Endoxifen for Breast Cancer

Not currently recruiting at 2 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Tamoxifen, SERMs, SPRMs, others

Disqualifiers: Skin diseases, Thromboembolic disorder, Uterine cancer, others

Compensation: Varies

Number of Visits: 60

Duration: 3-4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dosage and assess the side effects of endoxifen hydrochloride, which may help treat or reduce the risk of breast cancer. Participants will apply a gel form of the treatment to their breast skin for 21-28 days before undergoing breast surgery. Women scheduled for a mastectomy, either for early-stage breast cancer or as a preventive measure due to high risk, may qualify to participate. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, providing participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must stop using other topical medications on the breast skin during the study. You can use body lotion and other non-medicinal topical products more than 4 hours after applying the study gel.

Is there any evidence suggesting that endoxifen hydrochloride is likely to be safe for humans?

Research has shown that endoxifen hydrochloride has been studied for safety in treating breast cancer. Earlier studies found endoxifen to be safe at doses up to 8.0 mg, with patients tolerating it well and no major safety issues reported. Some research even noted its potential to help fight cancer cells.

Since this trial is in its early phase, the main goal is to learn more about endoxifen's safety and the optimal dose. Early studies often test treatments in small groups to check for side effects. So far, evidence suggests endoxifen is safe for patients, but further research is needed to confirm this. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Endoxifen Hydrochloride is unique because it is applied topically as a gel directly to the breast skin. This delivery method is different from traditional oral hormone therapies like tamoxifen, potentially leading to fewer systemic side effects. Researchers are excited about Endoxifen because it allows the active ingredient to be absorbed locally, directly targeting breast tissue, which might enhance its effectiveness and reduce the risk of side effects commonly associated with oral hormone treatments.

What evidence suggests that endoxifen hydrochloride might be an effective treatment for breast cancer?

Research has shown that endoxifen hydrochloride, which participants in this trial may receive, might help treat breast cancer by blocking estrogen, a hormone cancer cells often need to grow. Studies have found that endoxifen can stop cancer cells from growing in lab tests. Additionally, higher levels of endoxifen in the body have been linked to a lower risk of breast cancer returning. This suggests that endoxifen could be a strong option for fighting breast cancer. However, more research is needed to fully understand its effectiveness in people. ^{3 4 6 7 8}

Who Is on the Research Team?

Seema A. Khan, M.D.

Principal Investigator

Northwestern University

Are You a Good Fit for This Trial?

This trial is for women over 18 with confirmed stage 0-III breast cancer or high risk of breast cancer, who are scheduled for mastectomy. They must have normal organ function and agree to use birth control. Excluded are those with recent breast cancer therapy, skin diseases, a history of blood clots or uterine cancer risks, current users of topical medications on the breasts (unless willing to stop), and pregnant or breastfeeding women.

Inclusion Criteria

I can understand and am willing to sign consent to apply a study treatment daily.

I am ready and can have a mastectomy 3 to 4 weeks after starting the study treatment. I may have breast implants.

I am willing to keep my breast skin away from sunlight and tanning beds while on the study medication.

Exclusion Criteria

I have a high risk of uterine cancer or a condition leading to it.

I have had a mastectomy in the past.

I am a woman with a skin condition like psoriasis or eczema.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants apply endoxifen hydrochloride gel or placebo to both breast skin daily for 21-28 days before breast surgery

3-4 weeks

Daily application

Follow-up

Participants are monitored for safety and effectiveness after treatment

60 days

Follow-up assessment at 60 days

What Are the Treatments Tested in This Trial?

Interventions

• Endoxifen Hydrochloride

Trial Overview

The trial is testing Endoxifen Hydrochloride gel applied to the breast versus a placebo in patients awaiting surgery. The aim is to determine the best dose and side effects of this potential treatment that may reduce the risk or treat breast cancer.

How Is the Trial Designed?

Group I: Cohort I (endoxifen hydrochloride) Experimental Treatment 2 Interventions

Participants apply endoxifen hydrochloride gel to both breast skin and keep it untouched over at least 4 hours once daily for 21-28 days before breast surgery.

Group II: Cohort II (placebo) Placebo Group 2 Interventions

Participants apply placebo to both breast skin and keep it untouched over at least 4 hours once daily for 21-28 days before breast surgery.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 43 women at increased risk for breast cancer, only 4.7% chose to take tamoxifen, despite its proven ability to reduce breast cancer incidence by 49%.

The main reason for declining tamoxifen was fear of side effects, such as endometrial cancer and thromboembolic events, indicating that patient perceptions of risk significantly influenced their decision-making, regardless of educational interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient reluctance toward tamoxifen use for breast cancer primary prevention. Port, ER., Montgomery, LL., Heerdt, AS., et al.[2022]

Endoxifen, a potent metabolite of tamoxifen, shows promise as an alternative therapy in breast cancer, but current research primarily focuses on its use in metastatic cases, indicating a need for further studies to establish its therapeutic role.

Pharmacogenetic factors, particularly CYP2D6 genotypes, significantly impact tamoxifen metabolism and clinical outcomes, suggesting that personalized treatment approaches based on genetic testing may be necessary, although evidence for monitoring endoxifen concentrations is still limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical pharmacokinetics and pharmacogenetics of tamoxifen and endoxifen. Sanchez-Spitman, AB., Swen, JJ., Dezentje, VO., et al.[2019]

Tamoxifen has been effectively used for over 30 years in treating various stages of breast cancer, including advanced and early cases, as well as for breast cancer prevention, demonstrating its broad applicability.

It is well-tolerated and effective in both pre- and postmenopausal women, making it the preferred hormonal treatment for patients with estrogen-receptor positive breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tamoxifen ("Nolvadex"): a review. Clemons, M., Danson, S., Howell, A.[2019]

Z-endoxifen, a potent metabolite of tamoxifen, shows promising antitumor activity in patients with various cancers, including endocrine-refractory metastatic breast cancer, and has substantial oral bioavailability.

Unlike tamoxifen, Z-endoxifen appears to have beneficial effects on bone health while causing little to no endometrial proliferation, making it a potentially safer alternative for breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endoxifen, an Estrogen Receptor Targeted Therapy: From Bench to Bedside. Jayaraman, S., Reid, JM., Hawse, JR., et al.[2022]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7864591/

The Development of Endoxifen for Breast Cancer - PMC

However, after 10 years of follow-up, approximately 22% of patients will have experienced a breast cancer recurrence. In the metastatic setting, tamoxifen is ...

2.

esmoopen.com

esmoopen.com/article/S2059-7029(23)00006-6/fulltext

The impact of endoxifen-guided tamoxifen dose reductions ...

Tamoxifen dose was reduced in 20 patients, 17 of whom were assessable for side-effect analyses. A clinically relevant improvement of >6 points ...

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT01327781

Study Details | NCT01327781 | Z-Endoxifen Hydrochloride ...

Hormone therapy using Z-endoxifen hydrochloride may fight breast cancer by blocking the use of estrogen by tumor cells. Detailed Description. PRIMARY ...

4.

cancer.gov

cancer.gov/news-events/cancer-currents-blog/2017/endoxifen-breast-cancer-nci-support

Bringing the Breast Cancer Drug Endoxifen from Bench to ...

Similarly, a separate group of investigators found that endoxifen halted the growth in five of the six breast cancer cell lines in the NCI-60 ...

5.

e-crt.org

e-crt.org/journal/view.php?number=3626

Endoxifen Concentration Is Associated with Recurrence ...

In summary, an endoxifen cutoff (21.00 ng/mL) higher than previously suggested thresholds could be utilized in prognostication of breast cancer ...

6.

asco.org

asco.org/abstracts-presentations/ABSTRACT94863

Endoxifen for breast cancer: Multiple-dose ...

Endoxifen in plasma samples was determined using LC-MS/MS. Results: Endoxifen was found to be safe up to 8.0 mg. At steady state, it displays dose ...

7.

sciencedirect.com

sciencedirect.com/science/article/pii/S0753332223019030

A randomized Phase I pre-operative window trial of ...

At the endoxifen doses and duration used, and the tissue concentration achieved, we observed a non-significant overall reduction of tumor proliferation (Ki67 LI) ...

8.

oncotarget.com

oncotarget.com/article/27887/text/

Phase 1 study of Z-endoxifen in patients with advanced ...

Evidence of antitumor activity and prolonged stable disease are achieved with Z-endoxifen despite prior tamoxifen therapy, supporting further study of Z- ...