Desvenlafaxine for Treatment of Hot Flashes in Women With Breast Cancer Taking Tamoxifen

Desvenlafaxine for the Treatment of Hot Flashes in Women With Breast Cancer Taking Tamoxifen: a Randomized, Double-blind, Placebo-controlled Study

This study is a randomized, placebo-controlled study of desvenlafaxine versus placebo. The purpose of this study is to determine if desvenlafaxine was effective in decreasing the frequency and severity of hot flashes in breast cancer patients taking tamoxifen.

Study Overview

• Status: Terminated
• Conditions: Breast Neoplasms; Hot Flashes
• Intervention / Treatment: Drug: Placebo; Drug: Desvenlafaxine succinate 100mg; Drug: Desvenlafaxine succinate 50mg

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Gyeonggi-do
    • Goyang, Gyeonggi-do, Korea, Republic of, 10408
      • National Cancer Center
    • Seongnam, Gyeonggi-do, Korea, Republic of, 13620
      • Seoul National University Bundang Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

i. Women age 18 years and older with localized breast cancer. Histologic documentation of atypical ductal hyperplasia, ductal carcinoma in situ (DCIS), lobular carcinoma in situ (LCIS), or invasive adenocarcinoma of the breast stages I-III A.

ii. Current daily tamoxifen use (≥ 6 days/week). Any planned surgery, adjuvant chemotherapy or radiation must have been completed.

iii. History of bothersome hot flushes: ≥ 14 hot flushes/week (average ≥ 2 hot flushes/day), sufficiently severe that intervention is desired. Participants must have had bothersome hot flushes for at least one month prior to enrollment.

Exclusion Criteria:

i. Women who is pregnant or breast feeding, or who has a history of seizure disorder or hepatic or renal insufficiency ii. Concurrent systemic hormone replacement therapy (estrogen, progestational agents, androgens) or use of corticosteroids iii. Concurrent use of other antidepressants, anxiolytics and antipsychotics, gabapentin, pregabalin and clonidine for treatment of hot flushes or depression.

iv. Presense or past history of severe psychiatric symptoms such as hallucinations and delusions, manic episodes, or high suicide risk.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Desvenlafaxine succinate 100mg; Titration with 50 mg Desvenlafaxine succinate tablet once daily for 1 week, then 2 tablets of 50mg Desvenlafaxine succinate tablet once daily for 3 weeks, then taper with 50 mg Desvenlafaxine succinate tablet once daily for 3 days.	Drug: Desvenlafaxine succinate 100mg; Pristiq 100mg
Experimental: Desvenlafaxine succinate 50mg; 50 mg Desvenlafaxine succinate tablet once daily for 1 week, then 1 tablets of 50mg Desvenlafaxine succinate tablet and 1 tablet of 50mg placebo tablet once daily for 3 weeks, then 50mg placebo tablet once daily for 3 days.	Drug: Desvenlafaxine succinate 50mg; Pristiq 50mg
Placebo Comparator: Placebo; 50 mg placebo tablet once daily for 1 week, then 2 tablets of 50mg placebo tablet once daily for 3 weeks, then 50 mg placebo tablet once daily for 3 days.	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction rate of hot flashes symptom score	Participants would complete self -report daily diary on which they record the number and severities (1 - 4 points) of hot flashes from baseline to week 5. Each symptom severities are multiplied by the numbers of symptoms to determine the daily hot flashes symptom score. The mean of daily hot flashes symptom score of one week is calculated and regared as a hot flashes symptom score for the week. The efficacy of Desvenlafaxine is assessed by comparing the reduction rate of weekly hot flashes symptom score (= hot flashes symptom score at week 5 - hot flashes symptom score at baseline / hot flashes symptom score of baseline) for each group.	From baseline to Week 5 (Intervention is started from Week 1)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical impression state and change	Clinical global impression (CGI) would be used to assess clinical impression state and change.	Week 1, Week 2, Week 5
Peripheral neuropathy	European Organization for Research and Treatment of Cancer - Quality of Life Questionnaire - Chemotherapy-Induced Peripheral Neuropathy(EORTC-QLQ-CIPN-20) would be used to assess peripheral neuropathy.	Week 1, Week 2, Week 5
Depression	Patient health questionnaire (PHQ-9) would be used to assess mood status.	Baseline, Week 2, Week 5
Anxiety	Generalized anxiety disorder-7 (GAD-7) would be used to assess anxiety.	Baseline, Week 2, Week 5
Manic or Hypomanic symptoms.	Mood disorder questionnaire (MDQ) would be used to assess manic or hypomanic symptoms.	Baseline, Week 2, Week 5
Sleep quality	Pittsburgh sleep quality index (PSQI) would be used to assess sleep quality.	Baseline, Week 2, Week 5
Chonotype	Morningness-Eveningness questionnaire (MEQ) would be used to assess chronotype.	Baseline
Circadian misalignment	Munich Chronotype Questionnaire (MCTQ) would be used to assess circadian misalignment.	Baseline, Week 2, Week 5
Fatigue	Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-fatigue) would be used to assess fatigue.	Baseline, Week 2, Week 5
Quality of life	Functional Assessment of Cancer Therapy-Breast (FACT-B) would be used to assess quality of life.	Baseline, Week 2, Week 5
Beliefs about medicines	Beliefs about Medicines Questionnaire (BMQ) would be used to assess beliefs about medicines.	Baseline
Illness perception	Brief Illness Perception Questionnaire (BIPQ) would be used to assess illness perception.	Baseline
Social support	Multidimensional Scale of Perceived Social Support (MSPSS) would be used to assess social supports.	Baseline
Body image	Body Image Scale (BIS) would be used to assess body image.	Baseline
Resilience	Connor-Davidson Resilience Scale (CDRS) would be used to assess resilience.	Baseline
Hormonal level	Serum estradiol, follicle-stimulating hormone (FSH) and anti-Müllerian hormone (AMH) levels would be used to examine pathophysiological mechanisms associated with the presence of hot flashes, mood status and desvenlafaxine treatment.	Week 2
Genetic polymorphism	estrogen receptors (ESR1 PvuII; rs#2234693 and XbaI; rs#9340799 and ESR2-02; rs#4986938) and serotonin transporter gene (SLC6A4; rs#11080121) would be used to examine pathophysiological mechanisms associated with the presence of hot flashes, mood status and desvenlafaxine treatment.	Week 2

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Collaborators: Pfizer; Seoul National University Bundang Hospital; Korea Cancer Center Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2017
• Primary Completion (Actual): March 15, 2019
• Study Completion (Actual): June 15, 2019

Study Registration Dates

• First Submitted: June 24, 2016
• First Submitted That Met QC Criteria: June 28, 2016
• First Posted (Estimate): June 30, 2016

Study Record Updates

• Last Update Posted (Actual): September 20, 2019
• Last Update Submitted That Met QC Criteria: September 18, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Tamoxifen; Breast Neoplasms; Hot Flashes; Desvenlafaxine Succinate
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Hot Flashes; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Serotonin and Noradrenaline Reuptake Inhibitors; Desvenlafaxine Succinate
• Other Study ID Numbers: WI209149

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No