Title Phase II Prospective Trial Correlating Progression Free Survival with CYP2D6 Activity in Patients with Metastatic Breast Cancer Treated with Single Agent Tamoxifen


CC CC00096

Hospital Beachwood, Fairview, Hillcrest, Independence, Main Campus, North Coast Cancer, Strongsville, Wooster

Stage N/A

Phase Phase 2

Disease Breast

Drug Tamoxifen



  1. Primary Objective
    • To correlate CYP2D6 score (0 vs. 1+2) and progression-free survival.
  2. Secondary Objectives
    • To correlate CYP2D6 score (0 vs. 1 vs. 2) and progression-free survival.
    • To correlate CYP2D6 score (0 vs. 1 + 2) and proportion of patients who are progression-free at 6 months.
    • To correlate endoxifen concentration with response.
    • To correlate CYP2D6 score with response.
    • To correlate the presence of candidate estrogen receptor (ESR) 1 and 2 variant alleles, UGT7, SULT1A1, other candidate genes and biomarkers to progression-free survival and other tamoxifen related outcomes.
Inclusion Criteria

Inclusion Criteria

  1. Must have estrogen and/or progesterone receptor positive histologically confirmed adenocarcinoma of the breast.
  2. Patients must have measurable or non-measurable Stage III/locally advanced or metastatic carcinoma of the breast where surgery is not possible, as defined in Section 6.1.1. Lesions must be evaluated within 4 weeks prior to registration.
  3. Age ≥ 18 years.
  4. Women must not be pregnant or breast-feeding due to harmful effects of tamoxifen. Note: All females of childbearing potential must have a blood test within 2 weeks prior to registration to rule out pregnancy. A female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) Has not undergone a hysterectomy or bilateral oopherectomy; Or 2) Has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
  5. Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of non-hormonal contraception. Acceptable contraception includes barrier methods (e.g., condoms or diaphragm) or intrauterine devices or IUDs (these may include low-dose hormones at the discretion of the Study Chair).
  6. ECOG performance status of 0-2.
  7. Patient must not have had chemotherapy or trastuzumab (Herceptin) for metastatic disease. Chemotherapy or trastuzumab or bevacizumab in the adjuvant setting is allowed but must have been completed at least 6 weeks prior to study registration and discussed with the study PI. Prior investigational agents in the metastatic setting are not allowed. Other prior investigational agents in the adjuvant setting must have been completed at least 6 weeks prior to study registration and should be discussed with the study PI.
  8. Prior tamoxifen or other agents that modulate or downregulate the estrogen receptor (e.g. raloxifene, fulvestrant) are not allowed.
  9. Prior aromatase inhibitor (up to 2 agents) (e.g. anastrozole, letrozole, exemestane, aminoglutethamide) is allowed in the adjuvant or metastatic setting and must be discontinued at study registration.
  10. Non-protocol concurrent hormonal therapy is not allowed.
  11. Concurrent chemotherapy is not allowed.
  12. Patients, must have adequate hematologic and renal function at the discretion of the treating physician and hepatic function as defined by the following within 4 weeks prior to registration:
    • Total bilirubin ≤ 1.5 x upper limit of normal
    • SGPT (ALT) ≤ 2.5 x upper limit of normal.
    • SGOT (AST) ≤ 2.5 x upper limit of normal.
  13. Patients with a history of central nervous system metastasis are allowed provided they have been treated (surgery, radiation, or radiosurgery) at least 4 weeks prior to initiating study drug and do not require medication(s) to control symptoms. Patients with known leptomeningeal disease are not eligible.
  14. Patients may receive concurrent radiation therapy to painful sites of bony disease or areas of impending fracture as long as the radiation therapy is initiated prior to study entry and sites of measurable and non-measurable disease outside the radiation therapy port are available to follow. Patients who have received prior radiation therapy must have recovered from toxicity of the prior radiation therapy.
  15. Patients must not take the following medications that are strong to moderate inhibitors of CYP2D6 and may alter tamoxifen metabolism: paroxetine (Paxil), fluoxetine (Prozac), buproprion (Wellbutrin) and quinidine (Cardioquin) within 2 weeks of registration.
  16. Patients must not suffer from medical or psychiatric conditions that would interfere with protocol compliance, the ability to provide informed consent, or assessment of response or anticipated toxicities.
  17. Patients must be disease-free of prior invasive malignancies for ≥ 5 years with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
  18. Patients may not initiate bisphosphonate therapy while receiving treatment on this study. Patients who have begun receiving bisphosphonate therapy prior to registration may continue at the same intervals used prior to study registration.
Exclusion Criteria

Exclusion Criteria

Exclusion Criteria Not Available