Trial · NCT02311933

Tamoxifen Citrate or Z-Endoxifen Hydrochloride in Treating Patients With Locally Advanced or Metastatic, Estrogen Receptor-Positive, HER2-Negative Breast Cancer

NCT02311933, Phase 2, Active not recruiting, National Cancer Institute (NCI); results first posted 2021-09-28

3 sourcestrials-2026-11-12-0.5.0

Cite this record

ConductScience Library. Tamoxifen Citrate or Z-Endoxifen Hydrochloride in Treating Patients With Locally Advanced or Metastatic, Estrogen Receptor-Positive, HER2-Negative Breast Cancer. Trials, record NCT02311933. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT02311933

On this page

Trial

As registered on ClinicalTrials.gov, in the graph's capture of the registry.

Title: Tamoxifen Citrate or Z-Endoxifen Hydrochloride in Treating Patients With Locally Advanced or Metastatic, Estrogen Receptor-Positive, HER2-Negative Breast Cancer
NCT number: NCT02311933
Status: Active not recruiting
Phases: Phase 2
Enrollment: 81 participants, actual
Lead sponsor: National Cancer Institute (NCI)
Conditions: Recurrent Breast Carcinoma, Stage III Breast Cancer AJCC v7, Stage IIIA Breast Cancer AJCC v7, Stage IIIB Breast Cancer AJCC v7, Stage IIIC Breast Cancer AJCC v7, Stage IV Breast Cancer AJCC v6 and v7
Interventions: Endoxifen Hydrochloride, Laboratory Biomarker Analysis, Pharmacological Study, Tamoxifen Citrate
First posted: 2014-12-09
Last updated: 2026-10-26
Results first posted: 2021-09-28

Source ClinicalTrials.gov

Registered outcomes11

Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.

List	Outcome	Time frame	Description
Primary	Progression Free Survival (PFS)	Assessed up to 5 years	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.
Secondary	Incidence of Adverse Events, Per Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0	Up to 5 years	For a given adverse event (AE), the proportion of patients on each treatment arm who report developing a grade 2-5 of this AE will be determined.
Secondary	Tumor Response Rate by Study Arm, Defined as the Number of Patients With a Complete or Partial Response	Up to 5 years	Defined by Response Evaluation Criteria in Solid Tumors on 2 consecutive evaluations at least 6 weeks apart, divided by the total number of eligible patients who began study treatment. A 90% binomial confidence interval will be constructed for the true response rate.
Secondary	Overall Survival Distribution by Study Arm	The time from registration to death due to any cause, assessed up to 5 years	The distribution of survival times will be estimated using the method of Kaplan-Meier.
Other	Deoxyribonucleic Acid (DNA) Alterations as Measured by Foundation Medicine	Baseline	Data will be returned as presence or absence of various DNA alterations, along with description of type and location of the alteration. The nature of alterations in each pathway and gene will be described in tabular format. Association of presence or absence of DNA alterations with PFS will be assessed overall, by pathway, and by gene via Cox regression with the goal of evaluating hazard ratio estimates and confidence intervals. Alterations will be considered together as well as by type. Model fit and stability evaluated, and exact methods used if needed. Performed for both arms and within arms.
Other	Nuclear Receptor Coactivator 3 (SRC3) Immunohistochemistry Expression Levels	Baseline	Within each treatment arm, a point and interval estimate of the difference in tumor response rate between those with metastatic SRC3-positive disease and those with metastatic SRC3-negative disease will be constructed using the properties of the binomial distribution. Also, a point and interval estimate of the odds of disease progression among those with metastatic SRC3-positive disease relative to those with metastatic SRC3-negative disease will be ascertained from the parameter estimates of fitting a proportional hazard model to the progression data.
Other	Change in Biochemical Markers of Bone Turnover	Baseline to week 8 (after course 2)	For each of the markers of bone formation, the percent change after 2 courses of treatment from pre-treatment levels will be determined. A two-sided alpha = 0.01 z-test will be used to assess whether the percent change in a given bone absorption biomarkers differs with respect to treatment.
Other	Z-endoxifen Hydrochloride Area Under Curve (AUC)	Baseline, 2-4, and 4-6 hours post-administration day 1 of course 1; baseline day 2 of course 1; pre-administration day 1 of course 3; pre-administration day 1 of course 9	A population PK will be developed using the software program NONMEM, Version 7. The model will be parameterized in terms of AUC (the primary endpoint), as well as clearance and volume of distribution. Criteria for model selection will include the likelihood ratio test, shrinkage estimates, reasonableness of parameter estimates, as well as goodness-of-fit plots. Attempts will be made to identify the covariates that affect drug behavior or those that explain variability in this patient population.
Other	Pharmacokinetic (PK) Data	Baseline, 2-4, and 4-6 hours post-administration day 1 of course 1; baseline day 2 of course 1; pre-administration day 1 of course 3; pre-administration day 1 of course 9	Examined in an exploratory and hypothesis-generating fashion. Pharmacokinetic-pharmacodynamic (PD) relationships will be explored for effects of endoxifen on efficacy-related, adverse events or laboratory parameters of clinical interest. Exploratory/graphical analyses will be conducted for PK/PD evaluations and may be followed by model-based analyses. The data may be pooled with data from other/future studies for additional population PK/PD analyses.
Other	Pharmacogenetic Data	Baseline	Examined in an exploratory and hypothesis-generating fashion.

1 to 10 of 11Source ClinicalTrials.gov

See all 11 registered outcomes

Outcomes11

Each outcome the trial posted results for, in ClinicalTrials.gov's words.

Type	Outcome	Time frame	Population	Units	Measured as
PRIMARY	Progression Free Survival (PFS)	Assessed up to 5 years	All patients registered who began protocol treatment and were eligible for assessment were included in this analysis. One patient in Arm I was ineligible, two patients in Arm II were ineligible and one patient in Arm II did not receive treatment.	days	MEDIAN
SECONDARY	Incidence of Adverse Events, Per Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0	Up to 5 years
SECONDARY	Tumor Response Rate by Study Arm, Defined as the Number of Patients With a Complete or Partial Response	Up to 5 years
SECONDARY	Overall Survival Distribution by Study Arm	The time from registration to death due to any cause, assessed up to 5 years
OTHER_PRE_SPECIFIED	Deoxyribonucleic Acid (DNA) Alterations as Measured by Foundation Medicine	Baseline
OTHER_PRE_SPECIFIED	Nuclear Receptor Coactivator 3 (SRC3) Immunohistochemistry Expression Levels	Baseline
OTHER_PRE_SPECIFIED	Change in Biochemical Markers of Bone Turnover	Baseline to week 8 (after course 2)
OTHER_PRE_SPECIFIED	Z-endoxifen Hydrochloride Area Under Curve (AUC)	Baseline, 2-4, and 4-6 hours post-administration day 1 of course 1; baseline day 2 of course 1; pre-administration day 1 of course 3; pre-administration day 1 of course 9
OTHER_PRE_SPECIFIED	Pharmacokinetic (PK) Data	Baseline, 2-4, and 4-6 hours post-administration day 1 of course 1; baseline day 2 of course 1; pre-administration day 1 of course 3; pre-administration day 1 of course 9
OTHER_PRE_SPECIFIED	Pharmacogenetic Data	Baseline

1 to 10 of 11Source ClinicalTrials.gov

See all 11 outcomes

Results by group2

Each measurement the trial posted, group by group, in the words and numbers it posted.

Outcome	Group	Category	Value	Spread	Units
Progression Free Survival (PFS)	Arm I (Z-endoxifen Hydrochloride)		130	95% Confidence Interval 76 to 138	days
Progression Free Survival (PFS)	Arm II (Tamoxifen Citrate)		42	95% Confidence Interval 24 to 129	days

Source ClinicalTrials.gov

Participant flow6

How many started, completed or left each group, period by period.

Period	Milestone	Group	Participants
Overall Study	STARTED	Arm I (Z-endoxifen Hydrochloride)	41
Overall Study	STARTED	Arm II (Tamoxifen Citrate)	40
Overall Study	COMPLETED	Arm I (Z-endoxifen Hydrochloride)	41
Overall Study	COMPLETED	Arm II (Tamoxifen Citrate)	40
Overall Study	NOT COMPLETED	Arm I (Z-endoxifen Hydrochloride)	0
Overall Study	NOT COMPLETED	Arm II (Tamoxifen Citrate)	0

Source ClinicalTrials.gov

Adverse events292

Each adverse event the trial posted, group by group: the participants affected out of those at risk.

Type	Event	Organ system	Group	Affected	At risk	Events
other	Anemia	Blood and lymphatic system disorders	Arm I (Z-endoxifen Hydrochloride)	5	41	6
other	Anemia	Blood and lymphatic system disorders	Arm II (Tamoxifen Citrate)	4	39	20
other	Blood and lymph sys disorders - Oth Spec	Blood and lymphatic system disorders	Arm I (Z-endoxifen Hydrochloride)	0	41	0
other	Blood and lymph sys disorders - Oth Spec	Blood and lymphatic system disorders	Arm II (Tamoxifen Citrate)	1	39	4
other	Atrial fibrillation	Cardiac disorders	Arm I (Z-endoxifen Hydrochloride)	0	41	0
other	Atrial fibrillation	Cardiac disorders	Arm II (Tamoxifen Citrate)	1	39	2
other	Sinus bradycardia	Cardiac disorders	Arm I (Z-endoxifen Hydrochloride)	1	41	1
other	Sinus bradycardia	Cardiac disorders	Arm II (Tamoxifen Citrate)	1	39	1
other	Sinus tachycardia	Cardiac disorders	Arm I (Z-endoxifen Hydrochloride)	0	41	0
other	Sinus tachycardia	Cardiac disorders	Arm II (Tamoxifen Citrate)	1	39	2

1 to 10 of 292Source ClinicalTrials.gov

See all 292 adverse events

Adverse event totals6

The totals the trial posted for each group.

Total	Group	Affected	At risk
Total, all-cause mortality	Arm I (Z-endoxifen Hydrochloride)	1	41
Total, all-cause mortality	Arm II (Tamoxifen Citrate)	0	39
Total, other adverse events	Arm I (Z-endoxifen Hydrochloride)	34	41
Total, other adverse events	Arm II (Tamoxifen Citrate)	36	39
Total, serious adverse events	Arm I (Z-endoxifen Hydrochloride)	8	41
Total, serious adverse events	Arm II (Tamoxifen Citrate)	11	39

Source ClinicalTrials.gov

Papers0

The papers the trial lists on ClinicalTrials.gov.

None in this release.

Grants1

The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.

Project	Title	Principal investigators	Organization	Funder	Fiscal years
U10CA180821	Alliance for Clinical Trials in Oncology Operations Center	Galanis, Evanthia; Hahn, Olwen; Kozono, David	ALLIANCE NCTN FOUNDATION	NATIONAL CANCER INSTITUTE	2014 to 2026

Source NIH RePORTER

Trial comparisons2

Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.

Comparison	Source
Arm I (Z-endoxifen Hydrochloride) vs Arm II (Tamoxifen Citrate): deaths from any cause	Trial comparisons
Arm I (Z-endoxifen Hydrochloride) vs Arm II (Tamoxifen Citrate): serious adverse events	Trial comparisons

Tests0

The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.

None in this release.

Data dates

The day each source was copied for this release.

ClinicalTrials.gov: 2026-11-12; ClinicalTrials.gov
Results, from AACT: 2026-03-23; AACT
NIH grant links: 2026-11-13; NIH RePORTER

Sources 3

ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
ClinicalTrials.govNo license stated
NIH RePORTER's clinical studies and project filesPublic domain

Each source's terms

ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
ClinicalTrials.govnone stated
NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)

ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.

For software

Read this trial from software.

The record and each of its lists are JSON, twenty rows a page. No key.

GET https://conductscience.org/api/trials/v1/NCT02311933

GET https://conductscience.org/api/trials/v1/NCT02311933/events?page=2

API reference For AI assistants