Re-expression of ER in Triple Negative Breast Cancers

This study has been terminated.
(Slow accrual)
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: August 29, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Breast Tumors
Breast Neoplasms
Drug: Decitabine, LBH589, Tamoxifen
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 5
Study Start Date: July 2010
Study Completion Date: January 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A
Patients treated with decitabine and LBH589
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01194908

Locations
United States, Georgia
Emory University Winship Cancer Institute
Atlanta, Georgia, United States, 30329
Sponsors and Collaborators
Emory University
Novartis
Eisai Inc.
Investigators
Principal Investigator: Ruth O'Regan, MD Emory University Winship Cancer Institute
  More Information

No publications provided

Responsible Party: Ruth O'Regan, Physician, Emory University
ClinicalTrials.gov Identifier: NCT01194908     History of Changes
Other Study ID Numbers: IRB00029718, WCI1696-09
Study First Received: September 1, 2010
Last Updated: August 29, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Emory University:
Breast Cancer
Breast Tumors
Breast Neoplasms

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms
Triple Negative Breast Neoplasms
Breast Diseases
Neoplasms by Site
Skin Diseases
Decitabine
Panobinostat
Tamoxifen
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Bone Density Conservation Agents
Enzyme Inhibitors
Estrogen Antagonists
Estrogen Receptor Modulators
Histone Deacetylase Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Selective Estrogen Receptor Modulators
Therapeutic Uses

ClinicalTrials.gov processed this record on October 30, 2014