NCT01327781

Z-Endoxifen Hydrochloride in Treating Patients With Metastatic or Locally Recurrent Estrogen Receptor-Positive Breast Cancer

Phase I Study of Z-Endoxifen as a Hormonal Therapy for Breast Cancer

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 62 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the side effects and the best dose of Z-endoxifen hydrochloride in treating patients with estrogen receptor-positive (ER+) breast cancer that has spread to other places in the body (metastatic) or has come back at or near the same place as the original tumor (locally recurrent). Estrogen can cause the growth of breast cancer cells. Hormone therapy using Z-endoxifen hydrochloride may fight breast cancer by blocking the use of estrogen by tumor cells.

Detailed description

PRIMARY OBJECTIVES: l. To determine either the maximum-tolerated dose (MTD) of Z-endoxifen hydrochloride or the dose level associated with endoxifen steady state concentration (Css) of at least 2 uM in women with metastatic estrogen-receptor positive (ER+) breast cancer. (Dose Escalation Cohort) II. To describe the safety profile of Z-endoxifen (Z-endoxifen hydrochloride) at each of the doses examined. (Dose Escalation Cohort) III. To evaluate changes in vision after 2 cycles of treatment. (Dose Escalation Cohort) IV. To gather preliminary data on the clinical benefit in terms of tumor response rate and progression-free survival. (Dose Escalation Cohort) V. To evaluate the changes in the frequency and severity of hot flashes after 2 cycles of treatment. (Expansion Cohort) VI. Evaluate changes in irritability scale using a validated irritability questionnaire. (Expansion Cohort) VII. To evaluate changes in markers of bone formation and absorption after 2 cycles of treatment. (Expansion Cohort) XIII. To evaluate changes in vision after 2 cycles of treatment. (Expansion Cohort). IX. To further characterize the safety profile of Z-endoxifen. (Expansion Cohort) SECONDARY OBJECTIVES: I. To characterize the plasma pharmacokinetics and urinary excretion of Z-endoxifen at each of the doses examined. II. For patients beginning in dose level 7 as well as the expansion cohorts, we will describe any changes in tumor expression of ER (both full length and truncated forms), progesterone receptor (PR), steroid receptor co-activator (SRC)1, SRC3, as well as the insulin-like growth factor receptor (IGF)1R/phosphatidylinositol 3 kinase (PI3K)/v-akt Murine Thymoma Viral Oncogene Homolog 1 (AKT)/mammalian target of rapamycin (mTOR) pathway and proliferation-related Ki-67 antigen (Ki67) after 1 cycle of treatment (approximately 28 days). III. To determine the frequency of estrogen receptor 1 (ESR1) mutations and the presence of antitumor activity (response rate and progression free survival \[PFS\]) in all patients whose tumors harbor ESR1 alterations. IV. To determine whether the ESR1 mutations identified in pre-treatment tumor biopsies can be detected in matched plasma cell free deoxyribonucleic acid (DNA) from the same patients. OUTLINE: This is a dose-escalation study followed by an expansion cohort study. Patients receive Z-endoxifen hydrochloride orally (PO) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 30 days and then at 3 months.

Conditions

• HER2/Neu Positive
• Recurrent Breast Carcinoma
• Stage IIIC Breast Cancer AJCC v7
• Stage IV Breast Cancer AJCC v6 and v7

Interventions

Type	Name	Description
DRUG	Endoxifen Hydrochloride	Given PO
OTHER	Laboratory Biomarker Analysis	Correlative studies
OTHER	Pharmacological Study	Correlative studies
OTHER	Questionnaire Administration	Ancillary studies

Timeline

• Start date: 2011-03-25
• Primary completion: 2017-03-05
• Completion: 2026-10-30
• First posted: 2011-04-04
• Last updated: 2026-04-13

Locations

3 sites across 1 country: United States