Tamoxifen Citrate in Treating Patients with Stage III or IV Breast Cancer

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Basic Trial Information

PhaseTypeAgeTrial IDs
Phase IIBiomarker/Laboratory analysis, Treatment18 and overE3108
NCI-2011-02067, CDR0000672523, ECOG-E3108, NCT01124695

Trial Description

Summary

This phase II trial studies how well tamoxifen citrate works in patients with stage III or IV breast cancer. 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.

Further Study Information

PRIMARY OBJECTIVES:

I. To correlate cytochrome P450 2D6 (CYP2D6) score (0 vs. 1+2) and progression-free survival.

SECONDARY OBJECTIVES:

I. To correlate CYP2D6 score (0 vs. 1 vs. 2) and progression-free survival.

II. To correlate CYP2D6 score (0 vs. 1 + 2) and proportion of patients who are progression-free at 6 months.

III. To correlate endoxifen concentration with response.

IV. To correlate CYP2D6 score with response.

V. To correlate the presence of candidate estrogen receptor (ESR) 1 and 2 variant alleles, uridine 5'-diphosphosphate (UDP) glycosyltransferase 7 (UGT7), phenol sulfotransferase (SULT1A1), other candidate genes and biomarkers to progression-free survival and other tamoxifen related outcomes.

OUTLINE:

Patients receive tamoxifen citrate orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Eligibility Criteria

Inclusion Criteria:

Serum glutamic oxaloacetic transaminase (SGOT)(aspartate aminotransferase [AST]) =< 2.5 x upper limit of normal OR =< 5 x upper limit of normal if liver metastases

Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 2.5 x upper limit of normal OR =< 5 x upper limit of normal if liver metastases

Patients must have measurable or non-measurable stage III/locally advanced or metastatic carcinoma of the breast where surgery is not possible; lesions must be evaluated within 4 weeks prior to registration

Must have estrogen and/or progesterone receptor positive histologically confirmed adenocarcinoma of the breast; receptor status may be based on any time during treatment prior to study registration, and from any site (i.e. primary recurrent, or metastatic)

Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

Concurrent chemotherapy is not allowed

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

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

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)

Patients who have received agents that modulate or downregulate the estrogen receptor for breast cancer prevention (e.g. tamoxifen, raloxifene, fulvestrant) or bone health (raloxifene) are eligible if they were on treatment for at least 6 months, did not have a diagnosis of breast cancer on the medication, and have discontinued the agents 6 months prior to study registration

Prior tamoxifen is not allowed in the locally advanced or metastatic setting

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

Patients who have received other agents that modulate or downregulate the estrogen receptor (e.g. raloxifene, fulvestrant) in the adjuvant setting are eligible if they were on treatment for at least 6 months prior to disease progression in the locally advanced or metastatic setting

Patients who have received other agents that modulate or downregulate the estrogen receptor (e.g. raloxifene, fulvestrant) in the locally advanced or metastatic setting are eligible if they were on treatment for at least 6 months and must have discontinued these agents 6 months prior to study registration

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 agents; treatment in the locally advanced or metastatic setting must have been completed at least 2 weeks prior to study registration

Women must not be pregnant or breast-feeding; 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:

Has not undergone a hysterectomy or bilateral oopherectomy; Or

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)

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

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

Chemotherapy or trastuzumab or bevacizumab in the adjuvant setting is allowed but must have been completed at least 4 weeks prior to study registration; other prior non-hormonal investigational agents in the adjuvant setting must have completed at least 4 weeks prior to study registration and should be discussed with the study principal investigator (PI)

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

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

Non-protocol concurrent hormonal therapy is not allowed

Total bilirubin =< 1.5 x upper limit of normal

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

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 quindine (Cardioquin) within 2 weeks of registration

Patients may not initiate bisphosphonate or denosumab therapy while receiving treatment on this study; patients who have begun receiving bisphosphonate or denosumab therapy prior to registration may continue at the same intervals used prior to study registration

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators

ECOG-ACRIN Cancer Research Group

  • National Cancer Institute
Vered Stearns, Principal Investigator

Trial Sites

U.S.A.

Illinois
La Grange

Adventist La Grange Memorial Hospital

Renee Helene Jacobs
Ph: 630-856-7526

Renee Helene Jacobs
Principal Investigator

Massachusetts
Boston

Tufts Medical Center

John Kalil Erban
Ph: 617-636-5000
Email: ContactUsCancerCenter@TuftsMedicalCenter.org

John Kalil Erban
Principal Investigator

Minnesota
Fergus Falls

Lake Region Healthcare Corporation-Cancer Care

Preston D. Steen
Ph: 701-234-6161

Preston D. Steen
Principal Investigator

Ohio
Akron

Akron General Medical Center

Esther Hoogland Rehmus
Ph: 330-344-6348

Esther Hoogland Rehmus
Principal Investigator

Pennsylvania
Media

Riddle Memorial Hospital

Allison Maria Zibelli
Ph: 215-955-6084

Allison Maria Zibelli
Principal Investigator

Virginia
Charlottesville

Martha Jefferson Hospital

Robert S. Pritchard
Ph: 434-654-8400

Robert S. Pritchard
Principal Investigator

Wisconsin
Milwaukee

Froedtert and the Medical College of Wisconsin

Timothy Sean Fenske
Ph: 414-805-4380

Timothy Sean Fenske
Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01124695

Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.