Oxybutynin Chloride in Managing Hot Flashes

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

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

Study Overview

• Status: Completed
• Conditions: Hot Flashes; Breast Carcinoma; Lobular Breast Carcinoma In Situ; Ductal Breast Carcinoma In Situ; No Evidence of Disease
• Intervention / Treatment: Other: Quality-of-Life Assessment; Other: Placebo; Other: Questionnaire Administration; Drug: Oxybutynin Chloride

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Peoria, Illinois, United States, 61615
      • Illinois CancerCare-Peoria
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center NCI Community Oncology Research Program
  • Iowa
    • Cedar Rapids, Iowa, United States, 52403
      • Oncology Associates at Mercy Medical Center
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas - Wichita
  • Kentucky
    • Edgewood, Kentucky, United States, 41017
      • Saint Elizabeth Medical Center South
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • Michigan Cancer Research Consortium NCORP
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • North Carolina
    • Cary, North Carolina, United States, 27518
      • Waverly Hematology Oncology
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • AnMed Health Cancer Center
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Rapid City Regional Hospital
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54301
      • Saint Vincent Hospital -Green Bay
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospital and Clinics
    • Marshfield, Wisconsin, United States, 54449
      • Marshfield Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group I (low-dose oxybutynin chloride); Patients receive lower dose oxybutynin chloride PO BID on days 8-49 in the absence of unacceptable toxicity.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Drug: Oxybutynin Chloride; Given PO; Other Names: Gelnique; Ditropan; MJ-4309-1; Oxybutynin Hydrochloride
Placebo Comparator: Group II (low-dose placebo); Patients receive lower dose placebo PO BID on days 8-49 in the absence of unacceptable toxicity.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Placebo; Given PO; Other Names: placebo therapy; PLCB; sham therapy; Other: Questionnaire Administration; Ancillary studies
Experimental: Group III (high-dose oxybutynin 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.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Drug: Oxybutynin Chloride; Given PO; Other Names: Gelnique; Ditropan; MJ-4309-1; Oxybutynin Hydrochloride
Placebo Comparator: 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.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Placebo; Given PO; Other Names: placebo therapy; PLCB; sham therapy; Other: Questionnaire Administration; Ancillary studies

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Academic and Community Cancer Research United
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Charles Loprinzi, Academic and Community Cancer Research United

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2016
• Primary Completion (Actual): April 27, 2018
• Study Completion (Actual): April 27, 2018

Study Registration Dates

• First Submitted: November 9, 2016
• First Submitted That Met QC Criteria: November 9, 2016
• First Posted (Estimate): November 11, 2016

Study Record Updates

• Last Update Posted (Actual): January 18, 2020
• Last Update Submitted That Met QC Criteria: January 14, 2020
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Breast Diseases; Neoplasms, Ductal, Lobular, and Medullary; Carcinoma, Ductal; Carcinoma in Situ; Breast Neoplasms; Carcinoma; Breast Carcinoma In Situ; Hot Flashes; Carcinoma, Intraductal, Noninfiltrating; Carcinoma, Lobular; Carcinoma, Ductal, Breast; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Urological Agents; Anti-Infective Agents, Urinary; Renal Agents; Oxybutynin; Mandelic Acids
• Other Study ID Numbers: ACCRU-SC-1603 (Other Identifier: Academic and Community Cancer Research United); P30CA015083 (U.S. NIH Grant/Contract); NCI-2016-01603 (Registry Identifier: CTRP (Clinical Trial Reporting Program))