Tamoxifen Citrate in Treating Patients With Metastatic or Recurrent Breast Cancer


Breast Cancer

Trial Phase

Phase 2

Trial Purpose and Description

Trial Purpose

RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using tamoxifen citrate may fight cancer by blocking the use of estrogen by tumor cells.

PURPOSE: This phase II trial is studying how well tamoxifen citrate works in patients with metastatic or recurrent breast cancer.

Trial Description



  • To correlate CYP2D6 score (0 vs 1-2) and progression-free survival (PFS) of patients with metastatic breast cancer treated with tamoxifen citrate.


  • To correlate CYP2D6 score (0 vs 1 vs 2) and PFS of patients treated with this regimen.
  • To correlate CYP2D6 score (0 vs 1 + 2) and the proportion of these patients who are PFS at 6 months.
  • To correlate endoxifen concentration with response in patients treated with this regimen.
  • To correlate CYP2D6 with response in patients treated with this regimen.
  • To correlate the presence of candidate estrogen receptor (ESR) 1 and 2 variant alleles, UGT7, SULT1A1, and other candidate genes to PFS.

OUTLINE: This is a multicenter study.

Patients receive oral tamoxifen citrate once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicities.

Blood, plasma, and tissue samples are collected periodically for laboratory studies.

After completion of study therapy, patients are followed up every 3-6 months for 5 years.

Participation Guidelines

18 Years - N/A

Eligibility Criteria


- Histologically confirmed adenocarcinoma of the breast

- Stage III (locally advanced), metastatic, or recurrent disease

- Deemed not resectable

- Estrogen-receptor and/or progesterone-receptor positive disease

- Receptor status is based on most recent results

- Receptor testing on metastatic disease is not required

- Measurable or non-measurable disease

- History of CNS metastasis allowed provided it has been treated (surgery,
radiotherapy, or radiosurgery) within the past 4 weeks and does not require
medications to control symptoms

- No known leptomeningeal disease allowed


- ECOG performance status 0-2

- Menopausal status not specified

- Total bilirubin = 1.5 times upper limit of normal (ULN)

- ALT and AST = 2.5 times ULN (= 5 times ULN if liver metastases present)

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective nonhormonal contraception

- No medical or psychiatric conditions that would interfere with protocol compliance,
the ability to provide informed consent, assessment of response, or anticipated

- More than 5 years since prior invasive malignancies except curatively treated basal
cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix


- See Disease Characteristics

- No prior investigational agents in the metastatic setting

- Other prior investigational agents in any setting must have been completed at
least 6 weeks prior to study registration and should be discussed with the study

- Prior tamoxifen as adjuvant treatment is allowed as long as the patient did not have
disease relapse or progression while on adjuvant tamoxifen or within 4 weeks of last

- Prior tamoxifen for advanced disease is not allowed

- No prior chemotherapy or trastuzumab (Herceptin) for metastatic disease

- Prior chemotherapy, trastuzumab, or bevacizumab in the adjuvant setting allowed
provided it has been completed = 4 weeks before study therapy

- Patients must not have had more than 2 lines of non-hormonal treatment in the locally
advanced or metastatic setting, including trastuzumab (Herceptin), bevacizumab, or
other biologics

- Treatment in the advanced setting must have been completed at least 2 weeks
prior to study initiation

- Prior aromatase inhibitors (e.g., anastrozole, letrozole, exemestane,
aminoglutethamide) are allowed in the adjuvant or metastatic setting

- At least 2 weeks since prior and no concurrent medications that are strong to
moderate inhibitors of CYP2D6 and may alter tamoxifen citrate metabolism including,
but not limited to, any of the following:

- Paroxetine (Paxil)

- Fluoxetine (Prozac)

- Bupropion (Wellbutrin)

- Quinidine (Cardioquin)

- Patients may not initiate bisphosphonate therapy while receiving treatment on this

- Patients who have begun receiving bisphosphonate therapy prior to registration
may continue at the same intervals used prior to study registration

- Concurrent radiotherapy to painful sites of bone disease or areas of impending
fractures allowed provided the following criteria are met:

- Radiotherapy was initiated before study entry

- Sites of measurable or non-measurable disease are outside the radiotherapy port

- Recovered from prior radiotherapy

- No other concurrent hormonal therapy

- No concurrent chemotherapy
Eastern Cooperative Oncology Group
National Cancer Institute (NCI)
September 2010
Last Updated:
December 6, 2012
Study HIC#:

Clinicaltrials.gov ID: NCT01124695