Clinical Trials /

Analyzing a New Mechanism in Response to Tamoxifen Therapy in Breast Cancer Patients

NCT01027416

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Completed

Phase:

N/A

Trial Eligibility

Document

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

  • Breast Cancer

Interventions

DrugSynonymsArms
TamoxifenTamoxifen

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

NameTypeDescriptionInterventions
No InterventionNo Intervention
    TamoxifenActive ComparatorTamoxifen 20 mg orally 1x/day for 4 weeks
    • Tamoxifen

    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

    • ER positive
    • Tamoxifen

    Last Updated

    November 15, 2017