Estrogen Receptor Positive Breast CancerPhase 2REVIVENCT01984138
REVIVE: Replens Versus Intra-Vaginal Estrogen for the Treatment of Vaginal Dryness on Aromatase Inhibitor Therapy
A Phase 2 study testing ESTRING, Replens and Vagifem in people with Estrogen Receptor Positive Breast Cancer and Breast Cancer, run by Polly A. Niravath, MD at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Estrogen Receptor Positive Breast Cancer, Breast Cancer
- What is being tested?
- ESTRING, Replens and Vagifem
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2013to Jun 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- be female
- be 18 years of age or older.
- have stage I-III ER+ breast cancer
- 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.
- currently take adjuvant AI therapy
- have vaginal dryness, dyspareunia, or ≥3 urinary tract infections per year since starting AI therapy
- 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.
Who cannot join
- use of any exogenous estrogen within the preceding four weeks
- current vaginal infection.
Trial locations and contacts
1 site in 1 country.
United States1 site
Houston Methodist Cancer Center
Houston, Texas, 77030
About this study
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.
Read the 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.
- Being tested
- ESTRING, Replens, Vagifem
- Keywords
- estrogen receptor positive breast cancer, breast cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ESTRINGDrug
Also called (estradiol vaginal ring)
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.
ReplensDrug
Replens should be applied vaginally, with a supplied applicator, three times each week.
VagifemDrug
Also called Vagifem (estradiol vaginal tablet)
VAGIFEM:
Vagifem (estradiol vaginal tablet) is a small, white round, film-coated, bi-convex vaginal insert, which measures 6 mm. Each vaginal insert contains 10 mcg of estradiol, and it is administered via disposable applicator. The insert is placed vaginally using the applicator, and it will dissolve on its own while releasing estradiol into the local tissues
| Study group | Role | What they receive |
|---|---|---|
| Vaginal Estrogen | Experimental | vaginal estrogen with Estring or Vagifem, per the patient's preference Receives: Drug: ESTRING; Drug: Vagifem |
| REPLENS | Active comparator | Replens Receives: Drug: Replens |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 4.5 years
Secondary outcomes (1)
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.
Measured: 4.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Nov 2013 (estimated)
- Study startSep 2013
- Primary completion3 Jun 2025
- Study completionJun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Estrogen Receptor Positive Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Polly A. Niravath, MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Polly A. Niravath, MD, The Methodist Hospital Research Institute
- Investigators
- Polly Niravath, MD, Principal investigator, Houston Methodist Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01984138
- Sponsor's protocol ID
- REVIVE
- Acronym
- REVIVE
- Status last verified
- Jan 2026
- First submitted
- 8 Oct 2013
- Last updated
- 28 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- REVIVE: Replens Versus Intra-Vaginal Estrogen for the Treatment of Vaginal Dryness on Aromatase Inhibitor Therapy
- ClinicalTrials.gov ID
- NCT01984138
- Acronym / sponsor ID
- REVIVE / REVIVE
- Keywords
- estrogen receptor positive breast cancer, breast cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Polly A. Niravath, MDUniversity, hospital or other
- Study start
- Sep 2013
- Primary completion
- 3 Jun 2025 (actual)
- Study completion
- Jun 2026 (estimated)
- First posted
- 14 Nov 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vaginal Estrogen | Experimental | Drug: ESTRING, Drug: Vagifemvaginal estrogen with Estring or Vagifem, per the patient's preference |
| REPLENS | Active comparator | Drug: ReplensReplens |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- be female
- be 18 years of age or older.
- have stage I-III ER+ breast cancer
- 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.
- currently take adjuvant AI therapy
Key exclusion criteria (2 listed)
- use of any exogenous estrogen within the preceding four weeks
- current vaginal infection.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ESTRINGAlso: (estradiol vaginal ring)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. | Drug | Vaginal Estrogen |
| ReplensReplens should be applied vaginally, with a supplied applicator, three times each week. | Drug | REPLENS |
| VagifemAlso: Vagifem (estradiol vaginal tablet)VAGIFEM: Vagifem (estradiol vaginal tablet) is a small, white round, film-coated, bi-convex vaginal insert, which measures 6 mm. Each vaginal insert contains 10 mcg of estradiol, and it is administered via disposable applicator. The insert is placed vaginally using the applicator, and it will dissolve on its own while releasing estradiol into the local tissues | Drug | Vaginal Estrogen |
Primary outcome
What is the number of participants that show improvement of symptoms using vaginal estrogen as compared to the control.
Time frame: 4.5 years
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.
1 secondary outcome
Compliance of use of Aromatase Inhibitor to assure safety
Time frame: 4.5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jan 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Polly Niravath, MD principal investigator
Houston Methodist Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ESTRING, Replens and Vagifem in people with Estrogen Receptor Positive Breast Cancer and Breast Cancer, run by Polly A. Niravath, MD at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 28 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
What is the number of participants that show improvement of symptoms using vaginal estrogen as compared to the control. (time frame: 4.5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jan 2026.