Z-Endoxifen Hydrochloride in Treating Patients With Metastatic or Locally Recurrent Estrogen Receptor-Positive Breast Cancer
This phase I trial is studying the side effects and the best dose of Z-endoxifen hydrochloride in treating patients with metastatic or locally recurrent estrogen receptor-positive (ER+) breast cancer. 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.
Estrogen Receptor-positive Breast Cancer
Recurrent Breast Cancer
Stage IIIC Breast Cancer
Stage IV Breast Cancer
Drug: Z-endoxifen hydrochloride
Other: pharmacogenomic studies
Other: pharmacological study
Other: questionnaire administration
Other: laboratory biomarker analysis
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Study of Z-Endoxifen as a Hormonal Therapy for Breast Cancer|
- MTD defined as the highest dose level where at most 1 of 6 patients develops a dose limiting toxicity and 2 or more of the 3-6 patients treated at the next higher dose level develop a dose limiting toxicity using CTCAE version 4.0 [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
- Progression-free survival (PFS) [ Time Frame: From study entry to the documentation of disease progression, assessed up to 30 days ] [ Designated as safety issue: No ]
- Overall survival (OS) [ Time Frame: From study entry to death due to any cause, assessed up to 30 days ] [ Designated as safety issue: No ]
- Change in hot flash scores [ Time Frame: Baseline to 28 days ] [ Designated as safety issue: No ]
|Study Start Date:||March 2011|
|Estimated Primary Completion Date:||January 2015 (Final data collection date for primary outcome measure)|
Experimental: Treatment (Z-endoxifen hydrochloride)
Patients receive Z-endoxifen hydrochloride PO on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: Z-endoxifen hydrochloride
Other Names:Other: pharmacogenomic studies
Other Name: Pharmacogenomic StudyOther: pharmacological study
Correlative studiesOther: questionnaire administration
Ancillary studiesOther: laboratory biomarker analysis
l. To determine either the maximum-tolerated dose (MTD) of Z-endoxifen hydrochloride or the dose level associated with endoxifen Css of at least 2 uM in women with metastatic estrogen-receptor positive (ER+) breast cancer.
II. To describe the safety profile of Z-endoxifen hydrochloride at each of the doses examined.
III. To evaluate changes in vision after 2 courses of treatment. IV. To gather preliminary data on the clinical benefit in terms of tumor response rate and progression-free survival.
V. To explore changes in the uterine lining thickness after 2 courses of treatment (approximately 56 days) in post-menopausal women (Expansion cohort).
VI. To evaluate the changes in the frequency and severity of hot flashes after 2 courses of treatment (Expansion cohort).
VII. Evaluate changes in irritability scale using a validated Irritability questionnaire (Expansion cohort).
VIII. To evaluate changes in markers of bone formation and absorption after 2 cycles of treatment (Expansion cohort).
IX. To further characterize the safety profile of Z-endoxifen hydrochloride (Expansion cohort).
I. To characterize the plasma pharmacokinetics and urinary excretion of Z-endoxifen hydrochloride 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, progesterone receptor (PR), steroid receptor co-activator (SRC)1, SRC3, as well as the insulin-like growth factor receptor (IGF)1R/PI3K/AKT/mammalian target of rapamycin (mTOR) pathway and Ki67 after 1 cycle of treatment (approximately 28 days).
OUTLINE: This is a multicenter, 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. Blood and urine samples are collected at baseline and periodically during study for pharmacokinetics, pharmacogenetics, and biomarker studies. Patients in the expansion cohort also undergo tumor tissue sample collection for correlative studies. Patients may complete a diary on the frequency and severity of hot flashes at baseline and on day 28 of course 1. They may also complete an irritability questionnaire at baseline and periodically during study.
After completion of study therapy, patients are followed up for 30 days.
|United States, Arizona|
|Mayo Clinic in Arizona||Recruiting|
|Scottsdale, Arizona, United States, 85259|
|Contact: Donald W. Northfelt 507-538-7623 Northfelt.Donald@mayo.edu|
|Principal Investigator: Donald W. Northfelt|
|United States, Florida|
|Mayo Clinic in Florida||Recruiting|
|Jacksonville, Florida, United States, 32224-9980|
|Contact: Michael E. Menefee 507-538-7623 email@example.com|
|Principal Investigator: Michael E. Menefee|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Contact: Matthew P. Goetz 507-284-2511 firstname.lastname@example.org|
|Principal Investigator: Matthew P. Goetz|
|Principal Investigator:||Matthew Goetz||Mayo Clinic|