Letrozole for Endometriosis Pain Management

(APPOSE Trial)

Overseen By Marcelle I Cedars, MD

Age: 18 - 65

Sex: Female

Trial Phase: Phase 2

Sponsor: University of California, San Francisco

Disqualifiers: Significant disease, illness, psychiatric, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests letrozole, a medication, to determine its effectiveness in managing pain related to endometriosis during ovarian hyperstimulation. Researchers aim to assess letrozole's ability to reduce symptoms, improve egg quality, and increase pregnancy rates. Participants will receive either letrozole or a placebo (a pill with no active medicine) and will complete surveys to track their symptoms. This trial may suit individuals diagnosed with endometriosis who plan to undergo ovarian hyperstimulation and freeze their eggs or embryos. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that letrozole is usually well-tolerated for treating endometriosis. Studies have found that patients using letrozole for up to six months did not experience significant side effects. In another study, none of the participants reported any side effects during their treatment with letrozole. These findings suggest that letrozole is safe for many people when used to manage pain from endometriosis. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for endometriosis?

Letrozole is unique because it offers a different approach to managing endometriosis pain compared to traditional options like hormonal therapies or pain relievers. Most treatments for endometriosis focus on altering hormone levels to reduce symptoms, but letrozole works by inhibiting aromatase, an enzyme involved in estrogen production, which could potentially reduce estrogen levels more effectively. This mechanism might help in managing pain with potentially fewer side effects, making it a promising option for those who haven't found relief with standard treatments. Researchers are excited about letrozole's potential to offer a novel and effective way to alleviate the discomfort associated with endometriosis.

What evidence suggests that letrozole might be an effective treatment for endometriosis?

Research has shown that letrozole, which participants in this trial may receive, can significantly reduce pain caused by endometriosis. Studies have found that individuals using letrozole experience a 50%-70% decrease in pain, providing substantial relief for those with chronic pain. Specifically, one study noted a clear improvement in long-term pelvic pain after six months of letrozole use. Letrozole lowers estrogen levels, which can help shrink endometriosis tissue and reduce pain, making it a promising option for effectively managing endometriosis symptoms. Participants in this trial may also be assigned to a placebo group to compare the effects. ^{5 6 7 8 9}

Who Is on the Research Team?

Marcelle I Cedars

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for women aged 18-42 with a prior diagnosis of endometriosis who are planning to undergo controlled ovarian hyperstimulation and intend to freeze all retrieved eggs or embryos. It's not suitable for those with significant health issues, psychiatric disorders, or hypersensitivity to letrozole.

Inclusion Criteria

I have been diagnosed with endometriosis either through surgery or an ultrasound.

You are planning to undergo a medical procedure called controlled ovarian hyperstimulation.

Planning to freeze all retrieved oocytes/embryos prior to transfer

Exclusion Criteria

Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow-up, or interpretation of study results

You are allergic to letrozole.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Ovarian Stimulation

Participants undergo controlled ovarian hyperstimulation with either letrozole or placebo

2 weeks

Baseline ultrasound, day of trigger shot

Egg Retrieval and Immediate Post-Retrieval

Egg retrieval occurs, and medication is continued for 2 weeks post retrieval

2 weeks

Egg retrieval, follow-up visits for medication continuation

Follow-up

Participants are monitored for endometriosis-related symptoms and other outcomes

12 weeks

Surveys at 3, 6, and 12 weeks post retrieval

What Are the Treatments Tested in This Trial?

Interventions

• Letrozole
• Placebo oral tablet

Trial Overview The study compares the effects of Letrozole versus a placebo on pain during ovarian stimulation in patients with endometriosis. It also examines how Letrozole affects egg/embryo quality and pregnancy rates in a randomized double-blind setup.

How Is the Trial Designed?

Group I: Endometriosis Letrozole Experimental Treatment 1 Intervention

Participants will be asked to take 5mg letrozole daily throughout their ovarian stimulation and for 2 weeks following retrieval. Participants will be blinded to their randomization to letrozole. Participants will be asked to complete surveys during their stimulation and up to 12 weeks following retrieval to evaluate endometriosis associated symptoms. Specifically, surveys will be administered at baseline ultrasound appointment for controlled ovarian hyperstimulation cycle, the day of trigger shot, 3 weeks following egg retrieval, 6 weeks following egg retrieval and 12 weeks following egg retrieval. There will be a total of 20 participants in this arm.

Group II: No Endometriosis Control Active Control 1 Intervention

Participants will be asked to complete surveys during their ovarian stimulation and up to 12 weeks following retrieval to evaluate symptoms of pelvic pain. Specifically, surveys will be administered at baseline ultrasound appointment for controlled ovarian hyperstimulation cycle, the day of trigger shot, 3 weeks following egg retrieval, 6 weeks following egg retrieval and 12 weeks following egg retrieval. There will be a total of 20 participants in this arm.

Group III: Endometriosis Placebo Placebo Group 1 Intervention

Participants will be asked to take one tablet placebo daily throughout their ovarian stimulation and for 2 weeks following retrieval. Participants will be blinded to their randomization to placebo. Participants will be asked to complete surveys during their stimulation and up to 12 weeks following retrieval to evaluate endometriosis associated symptoms. Specifically, surveys will be administered at baseline ultrasound appointment for controlled ovarian hyperstimulation cycle, the day of trigger shot, 3 weeks following egg retrieval, 6 weeks following egg retrieval and 12 weeks following egg retrieval. There will be a total of 20 participants in this arm.

Letrozole is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Femara for:

• Breast cancer in postmenopausal women
• Increasing the chance of ovulation in women with polycystic ovary syndrome

Approved in European Union as Letrozole for:

• Early breast cancer in postmenopausal women
• Advanced breast cancer in postmenopausal women

Approved in Canada as Letrozole for:

• Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer
• First-line treatment of postmenopausal women with hormone receptor-positive advanced breast cancer

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4301232/

Effect of Letrozole on endometriosis-related pelvic pain Conclusion: Both treatment modalities showed comparable effectiveness in the treatment of pains related to endometriosis and in comparison with OCP, Letrozole ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1110569013000691

Efficacy of letrozole in treatment of endometriosis-related ... In the present study there was a significant improvement of chronic pelvic pain observed after 6 months of treatment as mean pain score falls ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11724681/

Management of Endometriosis-Related Pain - PubMed Central A study reported that AIs, such as letrozole and anastrozole, significantly reduce pain scores by 50%-70% in patients with refractory ...

4. cureus.com cureus.com/articles/317076-management-of-endometriosis-related-pain-comparing-the-effectiveness-of-hormonal-therapy-surgical-interventions-and-complementary-therapies

Management of Endometriosis-Related Pain: Comparing ... A study reported that AIs, such as letrozole and anastrozole, significantly reduce pain scores by 50%-70% in patients with refractory ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0015028203028747

Treatment of endometriosis and chronic pelvic pain with ... The combination of letrozole and norethindrone acetate achieved marked reduction of laparoscopically visible and histologically confirmed endometriosis in all ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2014/020726s027lbl.pdf

FEMARA (letrozole) tablets - accessdata.fda.gov The median treatment duration of adjuvant treatment was 60 months and the median duration of follow-up for safety was 73 months for patients receiving Femara ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4921342/

Treatment of Endometriosis and Chronic Pelvic Pain with ... Letrozole is an effective drug for treatment of endometriosis. The drug has not shown any significant side effects during its use for a period of six months.

8. medsafe.govt.nz medsafe.govt.nz/profs/datasheet/l/letroletab.pdf

Data Sheet - Letrole Study D2407 is an open-label, randomized, multicentre post approval safety study designed to compare the effects of adjuvant treatment with letrozole and ...

9. medicalnewstoday.com medicalnewstoday.com/articles/femara

Femara (letrozole): Side effects, off-label infertility use, and ... Femara is sometimes used off-label to help manage pain related to endometriosis in females who haven't experienced the desired results from other treatments.