Ignite Creation Date:
2025-12-25 @ 2:59 AM
Ignite Modification Date:
2026-03-05 @ 9:31 AM
Study NCT ID:
NCT02311933
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-11-10
First Post:
2014-12-08
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Tamoxifen Citrate or Z-Endoxifen Hydrochloride in Treating Patients With Locally Advanced or Metastatic, Estrogen Receptor-Positive, HER2-Negative Breast Cancer
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
A Randomized Phase II Trial of Tamoxifen Versus Z-Endoxifen HCL in Postmenopausal Women With Metastatic Estrogen Receptor Positive, HER2 Negative Breast Cancer
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2025-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This randomized phase II trial studies how well tamoxifen citrate works compared with z-endoxifen hydrochloride in treating patients with breast cancer that has spread to nearby tissue or lymph nodes or other parts of the body and has estrogen receptors but not human epidermal growth factor receptor 2 (HER2) receptors on the surface of its cells. Estrogen can cause the growth of tumor cells. Hormone therapy using tamoxifen citrate or z-endoxifen hydrochloride may fight breast cancer by lowering the amount of estrogen the body makes. It is not yet known whether tamoxifen citrate or z-endoxifen hydrochloride is more effective in treating patients with breast cancer.
Detailed Description:
PRIMARY OBJECTIVES:
I. To assess whether progression-free survival with z-endoxifen hydrochloride (HCl) relative to that with tamoxifen (tamoxifen citrate) is prolonged in postmenopausal women with local advanced or metastatic estrogen receptor (ER) positive/Her2 negative breast cancer.
SECONDARY OBJECTIVES:
I. To assess the safety profile of each of these agents in this patient population.
II. To assess whether the tumor response rate (as determined using the Response Evaluation Criteria in Solid Tumors \[RECIST\] criteria) among those randomized to z-endoxifen HCl differs from that among those randomized to tamoxifen.
III. To estimate the median progression-free survival time for those who receive z-endoxifen HCl after disease progression with tamoxifen.
CORRELATIVE SCIENCE OBJECTIVES:
I. To examine whether ER alpha alterations (defined as either ER activating mutations or ER amplification) are associated with longer progression-free survival (PFS) or higher response rates in the z-endoxifen HCl arm compared to the tamoxifen arm.
II. To determine changes in lipid profiles comparing tamoxifen and z-endoxifen HCl.
III. For each treatment, to evaluate changes in markers of bone formation and absorption after 12 weeks (4 cycles) of treatment.
IV. For all patients and by treatment arm, to determine whether progression-free survival differs with respect to the sensitive to endocrine therapy (SET) index.
V. To examine whether deoxyribonucleic acid (DNA) alterations as measured by Foundation medicine in all coding exons of 287 cancer-related genes as well as 78 polymorphisms in 34 absorption, distribution, metabolism, and excretion (ADME)-related genes are associated with longer PFS or higher response rates in the z-endoxifen HCl arm compared to the tamoxifen arm.
VI. To assess whether the molecular characteristics identified in the tumor biopsies are detectable in the circulating tumor cells (CTCs) and/or cell-free DNA (cfDNA).
VII. For each treatment arm: to examine changes in ER expression on CTCs, changes in estrogen receptor (ESR) mutations or amplification in CTCs or CfDNA and explore the impact of these changes on PFS and response rates.
PHARMACOKINETICS AND PHARMACOGENOMICS OBJECTIVES:
I. To further characterize pharmacokinetics, pharmacogenetics and metabolism of z-endoxifen HCl and tamoxifen.
II. To determine the impact of the concentrations of tamoxifen and its metabolites on PFS in the tamoxifen arm.
III. To determine the impact of the concentrations of z-endoxifen HCl and its metabolites on PFS in the endoxifen arm.
V. To determine the impact of genetic variation in the enzymes responsible for tamoxifen and z-endoxifen HCl metabolism.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive z-endoxifen hydrochloride orally (PO) on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive tamoxifen citrate PO once daily (QD) on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression and bone metastases may cross over to Arm I and receive z-endoxifen hydrochloride starting no later than 28 days after documentation of disease progression.
After completion of study treatment, patients are followed up yearly for up to 5 years.
I. To assess whether progression-free survival with z-endoxifen hydrochloride (HCl) relative to that with tamoxifen (tamoxifen citrate) is prolonged in postmenopausal women with local advanced or metastatic estrogen receptor (ER) positive/Her2 negative breast cancer.
SECONDARY OBJECTIVES:
I. To assess the safety profile of each of these agents in this patient population.
II. To assess whether the tumor response rate (as determined using the Response Evaluation Criteria in Solid Tumors \[RECIST\] criteria) among those randomized to z-endoxifen HCl differs from that among those randomized to tamoxifen.
III. To estimate the median progression-free survival time for those who receive z-endoxifen HCl after disease progression with tamoxifen.
CORRELATIVE SCIENCE OBJECTIVES:
I. To examine whether ER alpha alterations (defined as either ER activating mutations or ER amplification) are associated with longer progression-free survival (PFS) or higher response rates in the z-endoxifen HCl arm compared to the tamoxifen arm.
II. To determine changes in lipid profiles comparing tamoxifen and z-endoxifen HCl.
III. For each treatment, to evaluate changes in markers of bone formation and absorption after 12 weeks (4 cycles) of treatment.
IV. For all patients and by treatment arm, to determine whether progression-free survival differs with respect to the sensitive to endocrine therapy (SET) index.
V. To examine whether deoxyribonucleic acid (DNA) alterations as measured by Foundation medicine in all coding exons of 287 cancer-related genes as well as 78 polymorphisms in 34 absorption, distribution, metabolism, and excretion (ADME)-related genes are associated with longer PFS or higher response rates in the z-endoxifen HCl arm compared to the tamoxifen arm.
VI. To assess whether the molecular characteristics identified in the tumor biopsies are detectable in the circulating tumor cells (CTCs) and/or cell-free DNA (cfDNA).
VII. For each treatment arm: to examine changes in ER expression on CTCs, changes in estrogen receptor (ESR) mutations or amplification in CTCs or CfDNA and explore the impact of these changes on PFS and response rates.
PHARMACOKINETICS AND PHARMACOGENOMICS OBJECTIVES:
I. To further characterize pharmacokinetics, pharmacogenetics and metabolism of z-endoxifen HCl and tamoxifen.
II. To determine the impact of the concentrations of tamoxifen and its metabolites on PFS in the tamoxifen arm.
III. To determine the impact of the concentrations of z-endoxifen HCl and its metabolites on PFS in the endoxifen arm.
V. To determine the impact of genetic variation in the enzymes responsible for tamoxifen and z-endoxifen HCl metabolism.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive z-endoxifen hydrochloride orally (PO) on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive tamoxifen citrate PO once daily (QD) on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression and bone metastases may cross over to Arm I and receive z-endoxifen hydrochloride starting no later than 28 days after documentation of disease progression.
After completion of study treatment, patients are followed up yearly for up to 5 years.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: