Tamoxifen Citrate in Treating Patients With Metastatic or Recurrent Breast Cancer

Phase 2

Completed

Conditions: Breast Cancer
Stage IV Breast Cancer

Interventions: Drug: tamoxifen

Registration Number: NCT01124695

Lead Sponsor: ECOG-ACRIN Cancer Research Group

Brief Summary: 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.

Detailed 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 124

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Tamoxifen	tamoxifen	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.

Primary Outcome Measures

Name	Time	Method
Progression-free Survival by CYP2D6 Status in 2 Categories	Assessed every 3 months for 2 years, then every 6 months up to 5 years	Progression-free survival is defined as the time from registration to progression or death, whichever occurs first. Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) was used to evaluate progression. Progression is defined as appearance of one or more new lesions or unequivocal progression of existing non-target lesions or at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

Secondary Outcome Measures

Name	Time	Method
Progression-free Survival by CYP2D6 Status in 3 Categories	Assessed every 3 months for 2 years, then every 6 months up to 5 years	Progression-free survival is defined as the time from registration to progression or death, whichever occurs first. Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) was used to evaluate progression. Progression is defined as appearance of one or more new lesions or unequivocal progression of existing non-target lesions or at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Proportion of Patients With Response	Assessed every 3 months for 2 years, then every 6 months up to 5 years	Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) was used to evaluate response. Either complete response (CR) or partial response (PR) is considered as response. CR is defined as disappearance of all lesions. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Progression-free Survival From 3 Months Post Registration	Assessed every 3 months for 2 years, then every 6 months up to 5 years	This is a landmark progression-free survival analysis at 3 months post registration. Only patients who were progression-free and alive at 3 months were included. Progression-free survival in this analysis is defined as the time from 3 months post registration to progression or death, whichever occurs first. Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) was used to evaluate progression. Progression is defined as appearance of one or more new lesions or unequivocal progression of existing non-target lesions or at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Proportion of Patients Progression-free at 6 Months	Assessed every 3 months for 6 months	Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) was used to evaluate progression. Progression is defined as appearance of one or more new lesions or unequivocal progression of existing non-target lesions or at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Endoxifen Concentration by Response	Endoxifen was assessed at cycle 3; response was assessed every 3 months for 2 years, then every 6 months up to 5 years	Endoxifen (ng/ml) was assessed at cycle 3. Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) was used to evaluate response. Either complete response (CR) or partial response (PR) is considered as response. CR is defined as disappearance of all lesions. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Trial Locations

Locations (294): UAB Comprehensive Cancer Center
🇺🇸
Birmingham, Alabama, United States
University of South Alabama Mitchell Cancer Institute
🇺🇸
Mobile, Alabama, United States
Hembree Mercy Cancer Center at St. Edward Mercy Medical Center
🇺🇸
Fort Smith, Arkansas, United States
Tibotec Therapeutics - Division of Ortho Biotech Products, LP
🇺🇸
Marysville, California, United States
Mercy Cancer Center at Mercy Medical Center
🇺🇸
Merced, California, United States
Camino Medical Group - Treatment Center
🇺🇸
Mountain View, California, United States
St. Joseph Hospital Regional Cancer Center - Orange
🇺🇸
Orange, California, United States
Palo Alto Medical Foundation
🇺🇸
Palo Alto, California, United States
Valley Medical Oncology Consultants - Pleasanton
🇺🇸
Pleasanton, California, United States
University of California Davis Cancer Center
🇺🇸
Sacramento, California, United States
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UAB Comprehensive Cancer Center
🇺🇸Birmingham, Alabama, United States