Study Of MK-0752 In Combination With Tamoxifen Or Letrozole to Treat Early Stage Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: MK-0752
Intervention description: Women who are post menopausal will receive letrozole 2.5 mg by mouth one time per day for 24 days. Women who are pre menopausal, or who have a contraindication to letrozole will receive tamoxifen 20 mg orally one time per day for a period of 24 days. Starting on day 15 of this 24 day period all patients will receive the oral gamma-secretase inhibitor drug MK-0752 at a dose of 350 mg for three days on, then off four days, then three days on, for a total of 6 doses over a period of 10 days.
Intervention MeSH terms: 3-(4-((4-chlorophenyl)sulfonyl)-4-(2,5-difluorophenyl)cyclohexyl)propanoic acid
Phase: Phase 4
Study type: Interventional
Primary purpose: Other
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 22.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: MK-0752; Tamoxifen; Letroxole

Summary:

      The purpose of this research project is to study the effect of a research (investigational)
      drug, MK-0752 combined with either tamoxifen or letrozole on breast cancer cells.

      Tamoxifen and letrozole are standard hormone treatments used to treat breast cancers that are
      positive for the estrogen receptor. However, over time the breast cancer cells can become
      resistant to tamoxifen and letrozole. MK-0752 is in a class of drugs called gamma secretase
      inhibitors. Gamma secretase inhibitors may play a role in reversing the resistance to drugs
      such as tamoxifen and letrozole.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed early stage, ER-positive
             (Allred score ≥3), invasive breast cancer that is not either locally advanced by
             criteria other than size or inflammatory, and is not metastatic. - Patients must be
             candidates for surgical removal of the tumor by lumpectomy or mastectomy.

          -  Patients must not have bilateral tumors. Tumor must be amenable to core biopsy in
             midstudy.

          -  Patients must be >18 years of age.

          -  Patients must have a performance status ≤1 by Zubrod criteria.

          -  Patients must have a life expectancy of greater than three months.

          -  Patients must have normal organ and marrow function within 28 days of registration as
             defined below:

               -  absolute neutrophil count >1,500/μL

               -  platelets >100,000/μL

               -  total bilirubin ≤1.5 x the institutional upper limit of normal

               -  AST(SGOT)/ALT(SGPT) <2 X institutional upper limit of normal

               -  creatinine within normal institutional limits OR

               -  creatinine clearance >60 mL/min/1.73 m2 for patients with creatinine levels above
                  institutional normal

          -  Women of child-bearing potential must agree to use adequate contraception (hormonal or
             barrier method of birth control; abstinence) prior to study entry and for the duration
             of study participation. A negative serum pregnancy test must be obtained within 72
             hours of receiving the first dose of the hormonal therapy as well as within 72 hours
             of the first dose of the MK-0752 GSI medication for women of child-bearing potential.
             Should a woman become pregnant or suspect she is pregnant while participating in this
             study, she should inform her treating physician immediately.

        Exclusion Criteria:

          -  Patients may not have received any prior chemotherapy or endocrine therapy (tamoxifen,
             raloxifene, or an aromatase inhibitor) and may not have received prior therapy with a
             gamma-secretase inhibitor or other investigational agents. - Patients may not have
             received previous radiation therapy.

          -  Patients may not be currently participating or have participated in a study with an
             investigational compound or device within 30 days.

          -  Patients must not have known brain or CNS disease, evidence of brain or CNS
             metastases, or carcinomatous meningitis.

          -  Patients must not have an uncontrolled intercurrent illness including, but not limited
             to, ongoing or active infection, symptomatic congestive heart failure, unstable angina
             pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would
             limit compliance with study requirements.

          -  Patients may not have known hypersensitivity to the components of MK-0752 or it
             analogs.

          -  Patients will be excluded if there is a known history of human immunodeficiency (HIV)
             virus infection, or a known history of hepatitis B or C infection.

          -  Patients must not have a previous history of inflammatory bowel disease or
             uncontrolled irritable bowel syndrome.

          -  Patients must not have a history of greater than one basal cell carcinoma of the skin
             within the past five years or a history of Gorlin syndrome.