Improvement of Quality of Life Through Supportive Treatments for Hormone Therapy - Related Symptoms in Patients With Early Breast Cancer

Improvement of Quality of Life Through Supportive Treatments for Hormone Therapy - Related Symptoms in Patients With Early Breast Cancer; A Pragmatic Randomized Controlled Trial

This study is a pragmatic international, multicenter, randomized, open label 3- arm trial of standard care vs. two pharmacological interventions: duloxetine or furosemide in patients with stage I-III ER+/HER2- early breast cancer with joint, muscle and/or bone pain caused by the endocrine therapy.

The purpose of the BC-QOL trial is to find out whether treatment with duloxetine or furosemide, given while patients are on treatment with endocrine therapy, is active in improving quality of life (QoL), specifically by improving joint, muscle and/or bone pain caused by the endocrine therapy (based on EORTC QLQ-BR42 skeletal scale).

Study Overview

• Status: Not yet recruiting
• Conditions: Musculoskeletal Pain; Drug-Related Side Effects and Adverse Reactions; Breast Cancer Stage I; Breast Cancer Stage II; Breast Cancer Stage III; HER2-negative Breast Cancer; ER+ Breast Cancer
• Intervention / Treatment: Behavioral: Booklet for healthy behaviors; Drug: Duloxetine 60 MG; Drug: Furosemide 40 mg

Detailed Description

Patients, identified by their clinicians as suffering from Grade 2 or above endocrine therapy-related musculoskeletal symptoms [joint/bone/muscle pain]) for, at least, 4 weeks before enrolment will be centrally randomized 1:1:1 between:

• Control arm: Standard of care (SoC) including a booklet focused on healthy behaviors
• Experimental arm: Duloxetine 60 mg (1 pill a day) + SoC
• Experimental arm: Furosemide 40 mg (1 pill a day) + SoC

Treatment duration will be 6 months. All patients will receive usual care, including a booklet focused on healthy behaviors, particularly physical exercise, to manage endocrine therapy side-effects. Treatment administration and modifications as well as specific monitoring should be done in accordance to the SmPC of the corresponding drugs.

• Study Type: Interventional
• Enrollment (Estimated): 399
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: EORTC HQ; Phone Number: +3227741611; Email: eortc@eortc.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

• Female (both pre- and postmenopausal) or male patients
• Age ≥18 years
• Ongoing adjuvant ET (tamoxifen or OFS plus tamoxifen or OFS plus AI or AI ) for ER positive HER2 negative breast cancer stages I-III
• Patients must have received at least 3 months and up to 3 years of ET and planned to continue ET during the study conduction

• Present endocrine therapy related MSK pain (arthralgia and/or bone pain and/or myalgias), evaluated by the treating clinician as at least grade 2 CTCAE V5.0 for, at least, 4 weeks before enrolment, at the time of the clinic visit:

  • Grade 2: moderate pain; limiting instrumental activities daily living (ADL)
  • Grade 3: severe pain; limiting activities self-care ADL
• Previous chemotherapy is allowed if completed at least 3 months before enrolment
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2
• Adequate organ function
• Completed baseline assessment of patient-reported questionnaires (EORTC QLQ-C30 and EORTC QLQ breast module)
• Before patient registration, written informed consent must be given according to ICH/GCP, and national/local regulations
• Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 7 days prior to the first dose of study treatment.

Note: women of childbearing potential are defined as premenopausal females capable of becoming pregnant (i.e., females who have had any evidence of menses in the past 12 months, except for those who had prior hysterectomy). However, women who have been amenorrhoeic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antioestrogens, low body weight, ovarian suppression, or other reasons.

• Patients of childbearing / reproductive potential must agree to use at least one acceptable effective contraceptive measure until treatment discontinuation.
• Female subjects who are breast feeding should discontinue nursing prior to the first dose of study treatment and until 1 month after the last study treatment.

Exclusion criteria:

• Current history of moderate/severe depression and/or anxiety, both defined as grade≥2 CTCAE V5.0
• History of suicide-related events
• Current use of diuretics, antidepressants and/or phytoestrogens
• Current use of prescribed or natural medicines with known interactions with furosemide and/or duloxetine

• Contraindications to duloxetine:

  • Severe renal impairment (creatinine clearance < 30 mL/min)
  • Uncontrolled hypertension
  • Hepatic impairment Child Pugh Class B or C

• Contraindications to furosemide:

  • Symptomatic hypotension, hypovolemia, or dehydration
  • Severe renal impairment (creatinine clearance < 30 mL/min)
  • Severe hypokalaemia and/or severe hyponatremia
  • Addison's disease
  • Porphyria
• Uncontrolled intercurrent illness, including psychiatric conditions, chronic alcoholism, and drug addiction, that would, in the judgment of the investigator, limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
• Known difficulty in tolerating oral medications or conditions which would impair absorption of oral medications such as: uncontrolled nausea or vomiting (i.e., CTCAE ≥ Grade 3 despite antiemetic therapy), ongoing gastrointestinal obstruction/motility disorder, malabsorption syndrome, or prior gastric bypass
• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol, understanding and completion of questionnaires and follow-up schedule; those conditions should be assessed and discussed with the patient before the enrolment in the trial.
• Participation in another interventional study with drugs.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control arm (SoC); Standard of care (SoC) including a booklet focused on healthy behaviors	Behavioral: Booklet for healthy behaviors; All patients will receive usual care, including a booklet focused on healthy behaviors, particularly physical exercise, to manage endocrine therapy side-effects.
Experimental: Experimental arm SoC with duloxetine; Duloxetine 60 mg (1 pill a day) + SoC	Behavioral: Booklet for healthy behaviors; All patients will receive usual care, including a booklet focused on healthy behaviors, particularly physical exercise, to manage endocrine therapy side-effects.; Drug: Duloxetine 60 MG; Patients randomized to the duloxetine arm will take duloxetine orally daily, with or without food, on a continuous dosing schedule. Initial dose is 30 mg daily for 1 week, followed by 60 mg daily for a total of 6 months of treatment, followed by a taper off the medication of 30 mg daily for 1 additional week.
Experimental: Experimental arm SoC with Furosemide; Furosemide 40 mg (1 pill a day) + SoC	Behavioral: Booklet for healthy behaviors; All patients will receive usual care, including a booklet focused on healthy behaviors, particularly physical exercise, to manage endocrine therapy side-effects.; Drug: Furosemide 40 mg; Patients randomized to the furosemide arm will take furosemide 40 mg orally daily, on an empty stomach with plenty of liquid, on a continuous dosing schedule.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endocrine therapy related musculoskeletal pain	Assessed by the Skeletal scale from the EORTC-QLQ-BR42 questionnaire, with the minimum and maximum values being 0 - 100 and higher score means worse outcome.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Discontinuation of endocrine therapy	Proportion of patients who discontinued endocrine therapy	6 months
Endocrine therapy related musculoskeletal pain	Assessed by the Skeletal scale from the EORTC-QLQ-BR42 questionnaire, with the minimum and maximum values being 0 - 100 and higher score means worse outcome.	6 months
Overall quality of life	Assessed by the Global Health status/Quality of Life scale from the EORTC-QLQ-C30 questionnaire, with the minimum and maximum values being 0 - 100 and higher score means better outcome.	3 months and 6 months
Emotional functioning	Assessed by the emotional functioning scale from the EORTC-QLQ-C30 questionnaire, with the minimum and maximum values being 0 - 100 and higher score means better outcome.	3 months and 6 months
Endocrine therapy related symptoms	Assessed by the endocrine therapy symptom scale from the EORTC-QLQ-BR42 questionnaire, with the minimum and maximum values being 0 - 100 and higher score means worse outcome.	3 months and 6 months

Collaborators and Investigators

• Sponsor: European Organisation for Research and Treatment of Cancer - EORTC

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2024
• Primary Completion (Estimated): April 18, 2028
• Study Completion (Estimated): November 30, 2028

Study Registration Dates

• First Submitted: May 6, 2024
• First Submitted That Met QC Criteria: May 6, 2024
• First Posted (Actual): May 9, 2024

Study Record Updates

• Last Update Posted (Estimated): November 5, 2024
• Last Update Submitted That Met QC Criteria: November 4, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Quality of Life
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neoplasms by Site; Neoplasms; Chemically-Induced Disorders; Skin Diseases; Breast Diseases; Musculoskeletal Pain; Breast Neoplasms; Drug-Related Side Effects and Adverse Reactions; Serotonin and Noradrenaline Reuptake Inhibitors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Sensory System Agents; Analgesics; Neurotransmitter Agents; Membrane Transport Modulators; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Dopamine Agents; Antidepressive Agents; Diuretics; Natriuretic Agents; Sodium Potassium Chloride Symporter Inhibitors; Duloxetine Hydrochloride; Furosemide
• Other Study ID Numbers: EORTC-2237-BCG-QLG

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No