Sexual Dysfunction in Gynecologic Oncology Patients
Phase: PHASE4
Conditions: Gynecologic Cancer, Sexual Dysfunction
Sponsor: David Bender

 
 
 
 
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Title: Sexual Dysfunction in Gynecologic Oncology Patients 
 
Principle Investigator: 
David P. Bender, M.D. 
31506 PFP 
200 Hawkins Drive 
University of Iowa Hospitals and Clinics 
Iowa City, IA 52242 
319-356-2015 
319-252-8363 
david-bender@uiowa.edu 
 
Co-Principal Investigator:  
 
Not applicable 
Sub-Investigators:  
 
Michael Goodheart, M.D. 
Jesus Gonzalez-Bosquet, M.D. 
Jean-Marie Stephan, M.D. 
Emily K. Hill, M.D. 
Veronika Kolder, M.D. 
Biostatistician: 
Gideon K.D. Zamba, M.S., Ph.D. 
Primary Research Coordinator: 
Sharon Stockman 
IRB Number: 
201609770 
Version Date: 
01/02/2019 
Version: 
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SCHEMA 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Patients undergoing surgery at UIHC for suspected or diagnosed  
ovarian, fallopian tube, peritoneal, cervical or endometrial cancer 
Consent for study and complete survey packet evaluating sexual dysfunction 
Eligible subjects with a diagnosis of a gynecologic cancer will continue on trial 
12 weeks following primary surgery repeat survey packet evaluating sexual dysfunction 
Randomization 
4% Aqueous lidocaine application                                             Placebo application 
12 weeks after treatment, repeat survey packet and submit 
Visual pain scales and sexual encounter diary 
24 weeks after randomization, repeat survey packet and submit 
Visual pain scales and sexual encounter diary 

 
 
 
 
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REVISION HISTORY 
 
 
Version 1, Version Date November 28, 2016 
 
Version 2, Version Date February 20, 2017 
 
Version 3, Version Date March 24, 2017 
 
Summary of Changes:  
 
1. Version number and date updated 
 
2. Questionnaire revisions: 
 
 
a. Adverse Childhood Experiences questionnaire replaced by accurate  
 
 
 
version. Previously included the International version, which is not  
 
 
 
intended to use.  
 
 
b. Revised Subject Diary with pain scale and sexual encounter log 
 
 
c. Revised Exit Questionnaire – The term “gel” replaced with “solution”  
 
 
    and questions added 
 
Version 4, Version Date May 23, 2017 
 
Summary of Changes: The primary purpose of this amendment is to clarify the 
unblinding procedure.  (Section 5.2.2) 
 
Version 5, Version Date January 2, 2019 
 
Corrected description SPS as Social Provisions Scale (Section 5.2.3) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
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TABLE OF CONTENTS 
 
 
Schema .......................................................................................................................... 2 
 
1. ABSTRACT ............................................................................................................... 5 
 
2. BACKGROUND/RATIONALE ................................................................................... 5 
 
3. STUDY GOALS/OBJECTIVES ................................................................................. 6 
 
4. Study Population ..................................................................................................... 6 
   4.1 Inclusion Criteria ................................................................................................. 6 
   4.2 Exclusion Criteria ................................................................................................ 7 
 
5.   STUDY DESIGN AND METHODS ............................................................................ 7 
 
6.   STUDY PROCEDURES……………………………………………………………………9 
 
Schedule of Events Table  ................................................................................... 10 
 
7. SAFETY  .................................................................................................................. 11 
 
8. STATISTICAL EVALUATION/CONSIDERATIONS  ............................................... 11 
 
9. DATA COLLECTION AND RECORD KEEPING .................................................... 12 
 
10. REFERENCES ........................................................................................................ 12 
 
11.  APPENDICES 
       Appendix I: Patient Data Collection Instruments/ Surveys 
 
Appendix II: HCCC Data Safety and Monitoring Plan 
 
 
 
 
 

 
 
 
 
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1. Abstract 
Sexual dysfunction is known to affect women newly diagnosed with cancer.  This 
project will evaluate critical elements contributing to sexual dysfunction in women 
who have had surgery for gynecologic cancer and potentially provide a simple, 
easily applicable, and meaningful intervention. The subjects will complete a set of 
questionnaires about health, daily living, sexual activity, and pain before their 
surgery and three times following interventions. Each subject will be randomized to 
receive a perineal application of either lidocaine or a placebo to use immediately 
prior to any sexual encounters for approximately 6 months while maintaining a 
journal of sexual encounters and pain. The subjects and healthcare providers will be 
blinded to the treatment. Total participation will last approximately one year from the 
date of enrollment.  We aim to better characterize elements related to sexual 
dysfunction in this specific population, and provide a treatment intervention to 
improve patient’s quality of life, measured by changes in their physical, 
psychological or social functioning.  
 
2. Background / Rationale 
Sexual dysfunction in gynecologic cancer survivors has been well-documented [1].  
Physical, psychological and social elements contribute to sexual dysfunction in this 
population.  In 2011, over 88,000 women in the United States were diagnosed with 
gynecologic cancers. The majority of these cases affected women over the age of 
60 [2]. Treatment of these cancers, while aimed at preventing death, may cause 
significant changes in physical, psychological or social functioning. These changes 
could lead to negative long-term effects on women’s sexuality. It is important to 
recognize the multifactorial nature of this problem. While research exists regarding 
this topic, few studies include all three domains of sexual functioning. Even fewer 
studies are aimed at designing a specific intervention to address any aspect of the 
dysfunction [1]. One previous study from 1989 at the University of Iowa detailed the 
physical side effects of gynecologic cancer, showing that cancer survivors 
experienced decreased sexual activity, decreased sexual desire, decreased sexual 
excitement, less awareness of signs of orgasm, and dyspareunia compared to 
control groups [3]. In an additional study in the same year by the same group, the 
psychological effects of treatment are detailed. However, these outcomes were not 
directly related to feelings regarding sexual activity or the psychological effects of 
changes in sexuality and were not aimed at interventions [4]. In a study of breast 
cancer survivors, suffering from dyspareunia, Goetsch, et. al., described the use of 
4% lidocaine jelly applied for 3 minutes to areas of pain on a cotton ball. This study 
found that this preparation reduced pain on exam and insertion when compared to 
saline placebo [5]. Lack of a full understanding of physical sexual dysfunction 
following a diagnosis and treatment of gynecologic cancer has been a detriment to 
developing interventions aimed at these issues.   
 

 
 
 
 
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3. Study Goals/Objectives 
 
 
• The primary objective is to identify changes in sexual function assessments 
(Female Sexual Function Index survey, frequency of sexual encounters and a 
visual pain scale assessment with each encounter) after application of an 
aqueous lidocaine solution to the perineum versus a placebo application.   
o Hypothesis: Subjects surgically treated for ovarian, peritoneal, fallopian 
tube, cervical or endometrial cancer will have higher sexual functioning 
and less pain associated with sexual encounters after perineal 
treatment with aqueous lidocaine.    
• 
 Secondary objectives include characterizing the pre and post-treatment 
functioning of gynecologic cancer survivors with respect to physical, 
psychological, and social dimensions. 
o Subjects will complete nine short surveys (The Female Sexual 
Function Index, The PHQ-9, the GAD-7, the SPS, Rosenberg’s Body 
Self-Esteem Index, the Severity of PTS Symptoms Scale, the Adverse 
Childhood Events Index, the SF-12, and the Dyadic Adjustment Scale) 
at their initial visit, assessing physical, psychological, and social 
elements related to sexuality.  The same packet of surveys will be 
completed twelve weeks following surgery, after which, they will be 
randomized to a blinded perineal intervention.  Survey packets will be 
completed 12 and 24 weeks following randomization to the perineal 
intervention. 
o A visual pain scale will be completed after each sexual encounter. 
o A diary documenting frequency of sexual encounters will be collected.  
 
 
 
 
 
4. Study Population 
Subjects comprising this study population include women undergoing initial 
consultation at the University of Iowa Hospitals and Clinics/Holden Comprehensive 
Cancer Center for a documented or suspected diagnosis of ovarian, fallopian tube, 
peritoneal, endometrial or cervical cancer.  Each subject must be scheduled to 
undergo surgical treatment for their disease prior to enrollment.  Enrollment will be 
offered and consent obtained by the Investigator or one of the sub-Investigators at 
the time of initial consultation in the outpatient clinic.   
 
Subjects ultimately diagnosed with one of the previously mentioned gynecologic 
malignancies will remain eligible to continue on the trial, while those found to have 
no evidence of cancer will be excluded.   
 
Inclusion/Exclusion Criteria:  
 
4.1 Inclusion criteria  
• Female 
• Age 18-99 

 
 
 
 
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• Planned to undergo primary surgical treatment at the University of Iowa Hospitals 
and Clinics for a suspected or proven diagnosis of ovarian, fallopian tube, 
peritoneal, endometrial, or cervical cancer 
• Able to give informed consent and follow study procedures 
• No previous reactions to lidocaine applications 
• GOG Performance Status of 0 or 1   
• Reports having engaged in vaginal intercourse at least once in the last 12 
months 
 
 
 
4.2 Exclusion criteria:  
• Failure to confirm invasive ovarian, fallopian tube, peritoneal, endometrial or 
cervical cancer by pathology from primary biopsy or surgery (subjects will not be 
eligible to continue the trial beyond the initial completion of the questionnaires) 
• Diagnosis of another malignancy within the past five years, excluding basal cell 
carcinoma of the skin 
• Patients undergoing primary or adjuvant external pelvic radiation (excluding 
adjuvant vaginal brachytherapy) 
• Previous reactions to lidocaine applications 
• Sexual partners’ previous reactions to lidocaine applications 
  
 
 
 
5. Study Design and Methods 
 
5.1 Data Acquisition 
 
Study data will primarily be obtained through questionnaires and self-reported data 
from a visual pain scale and a diary documenting frequency of sexual encounters.   
 
5.1.1:  The questionnaire packet consists of nine short surveys that capture 
 
information on psychological, social and physical elements previously cited as  
 
 
potential influences on sexual dysfunction.  This survey packet will be completed   
 
prior to a surgical intervention with the intent to capture a “baseline” for the  
 
 
subject.  Completion of the survey packet will be requested at the three month  
 
 
postoperative check-up visit and then at two more sequential three month follow-  
 
up visits.  The perineal intervention will be introduced at the first three month  
 
 
postoperative visit. 
 
 
 
5.1.2:  Subjects will self-report potential discomfort related to each sexual 
 
encounter on a visual pain scale.  These scales will be collected at each three  
 
 
month follow-up visit. 
 
 
5.1.3:  Subjects will be asked to maintain a diary/calendar documenting the 
  
frequency of  sexual encounters and the successful or unsuccessful ability to  
 

 
 
 
 
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apply the perineal intervention.  The diary/calendar will be collected at each three 
 
month visit. 
 
5.2 Procedures 
 
5.2.1: Primary surgical intervention 
Subjects will be eligible and plan to undergo a primary surgical procedure  for the 
treatment of their gynecologic cancer (ovarian, fallopian tube, peritoneal, 
endometrial or cervical) under one of the UIHC gynecologic oncologists.  Surgical 
treatment of these cancers, which includes removing some or all of the 
gynecologic organs, may cause physical as well as perceived changes in sexual 
function.  Surgical treatment for ovarian, fallopian tube, peritoneal, endometrial, 
and early stage cervical cancers is often the first option of treatment for 
appropriately selected patients and critical to a comprehensive treatment 
approach.  It is the goal to systematically evaluate the changes in sexual function 
prior to and following primary surgery for these subjects.  
 
5.2.2 Randomization 
Patients will be randomized to receive either the lidocaine solution or a placebo 
using permuted block technique based on cancer origin. Patients and 
investigators are blinded to assignment.  Only the Investigational Drug Service 
will maintain the blinded codes. Patient and investigator will be unblinded at the 
conclusion of the study. Patients are randomized 1:1 to each arm. 
 
Randomization will be stratified by pathological category of cancer type.  
Thirty subjects will be randomized within each of three groups: 
1. Ovarian, fallopian tube, primary peritoneal cancer 
2. Endometrial cancer 
3. Cervical cancer 
 
 
5.2.3 Evaluation of sexual dysfunction 
 
The survey packet evaluates physical, psychological, and social elements related 
to sexuality. Each packet will be assembled into a large envelope and handed to 
the subject by the healthcare provider in the UIHC Gynecologic Oncology 
outpatient clinic.  The surveys will be completed by the subject in the clinic (in a 
private area) on the day of the visit and then collected by the research data 
managers. 
 
Each survey packet will contain: 
 
1.  Female Sexual Function Index:  A self-report measure of sexual 
functioning 
  
2.  Patient Health Questionnaire 9 (PHQ-9):  Instrument for screening, 
diagnosing, monitoring, and measuring the severity of depression.   
  

 
 
 
 
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3.  Generalized Anxiety Disorder 7-item scale (GAD-7):  A brief measure for 
assessing generalized anxiety disorder.  
  
4.  Social Provisions Scale (SPS):  Instrument to assess provisions of social 
relationships. 
  
5.  Rosenberg’s Body Self-Esteem Index:  Scale that measures global self-
worth by measuring both positive and negative feelings about the self.  
  
6.  Severity of Posttraumatic Stress Symptoms-Adult:  Assesses the severity 
of posttraumatic stress disorder following a particular event or experience. 
  
7.  Adverse Childhood Events Index:  A scale measuring types of physical, 
verbal, and emotional childhood trauma 
  
8.  SF-12:  A generic measure of health status 
  
9.  Dyadic Adjustment Scale:  A relationship adjustment self-report measure. 
 
5.2.4 Diary of Sexual Encounters 
 
A diary of sexual encounters during the 24 weeks of observation will be kept by 
participating subjects.  On the calendar, subjects will be asked to document date 
of sexual encounter and an accompanying successful or unsuccessful perineal 
application of the intervention.  For each encounter, subjects will also be asked to 
mark a visual pain scale. 
 
5.2.5  Adverse Events 
 
Study participants will be asked if there have been any reactions to the solution 
supplied for perineal application at each clinic visit.  They will be encouraged to 
contact their primary gynecologic oncologist or the study chair immediately 
should any adverse reactions be experienced with the perineal application. 
 
Each questionnaire packet will be reviewed immediately following collection for 
an immediate assessment to positive responses to the depression and suicidal 
ideation items of the PHQ-9.  If the PHQ-9 score reflects severe depression, the 
clinician overseeing the patient’s care for their gynecologic malignancy will be 
notified and asked to use their clinical discretion for intervention and appropriate 
referrals within the UIHC health system. 
 
6. Study Procedures 
 
6.1 Self-reported measures of physical, psychological and social stressors 
influencing sexual function  
 
Patient-completed surveys, measuring the different elements of sexual dysfunction, 
will be completed at their initial visit, following their assessment by a UIHC 

 
 
 
 
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gynecologic oncologist, and their decision to pursue a surgical intervention for their 
gynecologic cancer.   At the twelve week postoperative visit, and if a pathologic 
diagnosis of cancer is confirmed, subjects will be asked to complete the same 
survey packet.  At subsequent 3 and 6 month follow-up visits, subjects will be asked 
to complete the survey packet following the visit with their gynecologic oncology 
healthcare provider. 
 
6.2  Aqueous Lidocaine and Placebo Perineal Application 
 
Once subjects have a confirmed diagnosis of their gynecologic cancer, and they 
complete the survey packet at their 12-week follow-up visit, they will be randomized 
to receive a solution containing either aqueous lidocaine or a placebo.  They will also 
be given a package of cotton balls with instructions to put the solution on three 
cotton balls and apply them to the perineum/vaginal introitus for one minute prior to 
sexual intercourse.  Subjects will be asked to document in their diary successful or 
unsuccessful application of the perineal solution.  They will also be asked to 
complete a visual pain scale for each sexual encounter. Subjects will be reminded to 
bring the calendars to the return visit with a phone call. 
 
The aqueous lidocaine/placebo solution will be supplied by the Investigational Drug 
Service. It will be labeled in a manner that does not identify the presence of active 
ingredient.  
 
CALENDAR/SCHEDULE OF EVENTS 
   
 
 
 
Visit 1     
Pre-surgery 
 
 
 
Visit 2      
(12 weeks 
post-
surgery) 
 
 
Visit 3        
(24 weeks 
post-surgery) 
 
 
 
Visit 4        
(32 weeks 
post-surgery)   
 
 
 
Procedures 
 
Informed Consent 
 
x 
 
 
 
 
 
 
 
Inclusion / 
Exclusion Criteria 
 
x 
 
 
 
 
 
 
 
Performance 
Status 
 
x 
 
x 
 
x 
 
x 
 
Physical Exam 
 
x 
 
x 
 
x 
 
x 
 
Questionnaires 
 
x 
 
x 
 
x 
 
x 
Calendar 
Diary of Sexual 
encounters and 
lidocaine/placebo 
usage 
 
x 
x 
 
x 
 
x 
 
 
 
 
 
Randomization 
 
 
x 
 
 
 
 
 
 
 
 

 
 
 
 
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 7. Safety 
 
 
 
7.1  Possible Adverse events of lidocaine include:  
 
• Rare allergic reactions:  Itching; hives; edema of the face or hands; tingling in 
the mouth or throat or chest tightness (which can cause trouble breathing). 
• Other uncommon reactions:  Blurred or double vision; confusion; dizziness; 
lightheadedness; or drowsiness; chest pain or an uneven heartbeat; skin rash; 
swelling in the area where this medicine is applied; and trembling (shaking). 
 
7.2 Other risks of the study procedures include:  
 
• Embarrassment:  discomfort answering some of the questions of the surveys 
(subjects may skip any questions they choose). 
 
7.3  Stopping Rules: 
 
• Subject may stop participating at any time 
• Subject not following instructions  
• Gel becomes unavailable 
• Attending physician decision to withdraw subject 
• Breach of confidentiality 
 
8. Statistical Evaluation/Considerations 
 
The primary objective of this double-blinded, randomized, placebo-controlled study 
is to assess the relative efficacy of aqueous lidocaine solution in improving sexual 
functioning within the population of females undergoing a primary surgical procedure 
for the treatment of ovarian, endometrial, and cervical cancer. Sexual functioning will 
be assessed using the self-reported Female Sexual Function Index (FSFI; full scale 
score ranges from 2 to 36 where scores <26 are indicative of sexual dysfunction). 
Given the lack of existing literature pertaining to sexual functioning immediately 
following surgical intervention, this will be a pilot study aimed at obtaining estimates 
of relative efficacy as well as assessing feasibility. Existing literature on sexual 
functioning in gynecologic cancer survivors, assessed a year or more post-surgery, 
provide median and mean estimates ranging between 16.6-17.2 and 19.75-19.9 (SD 
7.0-9.8), respectively, on the FSFI full scale [6, 7, 8, 9]. We anticipate sexual 
functioning will be even lower in the 24 weeks immediately following surgery. A 
sample size of 15 patients per treatment group achieves 80% power to detect an 
increase of 9.3 between the null hypothesis that both group means are 17.0 and the 
alternative hypothesis that the mean of the aqueous lidocaine solution treatment 
group is 26.3 with estimated group standard deviations of 10.0 and a significance 
level of 0.05. Power calculations were based on using a one-sided two-sample t-test 
for a single point in time while assuming the actual distribution of the FSFI full scale 
is normal. Accordingly, 30 patients from each cancer type—ovarian, endometrial, 
and cervical—will be recruited for a total of 90 subjects. 
 

 
 
 
 
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To assess changes in sexual, physical, psychological, and social domains, linear 
mixed effects regressions models will be utilized. Random effects will be employed 
to account for the longitudinally correlated nature of repeated questionnaire 
measurements.  
 
9. Data Collection and Record Keeping  
 
9.1 Data will be collected primarily by paper forms that include reported information 
from each study participant. Information will be transferred to electronic database 
collection documents for use by the statisticians without any identifiable information.  
 
9.2 In order to protect confidentiality the subject will be assigned an identification 
number. This number will be used on all specimens from the subject and will be 
used for documentation purposes. Data management for the entry, processing, 
storage, and retrieval for this protocol's data will be managed by the principal 
investigator. The database will be located on a computer or in a locked cabinet in a 
locked office. This computer will be secured using UIHC standard protections and 
accessible only by the research team. For quality control, auditing, and data 
integrity, there will be a regular review of data performed periodically throughout the 
data collection phase. 
 
9.3 Study data will be maintained according to University of Iowa policies. Since this 
project includes protected health information, copies of all research records will be 
stored for at least six years following study closure. Study documents will be stored 
in a secure storage room of the department for the required amount of time. The 
space is only accessible to relevant study staff.  
 
 
10. References  
[1] Abbott-Anderson K, Kwekkeboom KL. A systematic review of sexual concerns 
reported by gynecological cancer survivors. Gynecol Oncol. 2012 Mar; 124(3):477-89. 
 
[2] U.S. Cancer Statistics Working Group. United States Cancer Statistics: 1999–2011 
Incidence and Mortality Web-based Report. Atlanta: U.S. Department of Health and 
Human Services, Centers for Disease Control and Prevention and National Cancer 
Institute; 2014. Available at: www.cdc.gov/uscs. 
 
[3] Anderson BL, Anderson B, deProsse C. Controlled prospective longitudinal study of 
women with cancer: I. Sexual functioning outcomes. J Consult Clin Psychol. 1989 
Dec;57(6):683-91. 
 
[4] Anderson BL, Anderson B, deProsse C. Controlled prospective longitudinal study of 
women with cancer: II. Psychological outcomes. J Consult Clin Psychol. 1989 
Dec;57(6):692-7. 
 
[5] Goetsch MF, Lim JY, Caughey AB. Locating pain in breast cancer survivors 
experiencing dyspareunia: A randomized controlled trial. Obstetrics and Gynecology. 
2014 Jun;123(6):1231-1236. 

 
 
 
 
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[6]  Serati M, Salvatore S, Uccella S, Laterza RM, Cromi A, Ghezzi F, Bollis P.  Sexual 
function after radical hysterectomy for early-stage cervical cancer:  is there a difference 
between laparoscopy and laparotomy?  J Sex Med.  2009 Sep; 6(9):2516-22. 
 
[7]  Onujiogu N, Johnson T, Seo S, Mijal K, Rash J, Seaborne L, Rose S, Kushner DM.  
Survivors of endometrial cancer:  who is at risk for sexual dysfunction?  Gynecol Oncol.  
2011 Nov;123(2):356-9. 
 
[8]  Carter J, Chi DS, Brown CL, Abu-Rustum NR, Sonoda Y, Aghajanian C, Levine DA, 
Baser RE, Raviv L, Barakat RR.  Int J Gynecol Cancer.  Cancer-related infertility in 
survivorship.  2010 Jan;20(1):2-8. 
 
[9]  Kim SI, Lee Y, Lim MC, Joo J, Park K, Lee DO, Park SY. Quality of life and sexuality 
comparison between sexually active ovarian cancer survivors and healthy women.  J. 
Gynecol Oncol 2015 Apr;26(2):148-54.