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

Overview

  • Study type

    Interventional
  • Study phase

    II
  • Study IDs

  • 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.
  • 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.

  • Site IRB
    • Scottsdale/Phoenix, Arizona: 15-002590
    • Jacksonville, Florida: 15-002590
    • Rochester, Minnesota: 15-002590
    NCT ID: NCT02311933
    Sponsor Protocol Number: A011203

About this study

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.

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:

  • 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:
      • Prior bilateral surgical oophorectomy, or
      • Age >= 60 years, or
      • Age < 60 with no menses for > 1 year with follicle-stimulating hormone (FSH) and estradiol levels within post menopausal range, according to institutional standard
  • Prior treatment
    • No more than two prior chemotherapy regimens in the metastatic setting
    • Prior treatment with an aromatase inhibitor (either anastrozole, letrozole or exemestane), either in the adjuvant or metastatic setting is required
    • Unlimited prior endocrine regimens in the metastatic setting, which may have included an everolimus or cyclin dependent kinase (CDK) 4/6 inhibitor (such as palbociclib, abemaciclib or ribociclib) containing regimen
    • Prior tamoxifen treatment is allowed in the adjuvant setting, but patients must not have experienced relapse within 1 year of stopping tamoxifen
    • No prior treatment with tamoxifen in the metastatic setting
    • No prior treatment with endoxifen
    • Patients who have not fully recovered from acute, reversible effects of prior therapy regardless of interval since last treatment are not eligible to participate in this study
      • EXCEPTION: neuropathies-if grade 2 neuropathies have been stable for at least 3 months since completion of prior treatment patient is eligible
  • Not receiving any medications or substances that are strong inhibitors of cytochrome P450 family 2, subfamily D, polypeptide 6 (CYP2D6)
  • Not receiving any other investigational agents
  • No uncontrolled intercurrent illness including, but not limited to:
    • Ongoing or active infection
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Uncontrolled symptomatic cardiac arrhythmia
    • Uncontrolled hypertension (defined as blood pressure > 160/90)
  • None of the following co-morbid conditions:
    • Cataracts of grade 2 or greater as per Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
    • Retinopathy of grade 2 or greater as per CTCAE version 4.0

      • Note: patients that have cataracts that do not require surgery are eligible
    • Deep vein thrombosis/pulmonary embolism (DVT/PE) within the past 6 months

      • Note: patients that are on anticoagulant therapy for maintenance are eligible as long as the DVT and/or PE occurred > 6 months prior to enrollment, and there is no evidence for active thrombosis (either DVT or PE)
  • No other active second malignancy other than non-melanoma skin cancers within 3 years of pre-registration; a second malignancy is not considered active if all treatment for that malignancy is completed and the patient has been disease-free for at least 3 years prior to pre-registration
  • Eastern Cooperative Oncology Group (ECOG) performance status: 0-2
  • Able to swallow oral formulation of the study agent
  • Hemoglobin >= 9 g/dL
  • Platelet count >= 75,000/mm^3
  • Creatinine =< 1.5 x upper limits of normal (ULN)
  • Total bilirubin =< 1.5 x upper limits of normal (ULN)
  • Aspartate aminotransferase (AST) =< 2.5 x upper limits of normal (ULN); for patients with liver metastasis: =< 5 x upper limits of normal (ULN)
  • REGISTRATION ELIGIBILITY CRITERIA
  • Patients with either measurable disease as defined by RECIST criteria or bone only disease are eligible; Note: those patients with both non-measurable disease and bone metastases are eligible
    • Non-measurable bone only disease: Non-measurable bone only disease may include any of the following: blastic bone lesions, lytic bone lesions without a measurable soft-tissue component, or mixed lytic-blastic bone lesions without a measurable soft-tissue component
    • Lytic bone lesions, with an identifiable soft tissue component, evaluated by computed tomography (CT) or magnetic resonance imaging (MRI), can be considered as measurable lesions if the soft tissue component otherwise meets the definition of measurability previously described
  • No tumors involving spinal cord or heart
  • No visceral crisis, lymphangitic spread or known brain metastases: visceral crisis is not the mere presence of visceral metastases, but implies severe organ dysfunction as assessed by symptoms and signs, laboratory studies, and rapid progression of disease
  • Histologic confirmation, from the A011203 pre-registration biopsy, by institutional/local pathologist of either locally advanced or metastatic breast cancer that is estrogen receptor positive and HER2 negative; those patients with bone only disease with either no tumor or insufficient tumor for ER/progesterone receptor (PR) and HER2 staining after the bone biopsy are still eligible to participate in this study
  • Estrogen receptor positive disease is defined as > 10% nuclear staining
  • HER2 negative disease as per 2013 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines, one of the following must apply:
    • 0 or 1+ by immunohistochemistry (IHC) and not amplified by in situ hybridization (ISH)
    • 0 or 1+ by IHC and ISH not done
    • 2+ by IHC and not amplified by ISH or
    • IHC not done and not amplified by ISH
  • None of the following therapies are allowed prior to registration:
    • Chemotherapy =< 2 weeks
    • Immunotherapy =< 2 weeks
    • Biologic therapy =< 2 weeks
    • Hormonal therapy =< 2 weeks
    • Monoclonal antibodies =< 2 weeks
    • Radiation therapy =< 2 weeks
    • Anti-Her-2 or other "targeted" (e.g. mammalian target of rapamycin [mTOR]) therapy =< 2 weeks
      • NOTE : Any toxicities derived from these therapies must be =< grade 2 prior to starting study therapy

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.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Jacksonville, Fla.

Mayo Clinic principal investigator

Matthew Goetz, M.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Rochester, Minn.

Mayo Clinic principal investigator

Matthew Goetz, M.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

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CLS-20143588

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