Breast Carcinoma, Vaginal Atrophy
Conditions
Brief summary
This phase III trial compares the effect of vaginal fractional CO2 laser therapy to placebo for the treatment of vaginal dryness in breast cancer survivors with symptoms of genitourinary syndrome of menopause (GSM). Placebo therapy is an inactive treatment that is designed to mimic as closely as possible the active treatment being studied in a clinical trial. In this trial, patients will not be told whether they will be in the laser treatment group or the placebo group until 6-weeks after the third treatment visit (patient-blinded). At that point, patients who received placebo can elect to receive laser treatment similar to the other group. GSM is group of symptoms that affect the female genital and urinary systems and results from the lack of estrogen. Vaginal dryness can be commonly experienced with normal aging, with menopause, or come about from medications used to treat breast cancer such as chemotherapy or endocrine therapies like tamoxifen or aromatase inhibitors. Vaginal fractional CO2 laser therapy may help reduce vaginal dryness. compared to placebo.
Detailed description
PRIMARY OBJECTIVE: I. To determine whether vaginal fractional carbon dioxide (CO2) laser treatment is superior to vaginal placebo procedure in improving the severity of vaginal dryness, based on an 11-point (0-10) patient reported numerical analog scale. SECONDARY OBJECTIVES: I. To determine whether vaginal fractional CO2 laser treatment is superior to vaginal placebo procedure in improving patient-reported vaginal discomfort during sexual activity, based on the vaginal discomfort domain of the Patient Reported Outcomes Measurement Information System (PROMIS) Sexual Function version (v.) 2.0 Brief Profile-Female. II. To determine whether vaginal fractional CO2 laser therapy results in improvement in patient-reported quality of life, based on a single item 11-point numerical analog scale. III. To evaluate potential toxicities associated with vaginal fractional CO2 laser therapy. OUTLINE: Patients are randomized at a 2:1 ratio to Arm I and Arm II. ARM I: Patients undergo vaginal fractional CO2 laser therapy over 20-30 minutes every 6 weeks for 3 treatments in the absence of disease progression or unacceptable toxicity. ARM II: Patients undergo placebo procedure over 20-30 minutes every 6 weeks for 3 treatments in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 6 weeks, and 3,6, 12, 18 and 24 months after the last procedure visit.
Interventions
DEVICELaser Therapy
Undergo vaginal fractional CO2 laser therapy
DEVICESham Intervention
Undergo placebo procedure
OTHERQuestionnaire Administration
Ancillary studies
OTHERQuality of Life Assessment
Ancillary studies
Sponsors
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
The provider will not be blinded to the arm the patient is on. PRO measures will be administered by research personnel who are blinded to the arm the patient is enrolled on at each study time point.
Eligibility
Sex/Gender
FEMALE
Age
22 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Women with a history of breast cancer who have not had exposure to chemotherapy, targeted therapy, immunotherapy and/or radiation) within 3 months prior to registration. * Breast cancer survivors not currently on therapy are eligible * Patients may be receiving ongoing endocrine therapy These patients must be receiving adjuvant endocrine therapy prior to registration and intend to continue the same endocrine therapy for the 4 months while they are receiving protocol treatment, unless a clinically necessary change is indicated at the discretion of the patient's medical oncologist. \* Patients who are receiving endocrine therapy +/- monoclonal therapy like trastuzumab and pertuzumab are eligible * Patients on targeted therapy such as CD4/6 inhibitors are not eligible. Patients receiving concurrent chemotherapy and immunotherapy are not eligible. * Patient-reported vaginal dryness with or without dyspareunia of at least moderate severity on average, defined as \>= 4 on a 0-10-point scale that has been bothersome for \>= 3 months and for which the patient wants to undergo the study procedure * No prior gynecologic cancer, vaginal intra-epithelial neoplasia, pelvic radiation or pelvic reconstructive surgery utilizing mesh. Patients with cervical intraepithelial neoplasia are eligible * No history of scleroderma, lupus, systemic sclerosis, mixed connective tissue disorder, undifferentiated connective tissue disorder or collagen vascular disease, dermatomyositis, polymyositis, lichen sclerosis or vulvar vestibulitis * No pelvic surgery that involved a vaginal incision within 6 months of registration. Patients who received laparoscopic BSO (Bilateral salpingo-oophorectomy) are eligible * No systemic estrogen or progesterone, vaginal estrogen, vaginal prasterone, ospemifene, and/or androgen therapy within 6 weeks prior to registration * No other suspected contraindications for undergoing laser therapy * No prior vaginal laser therapy at any time. Patients who would have completed any type of vaginal laser resurfacing procedure at any time prior to the start of study treatment are not eligible * No known concurrent invasive carcinoma/malignancy. Patients with carcinoma in situ are eligible. Patients with a prior malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible if not currently receiving treatment * Postmenopausal based on at least one of the following criteria at the time of registration: * Women 50 or older with no spontaneous regular menses \> 12 months * On ovarian suppression (i.e., gonadotrophin releasing hormone \[GNRH\] agonist/antagonist) for at least 6 months or greater, with plans to continue such treatment for at least 18 weeks * Bilateral oophorectomy * Women on aromatase-inhibitor (AI) therapy (i.e., clinically judged to be postmenopausal) * In order to complete the mandatory patient-completed measures, participants must be able to speak, read and understand English or Spanish * Age \>= 22 years * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 * No medical history of: keloid formation, genital fistula, thin recto-vaginal septum (defined as a distance of \< 2 cm between the vaginal opening and the anal opening)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in patient reported vaginal dryness severity | Up to 18 weeks | Will use an 11-point (0-10 scale) numerical analog scale to assess patient reported severity of vaginal dryness. Higher scores represent worse symptoms (0: None - 10: Worst possible). The vaginal dryness scores at each time point will be summarized separately by treatment arm using the mean (standard deviation) and median (range). The score changes from baseline to the 18-week time point (T4) will be compared using two-sample t-test or Wilcoxon rank-sum test as appropriate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in vaginal discomfort during sexual activity (for sexually active subset of study population only) | Baseline up to 24 months after completion of treatment | Assessed using the Vaginal discomfort domain of Patient Reported Outcomes Measurement Information System (PROMIS) Sexual Function version (V) 2.0 Brief Profile - Female (only the sexually active women will be evaluable for this, which is estimated to be approximately 50% of the population). Higher scores represent more discomfort (1: None - 5: A lot). Change in the vaginal discomfort domain of the PROMIS Sexual Function v. 2.0 Brief Profile-Female from baseline to each post-therapy-initiation time point will be summarized by treatment arm and will be compared as described for the primary endpoint. |
| Change in quality of life | Baseline up to 24 months after completion of treatment | Evaluated using 11-point (0-10) numerical analog scale. Higher scores represent better quality of life (0: As bad as it can be - 10: As good as it can be). Change in patient reported quality of life from baseline to each post-therapy initiation time point will be summarized and compared as described for the primary endpoint. |
| Incidence of adverse events associated with vaginal fractional CO2 laser therapy | Up to 24 months after completion of treatment | Incidences of toxicities in the fractional CO2 laser therapy arm will be summarized by type. Common toxicities that occur in both arms will be summarized and compared between arms using the Chi-square test or Fisher's exact test, as appropriate. |
Countries
United States
Contacts
CONTACTMaryam Lustberg, MD, MPH
STUDY_CHAIRMaryam Lustberg, MD, MPH
Yale University Comprehensive Cancer Center
Outcome results
None listed