Endoxifen for Breast Cancer

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

32 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Endoxifen Hydrochloride for breast cancer?

Endoxifen, the active form of tamoxifen, has been shown to be safe and well-tolerated in humans, achieving effective levels in the body. It may offer more consistent benefits than tamoxifen due to its reliable absorption and effectiveness in inhibiting breast tumor growth in studies. ^{1 2 3 4 5}

Is Endoxifen safe for humans?

Endoxifen has been shown to be safe and well-tolerated in humans when given in single oral doses, according to a study on healthy subjects. ^{1 6 7 8 9}

How is the drug Endoxifen different from other breast cancer treatments?

Endoxifen is unique because it is the active form of tamoxifen, a common breast cancer drug, and is directly administered, bypassing the need for conversion in the body, which can vary due to genetic differences. This direct administration ensures more consistent and effective treatment outcomes compared to tamoxifen, which requires conversion by the liver enzyme CYP2D6. ^{1 5 7 10 11}

What is the purpose of this trial?

This randomized phase I trial studies the side effects and best dose of endoxifen hydrochloride in treating participants who are undergoing breast surgery. Endoxifen hydrochloride may treat or reduce the risk of breast cancer.

Research Team

Seema A. Khan, M.D.

Principal Investigator

Northwestern University

Eligibility Criteria

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

I have not had breast cancer treatment in the last 2 years, except for radiation on the opposite side.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Endoxifen, a new cornerstone of breast cancer therapy: demonstration of safety, tolerability, and systemic bioavailability in healthy human subjects. [2017]

2. United States pubmed.ncbi.nlm.nih.gov

Pure antiestrogens as a new therapy for breast cancer. [2013]

3. United States pubmed.ncbi.nlm.nih.gov

Risks and benefits of tamoxifen therapy. [2013]

4. United States pubmed.ncbi.nlm.nih.gov

Role of tamoxifen in the long-term treatment and prevention of breast cancer. [2013]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Orally administered endoxifen is a new therapeutic agent for breast cancer. [2017]

6. Korea (South) pubmed.ncbi.nlm.nih.gov

Estimating the risks and benefits of tamoxifen for prophylactic breast cancer chemoprevention in Korea. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Clinical pharmacokinetics and pharmacogenetics of tamoxifen and endoxifen. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Patient reluctance toward tamoxifen use for breast cancer primary prevention. [2022]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Economic evaluation of using a genetic test to direct breast cancer chemoprevention in white women with a previous breast biopsy. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Endoxifen, an Estrogen Receptor Targeted Therapy: From Bench to Bedside. [2022]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Tamoxifen ("Nolvadex"): a review. [2019]