NCT02311933|Active Not RecruitingPhase 2Results

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

National Cancer Institute (NCI)ClinicalTrials.gov

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3 other identifiers

NCI-2014-02409A011203U10CA180821

Study Type

interventional

Target

Locations

1 country

Sites

561

Timeline

RegisteredDec 2014

StartedMay 2015

CompletionFeb 2027

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.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at P50-P75 for phase_2

Timeline

9mo left

Started May 2015

Longer than P75 for phase_2

Geographic Reach

1 country

561 active sites

Status

active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

11.7 years study duration

Study Progress94%

May 2015Feb 2027

First Submitted

Initial submission to the registry

December 8, 2014

Completed

1 day until next milestone

First Posted

Study publicly available on registry

December 9, 2014

Completed

6 months until next milestone

Study Start

First participant enrolled

May 28, 2015

Completed

5.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 6, 2020

Completed

11 months until next milestone

Results Posted

Study results publicly available

September 28, 2021

Completed

5.4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

February 2, 2027

Expected

Last Updated

May 1, 2026

Status Verified

February 1, 2026

Enrollment Period

5.4 years

First QC Date

December 8, 2014

Results QC Date

September 1, 2021

Last Update Submit

April 30, 2026

Conditions

Recurrent Breast Carcinoma Stage IIIB Breast Cancer AJCC v7 Stage IIIC Breast Cancer AJCC v7 Stage III Breast Cancer AJCC v7 Stage IIIA Breast Cancer AJCC v7 Stage IV Breast Cancer AJCC v6 and v7

Outcome Measures

Primary Outcomes (1)

Progression Free Survival (PFS)
The primary endpoint is progression-free survival (PFS) defined as the time from randomization to documentation of local, regional or distant disease progression or death without progression of disease.
Assessed up to 5 years

Secondary Outcomes (3)

Incidence of Adverse Events, Per Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
Up to 5 years
Tumor Response Rate by Study Arm, Defined as the Number of Patients With a Complete or Partial Response
Up to 5 years
Overall Survival Distribution by Study Arm
The time from registration to death due to any cause, assessed up to 5 years

Other Outcomes (7)

Deoxyribonucleic Acid (DNA) Alterations as Measured by Foundation Medicine
Baseline
Nuclear Receptor Coactivator 3 (SRC3) Immunohistochemistry Expression Levels
Baseline
Change in Biochemical Markers of Bone Turnover
Baseline to week 8 (after course 2)
+4 more other outcomes

Study Arms (2)

Arm I (z-endoxifen hydrochloride)

EXPERIMENTAL

Patients receive z-endoxifen hydrochloride PO on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Drug: Endoxifen HydrochlorideOther: Laboratory Biomarker AnalysisOther: Pharmacological Study

Arm II (tamoxifen citrate)

EXPERIMENTAL

Patients receive tamoxifen citrate PO 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.

Other: Laboratory Biomarker AnalysisOther: Pharmacological StudyDrug: Tamoxifen Citrate

Interventions

Laboratory Biomarker AnalysisOTHER

Correlative studies

Arm I (z-endoxifen hydrochloride)Arm II (tamoxifen citrate)

Pharmacological StudyOTHER

Correlative studies

Arm I (z-endoxifen hydrochloride)Arm II (tamoxifen citrate)

Endoxifen HydrochlorideDRUG

Given PO

Also known as: Z-Endoxifen HCl, Z-Endoxifen Hydrochloride

Arm I (z-endoxifen hydrochloride)

Tamoxifen CitrateDRUG

Given PO

Also known as: Apo-Tamox, Clonoxifen, Dignotamoxi, Ebefen, Emblon, Estroxyn, Fentamox, Gen-Tamoxifen, Genox, ICI 46,474, ICI 46474, ICI-46474, ICI46474, Jenoxifen, Kessar, Ledertam, Lesporene, Nolgen, Noltam, Nolvadex, Nolvadex-D, Nourytam, Novo-Tamoxifen, Novofen, Noxitem, Oestrifen, Oncotam, PMS-Tamoxifen, Soltamox, TAM, Tamax, Tamaxin, Tamifen, Tamizam, Tamofen, Tamoxasta, Tamoxifeni Citras, Zemide

Arm II (tamoxifen citrate)

Eligibility Criteria

Age18 Years+

Sexfemale

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

PRE-REGISTRATION ELIGIBILITY CRITERIA
Women who agree to undergo a standard of care core biopsy of recurrent or metastatic breast cancer to confirm the ER+ (\>= 10% nuclear staining) and HER2 negative status
Patient must have been previously treated with an aromatase inhibitor (either letrozole, anastrozole or exemestane) either in the adjuvant or metastatic setting, and have one of the following types of primary or secondary endocrine resistant disease
Primary clinical resistance is defined as one of the following:
Recurrence within the first 2 years of adjuvant endocrine therapy while on aromatase inhibitor therapy
Progression within first 6 months of initiating first-line endocrine therapy (either aromatase inhibitor or fulvestrant containing regimen) for the treatment of metastatic breast cancer
Secondary clinical resistance is defined as one of the following:
Recurrence after year 2 while receiving adjuvant aromatase inhibitor therapy, or within 12 months of completing adjuvant aromatase inhibitor therapy
Progression occurring 6 or more months after initiating the first endocrine therapy for metastatic disease (either fulvestrant or aromatase inhibitor containing regimen)
Patients with a history of measurable disease as defined by RECIST criteria or bone only disease are eligible; Note: those patients with non-measurable disease and bone metastases are eligible
No history of tumors involving spinal cord or heart
No current evidence of visceral crisis or lymphangitic spread
No known brain metastases
Women must be postmenopausal
Postmenopausal status is verified by:
+57 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

National Cancer Institute (NCI)lead

Study Sites (561)

Southern Cancer Center PC-Providence

Mobile, Alabama, 36608, United States

Location

Anchorage Associates in Radiation Medicine

Anchorage, Alaska, 98508, United States

Location

Anchorage Radiation Therapy Center

Anchorage, Alaska, 99504, United States

Location

Alaska Breast Care and Surgery LLC