REVIVE: Replens Versus Intra-Vaginal Estrogen for the Treatment of Vaginal Dryness on Aromatase Inhibitor Therapy (REVIVE)

This study is investigating whether breast cancer patients who experience vaginal dryness while on anti-estrogen treatment could benefit from either vaginal estrogen or from a vaginal moisturizer called Replens.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer; Estrogen Receptor Positive Breast Cancer
• Intervention / Treatment: Drug: ESTRING; Drug: Replens

Detailed Description

To evaluate Estring versus Replens for treatment of atrophic vaginitis in breast cancer survivors on adjuvant aromatase inhibitor therapy.

PRIMARY OBJECTIVE 1. To compare improvement of atrophic vaginitis signs and symptoms between women on the vaginal estrogen ring and those on Replens vaginal cream. 1.1 Administer a questionnaire at baseline, 4 weeks, 12 weeks, and 24 weeks to all patients which will assess vaginal dryness and vaginal itching. Over six months, we expect that patients who are receiving vaginal estrogen will have more improvement in atrophic vaginitis symptoms as compared to those women on Replens.

SECONDARY OBJECTIVES 2.1 Assess compliance with aromatase inhibitor (AI) therapy in each arm to see whether vaginal estrogen therapy increases AI compliance among women who have atrophic vaginitis. Compliance will be checked by counting pills at clinic visits at 4 weeks, 12 weeks, and 24 weeks during the study treatment period, and then every 6 months for a period of 4.5 additional years, or until completion of aromatase inhibitor therapy. We expect that compliance in the vaginal estrogen arm will be superior to that of the Replens arm.

Women over the age of 18 who have been diagnosed with stage I-III ER+ breast cancer and are currently taking adjuvant AI therapy who also complain of atrophic vaginitis symptoms including vaginal dryness, vaginal itching, frequent urinary tract infections, or dyspareunia are candidates for this study. Women also must be post-menopausal as defined by any of the following: age >55 years, history of bilateral oophorectomy, amenorrhea for 1 year with intact uterus and ovaries, or serum estradiol and FSH concentrations in the post-menopausal range along with either amenorrhea for 6 months or previous hysterectomy.

• Study Type: Interventional
• Enrollment (Estimated): 44
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Houston Methodist Cancer Center; Phone Number: 713-441-0629; Email: ccresearch@houstonmethodist.org
• Study Contact Backup: Name: Polly Niravath, MD; Phone Number: 713-441-0629; Email: ccresearch@houstonmethodist.org

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Houston Methodist Cancer Center
      • Contact: Polly Niravath, MD; Phone Number: 713-441-0629; Email: ccresearch@houstonmethodist.org

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. be female
2. be 18 years of age or older.
3. have stage I-III ER+ breast cancer
4. be post-menopausal as defined by any of the following: age >55 years, history of bilateral oophorectomy, amenorrhea for 1 year with intact uterus and ovaries, or serum estradiol and FSH concentrations in the post-menopausal range along with either amenorrhea for 6 months or previous hysterectomy.
5. currently take adjuvant AI therapy
6. have vaginal dryness, dyspareunia, or ≥3 urinary tract infections per year since starting AI therapy
7. Patients must agree not to use any additional estrogen during the five year study period. However, use of non-estrogen containing lubricants prior to sexual intercourse, or otherwise, is allowed.

Exclusion Criteria:

1. use of any exogenous estrogen within the preceding four weeks
2. current vaginal infection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Estring; ESTRING	Drug: ESTRING; ESTRING (estradiol vaginal ring) is a slightly opaque ring with a whitish core containing a drug reservoir of 2 mg estradiol. Estradiol, silicone polymers and barium sulfate are combined to form the ring. When placed in the vagina, ESTRING releases estradiol, approximately 7.5 mcg per 24 hours, in a consistent stable manner over 90 days. ESTRING has the following dimensions: outer diameter 55 mm; cross-sectional diameter 9 mm; core diameter 2 mm. One ESTRING should be inserted into the upper third of the vaginal vault, to be worn continuously for three months.; Other Names: (estradiol vaginal ring)
Active Comparator: REPLENS; Replens	Drug: Replens; Replens should be applied vaginally, with a supplied applicator, three times each week.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
What is the number of participants that show improvement of symptoms using vaginal estrogen as compared to the control.	To compare improvement of atrophic vaginitis signs and symptoms between women on the vaginal estrogen ring and those on Replens vaginal cream. 1.1 Administer a questionnaire at baseline, 4 weeks, 12 weeks, and 24 weeks to all patients which will assess vaginal dryness and vaginal itching. Over six months, we expect that patients who are receiving vaginal estrogen will have more improvement in atrophic vaginitis symptoms as compared to those women on Replens.	4.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compliance of use of Aromatase Inhibitor to assure safety	Assess compliance with aromatase inhibitor therapy in each arm. Assess sexual health of survivors. Using an ultra-sensitive estrogen assay, investigate the changes in serum estrogen levels in each arm over time. Compare the change in serum estrogen level from baseline to 6 months in the Estring arm vs. Replens arm.	4.5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
EXPLORATORY OBJECTIVE	To evaluate breast cancer recurrence in each arm over a 5 year time period	5 years
Evaluation of vaginal dryness by vaginal pH	Evaluate vaginal dryness by a potentially more objective measure - vaginal pH. We will test vaginal pH at baseline and 6 months using a pH strip and will report the pH on the research record. We expect that women on vaginal estrogen will have lower pH at 6 months, compared to women on Replens.	6 months from baseline

Collaborators and Investigators

• Sponsor: Polly A. Niravath, MD
• Investigators: Principal Investigator: Polly Niravath, MD, Houston Methodist Cancer Center

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): July 1, 2025

Study Registration Dates

• First Submitted: October 8, 2013
• First Submitted That Met QC Criteria: November 7, 2013
• First Posted (Estimated): November 14, 2013

Study Record Updates

• Last Update Posted (Actual): January 30, 2024
• Last Update Submitted That Met QC Criteria: January 26, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: breast cancer; estrogen receptor positive breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Estradiol
• Other Study ID Numbers: REVIVE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No