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.
PURPOSE: This phase II trial is studying how well tamoxifen citrate works in patients with metastatic or recurrent breast cancer.
Brief Title
Tamoxifen Citrate in Treating 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.
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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Breast Cancer
Stage IV Breast Cancer
Eligibility Criteria
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
* 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
Inclusion Criteria
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
* 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
Gender
All
Gender Based
false
Keywords
estrogen receptor-positive breast cancer
progesterone receptor-positive breast cancer
recurrent breast cancer
stage IV breast cancer
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT01124695
Org Class
Network
Org Full Name
Eastern Cooperative Oncology Group
Org Study Id
E3108
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase II Prospective Trial Correlating Progression Free Survival With CYP2D6 Activity in Patients With Metastatic Breast Cancer Treated With Single Agent Tamoxifen
Primary Outcomes
Outcome Description
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.
Outcome Measure
Progression-free Survival by CYP2D6 Status in 2 Categories
Outcome Time Frame
Assessed every 3 months for 2 years, then every 6 months up to 5 years
Secondary Ids
Secondary Id
E3108
Secondary Id
U10CA180794
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
Assessed every 3 months for 2 years, then every 6 months up to 5 years
Outcome Measure
Progression-free Survival by CYP2D6 Status in 3 Categories
Outcome Description
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.
Outcome Time Frame
Assessed every 3 months for 6 months
Outcome Measure
Proportion of Patients Progression-free at 6 Months
Outcome Description
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.
Outcome Time Frame
Assessed every 3 months for 2 years, then every 6 months up to 5 years
Outcome Measure
Proportion of Patients With Response
Outcome Description
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.
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.
Outcome Time Frame
Endoxifen was assessed at cycle 3; response was assessed every 3 months for 2 years, then every 6 months up to 5 years
Outcome Measure
Endoxifen Concentration by Response
Outcome Description
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.
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.
Outcome Time Frame
Assessed every 3 months for 2 years, then every 6 months up to 5 years
Outcome Measure
Progression-free Survival From 3 Months Post Registration
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Della Makower
Investigator Email
DMAKOWER@montefiore.org
Investigator Phone