradiated Breast Cancer: A Randomized Clinical Trial. JAMA Oncol. 2024 Apr 1;10(4):464-474. doi: 10.1001/jamaoncol.2023.6776.
Derived from this study: PubMed 33246494Batenburg MCT, van den Bongard HJGD, Kleynen CE, Maarse W, Witkamp A, Ernst M, Doeksen A, van Dalen T, Sier M, Schoenmaeckers EJP, Baas IO, Verkooijen HM. Assessing the effect of hyperbaric oxygen therapy in breast cancer patients with late radiation toxicity (HONEY trial): a trial protocol using a trial within a cohort design. Trials. 2020 Nov 27;21(1):980. doi: 10.1186/s13063-020-04869-z.

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Not yet recruitingObservational study
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Helena M Verkooijen, MD, PhD principal investigator

Imaging Division, UMC Utrecht

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Hyperbaric oxygen therapy in people with Breast Cancer and Radiation Toxicity, run by UMC Utrecht at 1 site in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in breast/chest wall pain: EORTC QLQ-BR23 questionnaire (time frame: Baseline and 6 months after baseline (i.e. 3 months after HBOT)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04193722, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Apr 2025.