Clinical trial NCT05637671: Efficacy and Safety of Oxybutynin Versus Paroxetine in Aromatase Inhibitor-induced Vasomotor Symptoms
Official title: Efficacy and Safety of Oxybutynin Versus Paroxetine in Breast Cancer Patients With Aromatase Inhibitor-induced Vasomotor Symptoms.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Vasomotor Symptoms
Keywords: Hot flashes
vasomotor symptoms
oxybutynin
paroxetine
aromatase inhibitors
breast cancer
Lead sponsor: Cairo University
Sponsor class: OTHER
First posted: 2022-12-05
Enrollment: 146
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Breast cancer is the most prevalent cancer type worldwide. In Egypt, It is the second most common type of cancer and the most common one in women with about 22 thousand new cases in 2020. Around 70% of newly diagnosed patients are hormone receptor-positive and, unfortunately, the disease is often diagnosed at the advanced stage.

In postmenopausal women with hormone receptor-positive breast cancer, aromatase inhibitors (AIs) are the first-line adjuvant therapy according to National Comprehensive Cancer Network (NCCN) guidelines. Although, they showed superiority in efficacy to tamoxifen in this type of breast cancer, one of the most annoying adverse effects of the aromatase inhibitors are the vasomotor symptoms. They could be as severe as the patient would prefer discontinuing the medication. The underlying mechanism responsible for those adverse effects is that AIs suppress plasma estrogen levels by inhibiting the enzyme responsible for the conversion of androgens to estrogens in peripheral tissues. This estrogen depletion has been linked to an increase in hot flushes by decreasing endorphin levels and increasing that of norepinephrine and serotonin, followed by instability of the hypothalamic thermoregulatory set point which allows changes in the body temperature and in hot flash sensation.

Hormone replacement therapy is considered first-line treatment for vasomotor symptoms. However, it is not preferred to be used in breast cancer patients especially those with hormone receptor positive breast cancer. So, many drugs have been investigated for their efficacy in reducing the frequency and severity of vasomotor symptoms. The only FDA-approved drug to treat moderate-to-severe vasomotor symptoms is paroxetine. Paroxetine is a selective serotonin reuptake inhibitor (SSRI) which is used mainly in major depressive disorder and other psychiatric conditions like anxiety disorders. It has proved an efficacy in reducing frequency and severity of hot flushes in post-menopausal women. But, there are several concerns regarding its use with tamoxifen in breast cancer patients. There is a competition between paroxetine and tamoxifen for hepatic CYP2D6, so, paroxetine prevents conversion of tamoxifen into its active metabolite.

Oxybutynin has shown efficacy in relieving vasomotor symptoms. Oxybutynin is an anticholinergic used usually in urinary incontinence. It has an advantage over other SSRIs that it lacks the interaction with tamoxifen on CYP2D6 and, therefore, with the anticancer effect of tamoxifen treatment in breast cancer patients.

To our knowledge, there are no head-to-head studies comparing the efficacy and safety of paroxetine versus oxybutynin in reducing frequency and severity of vasomotor symptoms especially in breast cancer patients taking aromatase inhibitors.


Eligibility criteria: Inclusion Criteria:

1. Post-menopausal female patients who are 18 years of age or older.
2. Patients diagnosed with hormone receptor-positive breast cancer stage 0 - IIIC (non-advanced breast cancer) who are taking aromatase inhibitors as adjuvant therapy (post-surgery) and having Significant vasomotor symptoms, defined as a mean of 5 moderate to severe hot flashes per day.
3. Have an Eastern Cooperative Oncology Group performance status rating (ECOG-PSR) ˂ 2.
4. Life expectancy greater than 6 months.
5. Normal serum creatinine level and bilirubin level is less than two times the normal level.
6. Serum follicle-stimulating hormone (FSH) levels above 40 mIU/mL.

Exclusion Criteria:

1. Patients taking tamoxifen as adjuvant therapy.
2. Metastatic breast cancer.
3. Other treatments used for hot flashes, antidepressants, and monoamine oxidase inhibitors (except if they are discontinued for at least one month before study entry).
4. Hypersensitivity to paroxetine or oxybutynin.
5. Presence of a condition requiring use of an anticholinergic agent.
6. Untreated hypertension.
7. Impaired liver or kidney function.
8. Unstable cardiac disease.
9. Pregnancy or breastfeeding.
10. History of self-injurious behavior.
11. History of clinical diagnosis or treatment of any psychiatric disorder.
12. Prior use of oxybutynin or paroxetine for hot flushes.
13. Recent use of oxybutynin or paroxetine for conditions other than vasomotor symptoms unless they are stopped at least 30 days before the study entry.

Primary outcomes:
measure: Efficacy of oxybutynin compared to paroxetine through hot flashes diary
timeFrame: 12 weeks
measure: Efficacy of oxybutynin compared to paroxetine through The Pittsburgh Sleep Quality Index questionnaire
timeFrame: 12 weeks
Secondary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: 12 weeks
measure: Safety of oxybutynin compared to paroxetine on kidney through serum creatinine assessment
timeFrame: 12 weeks
measure: Safety of oxybutynin compared to paroxetine on kidney through blood urea nitrogen assessment
timeFrame: 12 weeks
measure: Safety of oxybutynin compared to paroxetine on liver through Alanine aminotransferase assessment
timeFrame: 12 weeks
measure: Safety of oxybutynin compared to paroxetine on liver through aspartate aminotransferase assessment
timeFrame: 12 weeks
measure: Safety of oxybutynin compared to paroxetine on liver through bilirubin assessment
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Dar El-Salam Cancer Hospital
state: Governorate
Study officials:
References: