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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Breast Cancer, Radiation Toxicity

Intervention / Treatment
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* Drug: Hyperbaric oxygen therapy


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Trial within cohorts design
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hyperbaric oxygen therapy<br>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<br>* Hyperbaric oxygen therapy in a multiperson hyperbaric oxygen chamber. Standard hyperbaric oxygen therapy provided as reimbursed by insurers.<br>* Other names: Oxygen;|
| No Intervention: Usual care<br>Usual care may consist of physiotherapy, analgetics, edema therapy | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline and 6 months after baseline (i.e. 3 months after HBOT) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 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. | 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. | 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. | 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. | 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. | Baseline and prior to last hyperbaric oxygen session (i.e. 3 months after baseline). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Trials within cohorts, Patient reported outcomes, Breast cancer, Radiotherapy, Hyperbaric oxygen therapy, Late toxicity