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Oxybutynin Chloride in Managing Hot Flashes

Primary Purpose

Breast Carcinoma, Ductal Breast Carcinoma In Situ, Hot Flashes

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Oxybutynin Chloride
Placebo
Quality-of-Life Assessment
Questionnaire Administration
Sponsored by
Academic and Community Cancer Research United
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Breast Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • Illinois CancerCare-Peoria
  • Carle Cancer Center NCI Community Oncology Research Program
  • Oncology Associates at Mercy Medical Center
  • Cancer Center of Kansas - Wichita
  • Saint Elizabeth Medical Center South
  • Michigan Cancer Research Consortium NCORP
  • Mayo Clinic
  • Waverly Hematology Oncology
  • AnMed Health Cancer Center
  • Rapid City Regional Hospital
  • Saint Vincent Hospital -Green Bay
  • University of Wisconsin Hospital and Clinics
  • Marshfield Clinic

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

Group I (low-dose oxybutynin chloride)

Group II (low-dose placebo)

Group III (high-dose oxybutynin chloride)

Group IV (high-dose placebo)

Arm Description

Patients receive lower dose oxybutynin chloride PO BID on days 8-49 in the absence of unacceptable toxicity.

Patients receive lower dose placebo PO BID on days 8-49 in the absence of unacceptable toxicity.

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.

Full Information

First Posted
November 9, 2016
Last Updated
January 14, 2020
Sponsor
Academic and Community Cancer Research United
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT02961790
Brief Title
Oxybutynin Chloride in Managing Hot Flashes
Official Title
A Phase III, Double-Blind, Controlled Trial of Oxybutynin in the Management of Hot Flashes
Study Type
Interventional

2. Study Status

Record Verification Date
August 2018
Overall Recruitment Status
Completed
Study Start Date
December 9, 2016 (Actual)
Primary Completion Date
April 27, 2018 (Actual)
Study Completion Date
April 27, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Academic and Community Cancer Research United
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Carcinoma, Ductal Breast Carcinoma In Situ, Hot Flashes, Lobular Breast Carcinoma In Situ, No Evidence of Disease

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
150 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group I (low-dose oxybutynin chloride)
Arm Type
Experimental
Arm Description
Patients receive lower dose oxybutynin chloride PO BID on days 8-49 in the absence of unacceptable toxicity.
Arm Title
Group II (low-dose placebo)
Arm Type
Placebo Comparator
Arm Description
Patients receive lower dose placebo PO BID on days 8-49 in the absence of unacceptable toxicity.
Arm Title
Group III (high-dose oxybutynin chloride)
Arm Type
Experimental
Arm Description
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.
Arm Title
Group IV (high-dose placebo)
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Oxybutynin Chloride
Other Intervention Name(s)
Ditropan, Gelnique, MJ-4309-1, Oxybutynin Hydrochloride
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
Placebo
Other Intervention Name(s)
placebo therapy, PLCB, sham therapy
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
Quality-of-Life Assessment
Other Intervention Name(s)
Quality of Life Assessment
Intervention Description
Ancillary studies
Intervention Type
Other
Intervention Name(s)
Questionnaire Administration
Intervention Description
Ancillary studies
Primary Outcome Measure Information:
Title
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
Description
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.
Time Frame
Baseline up to day 49
Secondary Outcome Measure Information:
Title
Average Change in Hot Flash Score From Week 1 to Week 7 Comparing Low Dose Oxybutynin to Placebo
Description
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.
Time Frame
Baseline up to day 49
Title
Average Change in Hot Flash Score From Week 1 to Week 7 Comparing High Dose Oxybutynin to Placebo
Description
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.
Time Frame
Baseline up to day 49
Title
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
Description
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.
Time Frame
Baseline up to day 49
Title
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
Description
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.
Time Frame
Baseline up to day 49
Title
Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4)
Description
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.
Time Frame
Up to 7 weeks

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Charles Loprinzi
Organizational Affiliation
Academic and Community Cancer Research United
Official's Role
Principal Investigator
Facility Information:
Facility Name
Illinois CancerCare-Peoria
City
Peoria
State/Province
Illinois
ZIP/Postal Code
61615
Country
United States
Facility Name
Carle Cancer Center NCI Community Oncology Research Program
City
Urbana
State/Province
Illinois
ZIP/Postal Code
61801
Country
United States
Facility Name
Oncology Associates at Mercy Medical Center
City
Cedar Rapids
State/Province
Iowa
ZIP/Postal Code
52403
Country
United States
Facility Name
Cancer Center of Kansas - Wichita
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67214
Country
United States
Facility Name
Saint Elizabeth Medical Center South
City
Edgewood
State/Province
Kentucky
ZIP/Postal Code
41017
Country
United States
Facility Name
Michigan Cancer Research Consortium NCORP
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48106
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Waverly Hematology Oncology
City
Cary
State/Province
North Carolina
ZIP/Postal Code
27518
Country
United States
Facility Name
AnMed Health Cancer Center
City
Anderson
State/Province
South Carolina
ZIP/Postal Code
29621
Country
United States
Facility Name
Rapid City Regional Hospital
City
Rapid City
State/Province
South Dakota
ZIP/Postal Code
57701
Country
United States
Facility Name
Saint Vincent Hospital -Green Bay
City
Green Bay
State/Province
Wisconsin
ZIP/Postal Code
54301
Country
United States
Facility Name
University of Wisconsin Hospital and Clinics
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
Facility Name
Marshfield Clinic
City
Marshfield
State/Province
Wisconsin
ZIP/Postal Code
54449
Country
United States

12. IPD Sharing Statement

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Oxybutynin Chloride in Managing Hot Flashes

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