Amiloride hydrochloride, furosemide for ER-positive, HER2-negative breast cancer (stages I–II) | ER-positive, HER2-negative breast cancer (stages I–III)

Inclusion criteria

• {"criterion_text":"- Female (both pre- and postmenopausal) or male patients\n- Completed baseline assessment of patient-reported questionnaires (EORTC QLQ-C30 and EORTC QLQ-BR42)\n- Before patient registration, written informed consent must be given according to ICH/GCP, and national/local regulations\n- Patients of childbearing / reproductive potential must agree to use at least one highly effective contraceptive measure until treatment discontinuation\n- 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.\n- A breastfeeding patient should discontinue nursing prior to the first dose of study treatment and until 1 month after the last study treatment\n- Age ≥18 years\n- Ongoing adjuvant ET for ER positive HER2 negative breast cancer stages I-III\n- Patients must have received at least 3 months and up to 3 years of ET and planned to continue the same ET during the study\n- Adjuvant cyclin dependent kinase 4 and 6 (CDK4/6) inhibitor or poly ADP ribose polymerase (PARP) inhibitor treatment is allowed as long as they are planned to be kept during the study duration\n- 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\n- Previous chemotherapy is allowed if completed at least 3 months before enrolment\n- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2\n- Adequate organ function as defined below: • Glomerular filtration rate estimated via the MDRD equation of ≥ 30 mL/min/1.73m2 • Potassium levels ≥ 3.0 mmol/L • Sodium levels ≥ 130 mmol/L • Total bilirubin <1.5 times the upper limit of normal (ULN) (< 3 times the upper limit of normal for Gilbert’s disease)"}

Exclusion criteria

• {"criterion_text":"- Current history of grade ≥ 2 CTCAE V5.0 depression and/or anxiety\n- Known difficulty in tolerating oral medications or conditions which would impair absorption of oral medications\n- Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol, understanding and completion of questionnaires and follow-up schedule\n- Participation in another interventional study with systemic drugs\n- History of suicide-related events\n- Current use of diuretics, antidepressants and irreversible monoamine oxidase inhibitors (MAOIs)\n- Current use of prescribed or natural medicines with known interactions with furosemide and/or duloxetine\n- Uncontrolled high blood pressure defined as systolic ≥150 mmHg and ≥ diastolic 100 mmHg\n- Symptomatic hypotension, hypovolemia, or dehydration\n- Addison’s disease\n- Porphyria\n- Uncontrolled intercurrent illness, including psychiatric conditions, chronic alcoholism, and drug addiction"}

Primary endpoints

• {"endpoint_text":"- Change from baseline in the skeletal scale as assessed by the EORTC QLQ-BR42 at month 3. • The skeletal scale score is computed based on the following four individual items from the EORTC QLQ-BR42 questionnaire Have you had problems with your joints? • Have you had stiffness in your joints? • Have you had pain in your joints? • Have you had aches or pains in your bones?","definition_or_measurement_approach":"Change from baseline in the EORTC QLQ-BR42 skeletal scale at month 3; the skeletal scale score is computed from four EORTC QLQ-BR42 items relating to joint problems, joint stiffness, joint pain and bone aches/pains."}

Secondary endpoints

• {"endpoint_text":"- Discontinuation of endocrine therapy","definition_or_measurement_approach":"Rate of discontinuation of endocrine therapy in each arm compared to standard arm (as stated)."}
• {"endpoint_text":"- Change from baseline in the skeletal scale as assessed by the EORTC QLQ-BR42 questionnaire at month 6","definition_or_measurement_approach":"Change from baseline in the EORTC QLQ-BR42 skeletal scale at month 6."}
• {"endpoint_text":"- Change from baseline in Global health status/QoL scale according to EORTC-QLQ-C30 questionnaire at 3 and 6 months","definition_or_measurement_approach":"Change from baseline in global health status/quality of life per EORTC QLQ-C30 at months 3 and 6."}
• {"endpoint_text":"- Change from baseline in Emotional functioning scale according to EORTC-QLQ-C30 questionnaire at 3 and 6 months","definition_or_measurement_approach":"Change from baseline in emotional functioning scale of EORTC QLQ-C30 at months 3 and 6."}
• {"endpoint_text":"- Change from baseline Endocrine therapy symptoms scale according to EORTC-BR42 questionnaire at 3 and 6 months","definition_or_measurement_approach":"Change from baseline in the endocrine therapy symptoms scale of EORTC QLQ-BR42 at months 3 and 6."}
• {"endpoint_text":"- Safety according to the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 5.0 for toxicity and Serious Adverse Event reporting","definition_or_measurement_approach":"Adverse events and serious adverse events graded and reported according to CTCAE v5.0."}

Cyprus

Earliest CTIS Part Ii Submission Date

31-01-2025

Latest Decision Or Authorization Date

17-02-2025

Processing Time Days

17

Number Of Sites

1

Number Of Participants

13

France

Earliest CTIS Part Ii Submission Date

04-12-2024

Latest Decision Or Authorization Date

17-02-2025

Processing Time Days

75

Number Of Sites

3

Number Of Participants

40

Slovenia

Earliest CTIS Part Ii Submission Date

17-10-2024

Latest Decision Or Authorization Date

17-02-2025

Processing Time Days

123

Number Of Sites

1

Number Of Participants

31

Spain

Earliest CTIS Part Ii Submission Date

31-01-2025

Latest Decision Or Authorization Date

11-02-2025

Processing Time Days

11

Number Of Sites

3

Number Of Participants

148

Poland

Earliest CTIS Part Ii Submission Date

30-01-2025

Latest Decision Or Authorization Date

17-02-2025

Processing Time Days

18

Number Of Sites

1

Number Of Participants

20

Primary sponsor

Full Name

Europese Organisatie Voor Onderzoek En Behandeling Van Kanker Organisation Europeenne Pour La Recherche Et Le Traitement Du Cancer European Organi

Organisation Type

Patient organisation/association

Country Of Registered Address

Belgium