Breast Cancer
Conditions
Keywords
triple-negative breast cancer
Brief summary
Based on preclinical data implicating GR, AR, and JAK/STAT activation as potent mechanisms of breast cancer cell survival despite chemotherapy administration (i.e. chemotherapy resistance), the study will test a novel approach for improving chemotherapy effectiveness by adding Hsp90 inhibition to antagonize the anti-apoptotic signaling pathways that are initiated via GR, AR, and JAK/STAT activation.
Detailed description
STUDY OBJECTIVES Primary: • To determine tumor GR, AR, JAK and other Hsp90 client protein expression before and after two weeks of ganetespib monotherapy Secondary: * To determine the pathological Complete Response (pCR) rate associated with weekly treatment of ganetespib plus paclitaxel followed by the combination treatment of doxorubicin plus cyclophosphamide * To characterize the toxicity of study treatment
Interventions
Sponsors
University of Chicago
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Invasive carcinoma of the breast * ER negative and PR negative tumors defined as \< 1% of tumor nuclei that are immunoreactive for ER and PR * HER2 non-overexpressing status documented as: * FISH ratio of less than 2.0, OR * IHC staining of 0 or 1+ * No evidence of distant metastatic disease. Patients with regional lymph node involvement are eligible. * \>18 years old * Female * No prior treatment for the disease under study * No prior treatment within 5 years for any other cancer including chemotherapy, surgery (except for diagnostic biopsy), radiotherapy, hormonal therapy, or investigational agents, unless curative treatment of non-melanoma skin-cancer or in-situ cancer * Able to understand and sign an informed consent (or have a legal representative who is able to do so) * Clinically or radiologically measureable disease in the breast after diagnostic biopsy, defined as longest diameter greater than or equal to 2cm * Willing to undergo three mandatory core biopsies after diagnosis to obtain tissue for biologic expression profiling. * An Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1 * Adequate bone marrow reserves as evidenced by: * Leukocytes \> 3,000/μL * Absolute neutrophil count (ANC) \> 1,500/μL without the use of hematopoietic growth factors, * Platelet count \> 100,000/μL, and * Hemoglobin \> 9 g/dL * Adequate hepatic function as evidenced by: * Serum total bilirubin within institutional normal limits * Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase less than or equal to 2.5 × ULN * Adequate renal function as evidenced by a serum creatinine within ULN or creatinine clearance \> 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal * Eligible for treatment with paclitaxel, doxorubicin and cyclophosphamide * If of childbearing potential, are willing to abstain from sexual intercourse or to use an effective form of contraception (e.g., a double-barrier method) during the study and for 90 days following the last dose of ganetespib
Exclusion criteria
* • Patients may not be receiving any other investigational agents. * Patients may not have a known hypersensitivity to any of the components of ganetespib * Patients may not have a history of severe allergic reactions to paclitaxel or other drugs formulated in Cremaphor® EL. * Patients with a QTc \> 470 ms, a family history of long QT Syndrome, and those on medications known to cause Torsades de Pointes will be excluded from the study. * Patients may 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 New York Heart Association (NYHA) Class III or IV congestive heart failure or left ventricular ejection fraction (LVEF) \< 50%. * As patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study. * Patients may not have a need for chronic systemic steroid therapy * Patients may not be pregnant or breastfeeding
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in GR protein | 2 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pathological Complete Response (pCR) rate | 6 month | Defined as absence of invasive carcinoma in both the breast and axilla at the time of surgery |
| Ganetespib toxicity | 14 weeks | Side effects related to Ganetespib as graded per Common Terminology Criteria for Adverse Events (CTCAE) version 4 |
Outcome results
None listed