Oxybutynin Chloride in Managing Hot Flashes

Breast Carcinoma Clinical Trial

Official title:

A Phase III, Double-Blind, Controlled Trial of Oxybutynin in the Management of Hot Flashes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02961790
• Other study ID #: ACCRU-SC-1603
• Secondary ID: NCI-2016-01603AC
• Status: Completed
• Phase: Phase 3
• Start date: December 9, 2016
• Est. completion date: April 27, 2018

Study information

• Verified date: August 2018
• Source: Academic and Community Cancer Research United
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized phase III trial studies how well oxybutynin chloride works in managing hot flashes in patients who are not candidates for, or not interested in hormone replacement therapy. Previous studies have shown that oxybutynin is effective in managing hot flashes, however doses used in prior studies have resulted in side effects. This trial is evaluating lower doses of oxybutynin with the goal of determining if they are efficacious with less side effects.

ADAM-VTE

Description:

PRIMARY OBJECTIVES:

I. To determine whether oxybutynin chloride (oxybutynin) can diminish hot-flash activity in women with a history of breast cancer or in women who have a concern about taking estrogen for fear of breast cancer.

SECONDARY OBJECTIVES:

I. To perform a dose-response evaluation of two oxybutynin doses. II. To determine the toxicity of oxybutynin in the study population. III. To assess the impact of hot-flash activity on overall quality of life and to examine whether oxybutynin can diminish this impact on quality of life.

OUTLINE: Patients are randomized into 1 of 4 groups.

GROUP I (LOW-DOSE OXUBUTYNIN CHLORIDE): Patients receive lower dose oxybutynin chloride orally (PO) twice a day (BID) on days 8-49 in the absence of unacceptable toxicity.

GROUP II (LOW-DOSE PLACEBO): Patients receive lower dose placebo PO BID on days 8-49 in the absence of unacceptable toxicity.

GROUP III (HIGH-DOSE OXUBUTYNIN CHLORIDE): Patients receive lower dose oxybutynin chloride PO BID on days 8-14 and higher dose oxybutynin chloride on days 15-49 in the absence of unacceptable toxicity.

GROUP IV (HIGH-DOSE PLACEBO): Patients receive lower dose placebo PO BID on days 8-14 and higher dose placebo on days 15-49 in the absence of unacceptable toxicity.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: April 27, 2018
• Est. primary completion date: April 27, 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• History of breast cancer, ductal breast carcinoma in situ (DCIS), or lobular carcinoma in situ (LCIS) (currently without evidence of malignant disease) OR a concern about taking estrogen for fear of breast cancer

• Bothersome hot flashes (defined by their occurrence of >= 28 times per week and of sufficient severity to prompt the patient to seek therapeutic intervention)

• Presence of hot flashes for > 30 days prior to study entry

• Ability to complete questionnaire(s) by themselves or with assistance

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) = 0, 1

• Ability to provide informed written consent

• Life expectancy >= 6 months

• Willing to work with the enrolling institution for follow-up (during the active monitoring phase of the study)

Exclusion Criteria:

• Any of the following current (=< 4 weeks prior) or planned therapies:

• Antineoplastic chemotherapy (anti-HER2 agents allowed)

• Androgens

• Estrogens (any delivery route)

• Progestogens

• Tamoxifen, raloxifene and aromatase inhibitors are allowed, but patient must have been on a constant dose for at least 28 days and must not be expected to stop the medication during the study period

• Selective serotonin reuptake inhibitors (SSRIs)/serotonin?norepinephrine reuptake inhibitors (SNRIs), when being used for hot flash management or other indications such as depression, is allowed, assuming the dose will remain unchanged for the study duration

• Gabapentin/pregabalin, when being used for hot flash management (use for other indications, such as pain, is allowed, assuming the dose will remain unchanged for the study duration)

• Clonidine

• Agents with known potent anticholinergic activity; agents with mild-moderate anticholinergic activity are allowed

• Prior use of oxybutynin during the period in which patient has had hot flashes

• Pregnant women

• Nursing women

• History of any of the following contraindications to oxybutynin:

• Uncontrolled gastroesophageal reflux disease (GERD) despite appropriate therapy; if patient has history of GERD, but symptoms are well-controlled with medical treatment, patient is eligible

• Ulcerative colitis

• Narrow-angle glaucoma

• Urinary retention

• Hypersensitivity to oxybutynin or any other components of the product

• Current uncontrolled hyperthyroidism

• Coronary heart disease (angina or prior myocardial infarction)

• Congestive heart failure

• Symptomatic cardiac arrhythmias

• Current uncontrolled hypertension

• Myasthenia gravis

• Dementia

Related Conditions & MeSH terms

• Breast Carcinoma
• Breast Carcinoma In Situ
• Breast Neoplasms
• Carcinoma
• Carcinoma in Situ
• Carcinoma, Ductal, Breast
• Carcinoma, Intraductal, Noninfiltrating
• Carcinoma, Lobular
• Ductal Breast Carcinoma In Situ
• Hot Flashes
• Lobular Breast Carcinoma In Situ
• No Evidence of Disease

Intervention

Drug:
• Oxybutynin Chloride
Given PO

Other:
• Placebo
Given PO
• Quality-of-Life Assessment
Ancillary studies
• Questionnaire Administration
Ancillary studies

Locations

Country	Name	City	State
United States	AnMed Health Cancer Center	Anderson	South Carolina
United States	Michigan Cancer Research Consortium NCORP	Ann Arbor	Michigan
United States	Waverly Hematology Oncology	Cary	North Carolina
United States	Oncology Associates at Mercy Medical Center	Cedar Rapids	Iowa
United States	Saint Elizabeth Medical Center South	Edgewood	Kentucky
United States	Saint Vincent Hospital -Green Bay	Green Bay	Wisconsin
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	Marshfield Clinic	Marshfield	Wisconsin
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	Mayo Clinic	Rochester	Minnesota
United States	Carle Cancer Center NCI Community Oncology Research Program	Urbana	Illinois
United States	Cancer Center of Kansas - Wichita	Wichita	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
Academic and Community Cancer Research United	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Average Change in Hot Flash Activity Score From Baseline to Week 7 for Low Dose Oxybutynin vs Placebo and for High Dose Oxybutynin vs Placebo	Average change in hot flash activity score from baseline to Week 7 for Low Dose Oxybutynin vs Placebo. The hot flash activity will be measured by the weekly average hot flash score (Sloan JA, et. al., 2001), which is a composite entity of both frequency and severity of hot flashes (The Hot Flash Diary collects the following information for Day 1- Day 7 of each week: Number of mild hot flashes, Number of moderate hot flashes, Number of severe hot flashes, Number of very severe hot flashes). This is a count, so it can range from 0 to infinity.	Baseline up to day 49
Secondary	Average Change in Hot Flash Score From Week 1 to Week 7 Comparing Low Dose Oxybutynin to Placebo	Average change in Hot Flash Score from Week 1 to Week 7 Comparing Low Dose Oxybutynin to Placebo. The least squares (LS) mean was estimated from a mixed-effects model with repeated measures (MMRM) that included low dose oxybutynin, weeks 1-7, no current aromatase inhibitor, age group 18-49, no tamoxifen, hot flash symptom duration < 9 months, and 4-9 hot flashes/day as fixed effects, and participant and error as random effects. The mean change in Hot Flash Score from Week 1 to Week 7 is reported below for the low-dose oxybutynin and placebo groups.	Baseline up to day 49
Secondary	Average Change in Hot Flash Score From Week 1 to Week 7 Comparing High Dose Oxybutynin to Placebo	Average change in Hot Flash Score from Week 1 to Week 7 Comparing High Dose Oxybutynin to Placebo. The least squares (LS) mean was estimated from a mixed-effects model with repeated measures (MMRM) that included low dose oxybutynin, weeks 1-7, no current aromatase inhibitor, age group 18-49, no tamoxifen, hot flash symptom duration < 9 months, and 4-9 hot flashes/day as fixed effects, and participant and error as random effects. The mean change in Hot Flash Score from Week 1 to Week 7 is reported below for the high-dose oxybutynin and placebo groups.	Baseline up to day 49
Secondary	Average Change of Severity of Stomach Pain/Cramps Symptoms as Measured by the Symptom Experience Questionnaire From Baseline to Week 7 for Low Dose Oxybutynin vs Placebo and for High Dose Oxybutynin vs Placebo	Average Change of severity of Stomach pain/cramps symptoms as measured by the Symptom Experience Questionnaire From Baseline to Week 7 for Low Dose Oxybutynin vs Placebo and for High Dose Oxybutynin vs Placebo The Symptom Experience Questionnaire stomach pain/cramps item ("Over the past week, have you experienced stomach pain or cramps?") is scored from 0 to 10 with higher values being worse symptoms. So a negative value means the symptom is improving and a positive score means the symptom is getting worse.	Baseline up to day 49
Secondary	Average Change of Daily Interference (Work) From Baseline to Week 7 as Measured by the Hot Flash-Related Daily Interference Scale (HFRDIS) Comparing Low Dose Oxybutynin vs Placebo and High Dose Oxybutynin vs Placebo	Average Change of daily interference (Work) from baseline to Week 7 as measured by the Hot Flash-Related Daily Interference Scale (HFRDIS) comparing Low dose oxybutynin vs Placebo and High dose oxybutynin vs Placebo. HFRDIS Work item ("Work (work outside the home and housework)") Interference scores run from 0 to 10 with 0 being no interference and 10 being complete interference.	Baseline up to day 49
Secondary	Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4)	The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns within patient groups. In addition, we will review all adverse event data that is graded as 3, 4, or 5 and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing. The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below.	Up to 7 weeks