Re-expression of ER in Triple Negative Breast Cancers

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by Emory University
Sponsor:
Collaborators:
Novartis
Eisai Inc.
Information provided by (Responsible Party):
Ruth O'Regan, Emory University
ClinicalTrials.gov Identifier:
NCT01194908
First received: September 1, 2010
Last updated: November 18, 2013
Last verified: June 2013

September 1, 2010
November 18, 2013
July 2010
July 2015   (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. ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT01194908 on ClinicalTrials.gov 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. ] [ Designated as safety issue: Yes ]
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
Interventional
Phase 1
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Breast Cancer
  • Breast Tumors
  • Breast Neoplasms
Drug: Decitabine, LHB589, 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, LHB589, Tamoxifen
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
60
July 2016
July 2015   (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 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 DNMT and HDAC inhibitors are allowed.
  • Age > 18 years
  • ECOG Performance Score of 0 or 1 (Appendix A)
  • Adequate bone marrow as evidenced by:

    • Absolute neutrophil count > 1,500/uL
    • Platelet count > 100,000/uL
  • 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 < 3X the ULN for the reference lab (< 5X the ULN for patients with known hepatic metastases
    • SGOT/SGPT < 3X the ULN for the reference lab (< 5X 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 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 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)
Both
18 Years and older
No
Contact: Ruth O'Regan, MD 1-888-946-7447 roregan@emory.edu
United States
 
NCT01194908
IRB00029718, WCI1696-09
Yes
Ruth O'Regan, Emory University
Emory University
  • Novartis
  • Eisai Inc.
Principal Investigator: Ruth O'Regan, MD Emory University Winship Cancer Institute
Emory University
June 2013

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