Description:
This study will help to understand the interaction between estrogen receptor-alpha (ER alpha)
and tumor suppressor protein p53 as well as impact on patient tumor gene expression in
response to the hormonal therapy Tamoxifen. This information may eventually help select the
appropriate therapy for future patients with similar cancer.
Title
- Brief Title: Analyzing a New Mechanism in Response to Tamoxifen Therapy in Breast Cancer Patients
- Official Title: Pilot Study to Analyze a Novel Mechanism Underlying Response to Tamoxifen Therapy in Breast Cancer Patients
Clinical Trial IDs
- ORG STUDY ID:
RPCI I 110907
- SECONDARY ID:
R21CA137635-01A1
- NCT ID:
NCT01027416
- NCT ALIAS:
NCT01658566
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Tamoxifen | | Tamoxifen |
Purpose
This study will help to understand the interaction between estrogen receptor-alpha (ER alpha)
and tumor suppressor protein p53 as well as impact on patient tumor gene expression in
response to the hormonal therapy Tamoxifen. This information may eventually help select the
appropriate therapy for future patients with similar cancer.
Detailed Description
Women with abnormal mammogram or suspicious masses will undergo diagnostic core biopsies
which will be analyzed for ER/PR and HER2Neu expression. For patients that are ER positive,
p53 staining will be done.
Women presenting tumors with an Allred score of 3 or greater status will be approached to
participate.
Women will be randomized to either standard of care surgical therapy or a 4 week intervention
of Tamoxifen 20mg daily for 4 weeks prior to surgery. During the intervention, blood draws
will be done to measure levels of tamoxifen metabolites in the blood and test for
polymorphisms that may decrease levels of active metabolites.
Women will undergo two blood draws for PK/PD and one for pharmacogenomics. Tissue microarray
(TMA) will be generated from resected tumors for immunohistochemistry (IHC) and proximity
ligation assay (PLA) for measuring ER alpha-p53 interaction.
Tumor tissue will be used for analyzing tamoxifen metabolites and estradiol levels. RNA and
proteins from the tumors will be used for analyzing gene expression.
Trial Arms
Name | Type | Description | Interventions |
---|
No Intervention | No Intervention | | |
Tamoxifen | Active Comparator | Tamoxifen 20 mg orally 1x/day for 4 weeks | |
Eligibility Criteria
Inclusion Criteria:
1. The patient must consent to be in the study and must have signed an approved consent
form conforming to institutional guidelines
2. The patient must be 18 years or older.
3. Core biopsy should definitively demonstrate invasive carcinoma.
4. Invasive carcinoma should be ER-apha receptor positive
5. The tumor should be approximately at least 1 cm, to account for variability in imaging
and imaging occult disease (physical exam, mammography, ultrasound). We recognize that
from time to time because of this variation, there might not be enough tissue
available for analysis after surgical excision but this will allow the greatest
opportunity to capture as many eligible patients as possible.
6. Patients in whom surgical excision of the tumor is part of standard of care management
7. ECOG score of 0 or 1
8. Negative serum or urine beta-hCG pregnancy test at screening for patients of
child-bearing potential (this is routinely done if the patient is premenopausal and
having surgery)
9. Consent to participate in DBBR (RPCI only)
Exclusion Criteria:
1. Male patients are not eligible for this study
2. Female patients with inoperable tumors or women with stage 4 disease diagnosed on CT,
PET, PET/CT or bone scan.
3. Patients with diagnosis by FNA cytology only
4. Pregnant or lactating women
5. Prior therapy for breast cancer, including irradiation, chemo- immuno- and/or hormonal
therapy
6. Patients receiving any hormonal therapy, e.g. ovarian hormonal replacement therapy,
infertility medications etc., are not eligible
7. Nonmalignant systemic disease (cardiovascular, renal, hepatic, etc.) that would
preclude the patient from being subjected to surgical excision
8. Psychiatric or addictive disorders that would preclude obtaining informed consent
9. Patients known or suspected to have hypercoagulable syndrome or with history of venous
or arterial thrombosis, stroke, TIA, or pulmonary embolism
10. Women with non-invasive disease or microinvasion are not eligible.
11. Women undergoing neoadjuvant chemotherapy are not eligible
12. women currently on tamoxifen and raloxifene for prevention are not eligible
13. Patients shall not receive any herbal/alternative therapies such as flaxseed or soy
products or black cohosh.
14. Patients with a known mutation in p53 (Li Fraumeni Syndrome)
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | Female |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Mean Percent Positive Proximity Ligation Assays of All Tumor Protein p53-wild Type Breast Tumors in Participants by Treatment Arm |
Time Frame: | 2 years |
Safety Issue: | |
Description: | Status of estrogen receptor alpha (ERά) and tumor protein (p53) interaction in p53-wild type breast tumors in untreated patients verses patients treated with tamoxifen. Mean percent positive polylactide (PLA) of all p53-wild type breast tumors in participants by treatment arm |
Secondary Outcome Measures
Measure: | Total Number of Over-expressed Genes, Across All Participants With Tumor Protein p53-wild Type Breast Tumors That Had RNA Samples Available. |
Time Frame: | 2 years |
Safety Issue: | |
Description: | Total number of over-expressed genes, across all participants with tumor protein p53-wild type breast tumors that had ribonucleic acid (RNA) samples available. |
Details
Phase: | N/A |
Primary Purpose: | Interventional |
Overall Status: | Completed |
Lead Sponsor: | Roswell Park Cancer Institute |
Trial Keywords
Last Updated
December 13, 2017