Official Title: “Phase III Randomized, Double-Blind, Placebo-Controlled Evaluation of Citalopram for the Treatment of Hot Flashes”

RATIONALE: Citalopram may help relieve hot flashes in women who had or have not had breast cancer. It is not yet known which dose of citalopram is more effective in treating hot flashes in postmenopausal women.

PURPOSE: This randomized phase III trial is studying three different doses of citalopram to compare how well they work in treating postmenopausal women with hot flashes.

Study Type: Interventional

Study Design: Supportive Care, Randomized, Double-Blind, Placebo Control

OBJECTIVES:

Primary - Evaluate the efficacy of three different doses of citalopram hydrobromide on hot flash scores in postmenopausal women with a history of breast cancer or in postmenopausal women who do not wish to take estrogen replacement therapy for fear of increased risk of breast cancer.

Secondary - Compare the side effect profile of these regimens in these patients. - Compare the effects of these regimens on the secondary outcome of mood and interference with activities from hot flashes. - Determine if CYP2C19 and CYP2D6 polymorphisms predict efficacy of various doses of citalopram hydrobromide.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to age (18-49 years vs ≥ 50 years), tamoxifen (yes vs no), selective estrogen-receptor modulators (SERMs) (yes vs no), aromatase inhibitors (yes vs no), duration of hot flashes (< 9 months vs ≥ 9 months), and frequency of hot flashes per day (< 4 vs 4-9 vs ≥ 10). Patients are randomized to 1 of 4 treatment arms. - Arm I (low-dose citalopram hydrobromide): Patients receive 1 tablet of oral citalopram once daily in weeks 2-7. - Arm II (medium-dose citalopram hydrobromide): Patients receive 1 tablet of oral citalopram once daily in week 2 and 2 tablets once daily in weeks 3-7. - Arm III (high-dose citalopram hydrobromide): Patients receive 1 tablet of oral citalopram once daily in week 2, 2 tablets once daily in week 3, and 3 tablets once daily in weeks 4-7. - Arm IV (placebo): Patients receive 1-3 placebo tablets once daily in weeks 2-7. All patients complete a diary of hot flash incidence in weeks 1-7 and undergo blood collection periodically during study treatment for translational research studies.

A Symptom Experience diary is completed weekly and Profile of Mood States and Hot Flash-Related Interference Scale questionnaires are completed at baseline and in week 7.

PROJECTED ACCRUAL: A total of 220 patients will be accrued for this study.

Intervention(s) in this Clinical Trial

• Drug: citalopram hydrobromide
• Procedure: psychosocial assessment and care
• Procedure: quality-of-life assessment

Primary Measures

• Difference in average hot flash score from baseline until week 7 of treatment

Secondary Measures

• Toxicity
• Mood- and hot flash-related daily interference with activities

DISEASE CHARACTERISTICS:

• Must meet 1 of the following criteria:
• History of breast cancer
• No current malignant disease
• No history of breast cancer and refused estrogen replacement therapy due to perceived increased risk of breast cancer
• Bothersome hot flashes, defined as hot flashes ≥ 14 times/week and of sufficient severity to make the patient desire therapeutic intervention
• Presence of hot flashes ≥ 1 month prior to study entry
• Hormone receptor status not specified

PATIENT CHARACTERISTICS:

• Female
• Postmenopausal, as defined by 1 of the following criteria:
• Absence of a menstrual period in the past 12 months
• Bilateral oophorectomy
• Absence of a menstrual period in the past 6 months with follicle-stimulating hormone (FSH) level > 40 mIU/mL
• ECOG performance status 0-1
• Life expectancy ≥ 6 months
• Willing to provide blood samples during study participation
• No history of allergic or other adverse reactions to citalopram hydrobromide or other selective serotonin reuptake inhibitors (SSRIs)
• No documented mania or hypomania

PRIOR CONCURRENT THERAPY:

• At least 4 weeks since prior and no concurrent antineoplastic chemotherapy
• At least 4 weeks since prior and no concurrent androgens, estrogens, or progestational agents
• At least 3 months since prior antidepressant use, including Hypericum perforatum (St.
• John's wort)
• Concurrent tamoxifen, raloxifene, or aromatase inhibitors allowed if on a constant dose for ≥ 4 weeks and continuing medication during study period
• No other concurrent or planned agents for treating hot flashes (e.g., phenobarbital, megestrol, or clonidine)
• Stable dose of vitamin E allowed as long as it was started > 30 days prior to study entry
• Concurrent soy allowed
• Concurrent gabapentin allowed for reasons other than hot flashes if on a constant dose for ≥ 1 month and continuing during study period

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: North Central Cancer Treatment Group

Overall Clinical Trial Officials and Contacts

Debra Barton, RN, PhD, AOCN  Mayo Clinic  

Information obtained from ClinicalTrials.gov on November 19, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00363909

Study ID Number: CDR0000489567

ClinicalTrials.gov Identifier: NCT00363909

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database