Re-expression of ER in Triple Negative Breast Cancers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01194908
Recruitment Status : Terminated (Slow accrual)
First Posted : September 3, 2010
Results First Posted : January 26, 2015
Last Update Posted : January 26, 2015
Eisai Inc.
Information provided by (Responsible Party):
Ruth O'Regan, Emory University

September 1, 2010
September 3, 2010
January 18, 2015
January 26, 2015
January 26, 2015
July 2010
January 2014   (Final data collection date for primary outcome measure)
To Determine the Maximum Tolerated Dose of Decitabine and LBH589 Given in Combination in Patients With Metastatic or Locally Advanced Metastatic Breast Cancers [ Time Frame: Estrogen receptor status checked 5 days after treatment. Staging is done every 8 weeks. ]
Same as current
Complete list of historical versions of study NCT01194908 on Archive Site
To Determine the Safety of Tamoxifen in Combination With Decitabine and LBH589 [ Time Frame: Patients will undergo an evaluation for extent of disease 8 weeks from starting study drugs and every 8 weeks (2 cycles) while on study. ]
Same as current
Not Provided
Not Provided
Re-expression of ER in Triple Negative Breast Cancers
Phase I/II Trial of Tamoxifen Following Epigenetic Regeneration of Estrogen Receptor Using Decitabine and LBH 589 in Patients With Triple Negative Metastatic Breast Cancer

Patients are being asked to take part in this study because they have metastatic breast cancer that is triple negative (does not express estrogen receptor (ER), progesterone receptor (PR) or HER2). This means that agents such as trastuzumab (Herceptin®) and tamoxifen are not currently treatment options for their cancer. Another option for treating the patient's cancer at this point is with chemotherapy. The patient should discuss this and other options with their doctor prior to entering this study.

Laboratory studies have demonstrated that ER is actually present in some triple negative breast cancers but is "silenced" (does not function properly) because methyl and histone groups are attached to it and inactivate it. Special drugs called demethylating inhibitors (such as decitabine) and histone deacetylase inhibitors (such as LBH589) can remove these methyl and histone groups and reactivate ER. This reactivated ER can then be targeted with agents like tamoxifen.

The patient is being asked to join this clinical research study to find out if ER can be reactivated in their cancer using decitabine in combination with LBH589. If ER is reactivated in their cancer, we will then determine if tamoxifen can decrease the growth of the cancer.

Not Provided
Phase 1
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Breast Cancer
  • Breast Tumors
  • Breast Neoplasms
Drug: Decitabine, LBH589, Tamoxifen

Dose level -1; Decitabine (IV)(D1-5): 5mg/m2; LBH589 (IV)(D1,8): 10mg/m2

Dose level 0; Decitabine (IV)(D1-5): 10mg/m2; LBH589 (IV)(D1,8): 10mg/m2

Dose level +1; Decitabine (IV)(D1-5): 10mg/m2; LBH589 (IV)(D1,8): 15mg/m2

Dose level +2; Decitabine (IV)(D1-5): 10mg/m2; LBH589 (IV)(D1,8): 20mg/m2

Dose level +3; Decitabine (IV)(D1-5): 15mg/m2; LBH589 (IV)(D1,8): 20mg/m2

Dose level +4; Decitabine (IV)(D1-5): 20mg/m2; LBH589 (IV)(D1,8): 20mg/m2

Other Names:
  • LBH589
  • Decitabine
  • Dacogen
  • Novaldex
Experimental: Arm A
Patients treated with decitabine and LBH589
Intervention: Drug: Decitabine, LBH589, Tamoxifen
Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
January 2014
January 2014   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Histologically or cytologically confirmed triple negative (ER-, PR-, HER2-) metastatic or locally advanced breast cancer
  • Measurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
  • Disease that is assessable to biopsy for hormone receptor measurement
  • At least one line of therapy prior to study entry (acceptable therapies include chemotherapy ± anti-angiogenic therapy). Other investigational therapies except DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibitors are allowed.
  • Age > 18 years
  • Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1 (Appendix A)
  • Adequate bone marrow as evidenced by:

    • Absolute neutrophil count > 1,500/μL
    • Platelet count > 100,000/μL
  • Adequate renal function as evidenced by serum creatinine < 1.5 mg/dL
  • Adequate hepatic function as evidenced by:

    • Serum total bilirubin < 1.5 mg/dL
    • Alkaline phosphatase < 3 times the upper limit of normal (ULN) for the reference lab (< 5 times the ULN for patients with known hepatic metastases
    • Serum glutamic-oxaloacetic transaminase (SGOT)/serum glutamic-pyruvic transaminase (SGPT) < 3 times the ULN for the reference lab (< 5 times the ULN for patients with known hepatic metastases
  • Patients must be recovered from both the acute and late effects of any prior surgery, radiotherapy or other antineoplastic therapy
  • Patients or their legal representatives must be able to read, understand and provide informed consent to participate in the trial.
  • Consent to biopsy before and after therapy with decitabine and LBH589.
  • Patients of childbearing potential and their partners must agree to use an effective form of contraception during the study and for 90 days following the last dose of study medication (an effective form of contraception is an oral contraceptive or a double barrier method)

Exclusion Criteria:

  • Patients with an active infection or with a fever > 101.30 F within 3 days of the first scheduled day of protocol treatment
  • Patients with active central nervous system (CNS) metastases. Patients with stable CNS disease, who have undergone radiotherapy at least 4 weeks prior to the planned first protocol treatment and who have been on a stable dose of corticosteroids for >3 weeks are eligible for the trial
  • History of prior malignancy within the past 5 years except for curatively treated basal cell carcinoma of the skin, cervical intra-epithelial neoplasia, or localized prostate cancer with a current prostate-specific antigen (PSA) of < 1.0 mg/dL on 2 successive evaluations, at least 3 months apart, with the most recent evaluation no more than 4 weeks prior to entry
  • Patients with known hypersensitivity to any of the components of decitabine or LBH589
  • Patients who received radiotherapy to more than 25% of their bone marrow; or patients who received any radiotherapy within 4 weeks of entry
  • Patients who are receiving concurrent investigational therapy or who have received investigational therapy within 28 days of the first scheduled day of protocol treatment (investigational therapy is defined as treatment for which there is currently no regulatory authority approved indication)
  • Peripheral neuropathy >= Grade 2
  • Patients who are pregnant or lactating
  • Any other medical condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results.
  • History of allogeneic transplant
  • Known HIV or Hepatitis B or C (active, previously treated or both)
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
Contact information is only displayed when the study is recruiting subjects
United States
WCI1696-09 ( Other Identifier: Other )
Not Provided
Not Provided
Ruth O'Regan, Emory University
Emory University
  • Novartis
  • Eisai Inc.
Principal Investigator: Ruth O'Regan, MD Emory University Winship Cancer Institute
Emory University
January 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP