Z-Endoxifen Hydrochloride in Treating Patients with Metastatic or Locally Recurrent Estrogen Receptor-Positive Breast Cancer

  • Study type:

    Interventional What is this?

    Describes the nature of a clinical study. Types include:

    • Observational study — observes people and measures outcomes without affecting results.
    • Interventional study (clinical trial) — studies new tests, treatments, drugs, surgical procedures or devices.
    • Medical records research — uses historical information collected from medical records of large groups of people to study how diseases progress and which treatments and surgeries work best.
  • Study phase:

    I What is this?

    During the early phases (phases 1 and 2), researchers assess safety, side effects, optimal dosages and risks/benefits. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid. There are also less common very early (phase 0) and later (phase 4) phases. Phase 0 trials are small trials that help researchers decide if a new agent should be tested in a phase 1 trial. Phase 4 trials look at long-term safety and effectiveness, after a new treatment has been approved and is on the market.

Study IDs

  • Site IRB:

    • Scottsdale/Phoenix, Arizona: 10-006934
    • Rochester, Minnesota: 10-006934
  • NCT ID:

    NCT01327781
  • Sponsor Protocol Number:

    MC093C

About this study

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.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.

See eligibility criteria

Inclusion Criteria:

  • 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 times institutional upper limit of normal (IULN)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 2.5 times IULN (< 5 times IULN if liver function test [LFT] elevations due to liver metastases)
  • Creatinine ≤ 1.5 times IULN
  • 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:
      • Any number of prior systematic therapy regimens is allowed
        • NOTE: prior systematic therapy in the adjuvant setting is not required
      • At least one prior hormone containing regimen in the metastatic setting (tamoxifen if pre-menopausal; aromatase inhibitor if post-menopausal)
        • NOTE: exception: patients that fail (defined as the development of metastatic disease while receiving an adjuvant hormone containing regimen of tamoxifen for premenopausal and aromatase inhibitor for postmenopausal) are eligible and not required to receive additional hormonal containing regimens prior to enrollment
      • At least one prior chemotherapy containing regimen in adjuvant and/or metastatic setting
    • For the expansion cohort(s):
      • At least one prior hormone containing regimen in the metastatic setting (tamoxifen if pre-menopausal; aromatase inhibitor if post-menopausal)
        • NOTE: exception: patients that fail (defined as the development of metastatic disease while receiving an adjuvant hormone containing regimen of tamoxifen for premenopausal and aromatase inhibitor for postmenopausal) are eligible and not required to receive additional hormonal containing regimens prior to enrollment
        • NOTE: a prior hormone containing regimen in the adjuvant setting is not required; a hormonal regimen containing everolimus is allowed
      • Either 1 or 2 prior chemotherapy regimens are allowed but not required such that both are in the metastatic setting or one is in the adjuvant setting and one in the metastatic setting (note, an anthracycline and taxane based regimen delivered in the adjuvant setting would be considered one regimen)
  • Willingness to return to Mayo Clinic Rochester, Arizona, or Florida during treatment phase of the trial
  • Dose Escalation cohort only:
    • Mandatory Translational Research Components
      • Willingness to provide biologic specimens (blood and urine)
    • Dose Escalation cohorts beginning at 160 mg/day: Mandatory Translational Research Components
      • Willingness to provide biologic specimens (tissue)
    • Dose Expansion cohort(s):
      • Mandatory Translational Research Components
        • Willingness to provide biologic specimens (blood, tissue and urine)
      • Note: The goals of this study include assessment of the biologic effects on surrogate markers of Z-endoxifen and therefore, are contingent upon availability of the biologic specimens
  • Women of childbearing potential only: negative serum pregnancy test done ≤ 48 hours prior to registration
  • Capable of swallowing 20-mg capsules

Exclusion Criteria:

  • 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
    • Abnormal uterine bleeding ≤ 1 year prior to registration
  • Personal history of coagulopathy
  • Active DVT and/or PE requiring anti-coagulant therapy
    • Patients who are on anti-coagulant therapy for maintenance are eligible as long as the DVT and/or PE was > 12 months prior to enrollment and there is no evidence for active thrombosis (either DVT or PE)
  • Clinically symptomatic cataracts requiring imminent surgery
    • Patients that have cataracts that do not require surgery are eligible
  • Other invasive malignancy that has been diagnosed or has recurred < 2 years prior to registration except non-melanotic skin cancer or carcinoma-in-situ of the cervix
  • Any co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, hypertension, or psychiatric illness/social situations that would limit compliance with study requirements
  • Failure to fully recover from acute, reversible effects of prior chemotherapy regardless of interval since last treatment; EXCEPTION: Neuropathies - if grade 2 neuropathies have been stable for at least 3 months since completion of prior treatment patient is eligible
  • Tumors involving the spinal cord or heart Note: tamoxifen has known estrogenic side-effects; while Z-endoxifen is considered a potent anti-estrogen and is not known to have estrogenic or agonist effects in vitro, the effect of Z-endoxifen in humans is unknown
  • Uncontrolled brain metastases Note: Brain metastases are not permitted on study unless the metastases have been treated by surgery or radiotherapy, and the patient has been neurologically stable and off steroids for ≥ 12 weeks
  • Plans to begin bisphosphonates or denosumab after registration or began a bisphosphonate or denosumab regimen < 90 days before registration Note: Patients on a stable dose of bisphosphonates or denosumab for > 90 days prior to registration are eligible
  • Any of the following:
    • Pregnant women
    • Nursing women
    • Women of childbearing potential who are unwilling to employ adequate contraception
  • Other concurrent chemotherapy or anti HER2 therapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration [FDA]-approved indication and in the context of a research investigation)

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Matthew Goetz, M.D.

Open for enrollment

Cancer Center Clinical Trials Referral Office

855-776-0015

Rochester, Minn.

Mayo Clinic principal investigator

Matthew Goetz, M.D.

Open for enrollment

Cancer Center Clinical Trials Referral Office

855-776-0015