Tamoxifen Citrate in Treating Patients With Metastatic or Recurrent Breast Cancer

ECOG-ACRIN Cancer Research Group

Status and phase: Completed; Phase 2

Conditions: Breast Cancer; Stage IV Breast Cancer

Treatments: Drug: tamoxifen

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT01124695

U10CA180794 (U.S. NIH Grant/Contract)

E3108 (Other Identifier)

Details and patient eligibility

About

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.

Full description

OBJECTIVES:

Primary

• To correlate CYP2D6 (Cytochrome P450 2D6) score (0 vs 1-2) and progression-free survival (PFS)

Secondary

• To correlate CYP2D6 score (0 vs 1 vs 2) and PFS
• To correlate CYP2D6 score (0 vs 1-2) and the proportion of these patients who are progression-free at 6 months.
• To correlate endoxifen concentration with response
• To correlate CYP2D6 with response
• To correlate the presence of candidate estrogen receptor (ESR) 1 and 2 variant alleles, UDP-glucuronosyltransferases (UGT) 7, sulfotransferases (SULT) 1A1, other candidate genes and biomarkers to PFS and other tamoxifen related outcomes

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.

Enrollment: 124 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion 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

• Measurable or non-measurable disease

• ECOG performance status 0-2

• History of central nervous system (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

• Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

• Alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 2.5 times ULN (≤ 5 times ULN if liver metastases present)

• Negative pregnancy test

• Fertile patients must use effective nonhormonal contraception

• 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

• Prior chemotherapy, trastuzumab, or bevacizumab in the adjuvant setting allowed provided it has been completed ≥ 4 weeks before study therapy; other prior non-hormonal investigational agents in the adjuvant setting must have been completed at least 4 weeks prior to study registration and should be discussed with the study PI

• 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 dose

• 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)

• 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

Exclusion criteria

• Pregnant or nursing

• Concurrent chemotherapy

• Leptomeningeal disease

• Non-protocol concurrent hormonal therapy

• Medical or psychiatric conditions that would interfere with protocol compliance, the ability to provide informed consent, assessment of response, or anticipated toxicities

• Prior tamoxifen for advanced disease

• More than 2 lines of non-hormonal treatment in the locally advanced or metastatic setting, including trastuzumab (Herceptin), bevacizumab, or other biologics

• Starting 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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124 participants in 1 patient group

Tamoxifen

Experimental group

Description:

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.

Treatment:

Drug: tamoxifen