Tamoxifen Citrate or Z-Endoxifen Hydrochloride in Treating Patients With Locally Advanced or Metastatic, Estrogen Receptor-Positive, HER2-Negative Breast Cancer
A Randomized Phase II Trial of Tamoxifen Versus Z-Endoxifen HCL in Postmenopausal Women With Metastatic Estrogen Receptor Positive, HER2 Negative Breast Cancer
Sponsor: National Cancer Institute (NCI)
A observational or N/A phase clinical study on Recurrent Breast Carcinoma and Stage III Breast Cancer AJCC v7, this trial is ongoing. The trial is conducted by National Cancer Institute (NCI) and has accumulated 70 data snapshots since 2015. Oncology trials at this stage typically focus on safety, tolerability, and early efficacy signals.
Study Description(click to expand)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...
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.
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First recorded
May 2015
Trial started
Per CT.gov start date — pre-dates our first snapshot
Eligibility 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.
Contact Information
- National Cancer Institute (NCI)
For direct contact, visit the study record on ClinicalTrials.gov .