NCT01327781

Brief Summary

This phase I trial studies the side effects and the best dose of Z-endoxifen hydrochloride in treating patients with estrogen receptor-positive (ER+) breast cancer that has spread to other places in the body (metastatic) or has come back at or near the same place as the original tumor (locally recurrent). 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.

Trial Health

75
On Track

Trial Health Score

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

Enrollment
62

participants targeted

Target at P75+ for phase_1

Timeline
6mo left

Started Mar 2011

Longer than P75 for phase_1

Geographic Reach
1 country

3 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

Study Progress97%
Mar 2011Oct 2026

Study Start

First participant enrolled

March 25, 2011

Completed
6 days until next milestone

First Submitted

Initial submission to the registry

March 31, 2011

Completed
4 days until next milestone

First Posted

Study publicly available on registry

April 4, 2011

Completed
5.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 5, 2017

Completed
9.7 years until next milestone

Study Completion

Last participant's last visit for all outcomes

October 30, 2026

Expected
Last Updated

April 13, 2026

Status Verified

February 1, 2026

Enrollment Period

6 years

First QC Date

March 31, 2011

Last Update Submit

April 9, 2026

Conditions

Outcome Measures

Primary Outcomes (1)

  • 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

    Assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. The maximum grade of each type of toxicity will be recorded for each patient. For each toxicity reported by dose level, the percentage of patients developing any degree of that toxicity as well as the percentage of patients developing a severe degree (grade 3 or higher) will be determined.

    28 days

Secondary Outcomes (3)

  • Progression-free survival

    From study entry to the documentation of disease progression, assessed up to 3 months

  • Overall survival

    From study entry to death due to any cause, assessed up to 3 months

  • Change in hot flash scores graded using a hot flash diary and the hot flash interference scale

    Baseline to day 28

Other Outcomes (11)

  • Change in tumor expression levels of SRC3

    Baseline up to day 28

  • Change in tumor expression levels of SRC1

    Baseline up to day 28

  • Change in tumor expression levels of IGF1R

    Baseline up to day 28

  • +8 more other outcomes

Study Arms (1)

Treatment (Z-endoxifen hydrochloride)

EXPERIMENTAL

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: Endoxifen HydrochlorideOther: Laboratory Biomarker AnalysisOther: Pharmacological StudyOther: Questionnaire Administration

Interventions

Given PO

Also known as: Z-Endoxifen HCl, Z-Endoxifen Hydrochloride
Treatment (Z-endoxifen hydrochloride)

Correlative studies

Treatment (Z-endoxifen hydrochloride)

Correlative studies

Treatment (Z-endoxifen hydrochloride)

Ancillary studies

Treatment (Z-endoxifen hydrochloride)

Eligibility Criteria

Age18 Years+
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Histologically confirmed diagnosis of metastatic or locally recurrent breast cancer
  • ER positive defined as \> 1% nuclear staining on the biopsy that was obtained at the confirmation of metastatic or locally recurrent disease
  • Lesion type of either evaluable or measurable disease
  • Pre- or post-menopausal female
  • For the expansion cohorts: tumor that is accessible for biopsy
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
  • Life expectancy \> 16 weeks
  • Capable of understanding investigational nature, potential risks and benefits of the study and able to provide written informed consent
  • Absolute neutrophil count (ANC) \>= 1,000/uL
  • Platelet count \>= 75,000/uL
  • Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional ULN (\< 5 x institutional ULN if liver function test \[LFT\] elevations due to liver metastases)
  • Creatinine =\< 1.5 x institutional ULN
  • Women with human epidermal growth factor (HER)-2 positive disease must have received and progressed on at least one prior anti-HER-2 directed regimen (trastuzumab, lapatinib) for their metastatic disease
  • For dose escalation cohort:
  • +22 more criteria

You may not qualify if:

  • Any of the following therapies prior to registration:
  • Chemotherapy =\< 3 weeks
  • Immunotherapy =\< 3 weeks
  • Biologic therapy =\< 3 weeks
  • Hormonal therapy =\< 3 weeks
  • Monoclonal antibodies =\< 3 weeks
  • Radiation therapy =\< 3 weeks
  • Anti-Her-2 directed therapy =\< 3 weeks
  • Prior endoxifen therapy
  • Prior history of:
  • Stroke =\< 6 months prior to registration
  • Seizures =\< 3 months prior to registration
  • Deep vein thrombosis (DVT) or pulmonary embolism (PE) =\< 12 months prior to registration
  • Two or more episodes of DVT and/or PE =\< 5 years prior to registration
  • Crystalline retinopathy
  • +20 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue Diseases

Study Officials

  • Matthew P Goetz

    Mayo Clinic

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 31, 2011

First Posted

April 4, 2011

Study Start

March 25, 2011

Primary Completion

March 5, 2017

Study Completion (Estimated)

October 30, 2026

Last Updated

April 13, 2026

Record last verified: 2026-02

Locations