(Z)-Endoxifen for the Treatment of Premenopausal Women With ER+/HER2- Breast Cancer

Conditions

• Breast Neoplasms
• Estrogen-receptor-positive Breast Cancer
• HER2-negative Breast Cancer
• Invasive Breast Cancer

Eligibility Criteria

Sex

FEMALE

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• (Z)-endoxifen — DRUG
  (Z)-endoxifen capsules. Doses of (Z)-endoxifen to be evaluated include 20 mg (two x 10 mg capsules), 40 mg (one 40 mg capsule) and 80 mg (two x 40 mg capsules).
• goserelin — DRUG
  goserelin 3.6 mg subcutaneous implant

Study Details

This open-label research study is studying (Z)-endoxifen as a possible treatment for pre-menopausal women with ER+/HER2- breast cancer. (Z)-endoxifen belongs to a group of drugs called selective estrogen receptor modulators or "SERM", which help block estrogen from attaching to cancer cells. This study has two parts: a pharmacokinetic part and a treatment part. The PK part (how the body processes the drug) will enroll about 18 participants. All participants will take (Z)-endoxifen capsules daily. Twelve participants will be randomly assigned (50/50 chance) to take (Z)-endoxifen alone or (Z)-endoxifen with a monthly injection of goserelin a drug that temporarily stops the ovaries from making estrogen. This part will help determine the best dose of (Z)-endoxifen by measuring the drug levels in the blood and how long the body takes to remove it. The Treatment Cohort has been simplified to a single study arm (Z)-endoxifen + goserelin. Up to 20 participants will be enrolled that have a baseline Ki-67 ≤ 10% and 45 participants will be enrolled that have a baseline Ki-67\>10%. A key goal of the study is to see if (Z)-endoxifen can slow down or stop tumor growth as measured by a reduction in Ki-67 levels. Tumor tissue samples will be taken by breast biopsy after about 4 weeks of treatment to check levels of this biomarker. If the tumor shows signs of response, participants can continue treatment for up to 24 weeks or until they have surgery. Study participation is up to 6 months (24 weeks of treatment) followed by surgery and a one-month follow up visit.

Key Dates

Start date

Feb 14, 2023

Status verified

Oct 2025

Primary completion

Nov 30, 2026

Completion

Apr 30, 2027

Study Design

Enrollment

87 participants (estimated)

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: PK Cohort
  (Z)-endoxifen capsules orally once daily for 4 weeks. Initial (Z)-endoxifen dose evaluated will be 40 mg with an option to evaluate 20 mg or 80 mg. The PK Cohort participants may extend treatment based on Ki-67% at Week 4. If Ki-67 ≤ 10% at Week 4, participant will be offered option to continue on this treatment for up to 6 cycles/Week 24. Each cycle is 28 days. If Ki-67 \> 10% at Week 4, participant will be withdrawn and go on to surgery.
• Experimental: Treatment Cohort - Single Treatment Arm
  (Z)-endoxifen 40mg capsules orally once daily for 4 weeks + goserelin 3.6 mg by subcutaneous implant approximately every 28 days. (Z)-endoxifen 40mg dose based on results of PK Cohort. If Ki-67 ≤ 10% at Week 4, continue on this treatment for up to 6 cycles/Week 24. Each cycle is 28 days. And then go on to surgery within 3 weeks of Cycle 6 day 26. If Ki-67 \> 10% at Week 4, participant will complete early termination assessments.
• Experimental: PK Cohort 80 mg
  (Z)-endoxifen 80 mg capsules orally once daily for 4 weeks. The PK Cohort participants may extend treatment based on Ki-67% at Week 4. If Ki-67 ≤ 10% at Week 4, participant will be offered option to continue on this treatment for up to 6 cycles/Week 24. Each cycle is 28 days. If Ki-67 \> 10% at Week 4, participant will be withdrawn and go on to surgery.
• Experimental: PK Cohort 80 mg + OFS
  (Z)-endoxifen 80 mg capsules orally once daily for 4 weeks + goserelin 3.6 mg by subcutaneous implant approximately every 28 days. The PK Cohort participants may extend treatment based on Ki-67% at Week 4. If Ki-67 ≤ 10% at Week 4, participant will be offered option to continue on this treatment for up to 6 cycles/Week 24. Each cycle is 28 days. If Ki-67 \> 10% at Week 4, participant will be withdrawn and go on to surgery.

Primary Outcome Measure

PK Cohort - (Z)-endoxifen steady-state plasma concentrations [ Time Frame: After 4 weeks of treatment ]

Central Contacts

• Hayley Erickson
  206-486-1872
  [email protected]

Locations (15)

Find similar trials in Phoenix, AZ

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