Description:
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.
Title
- Brief Title: A Pilot Preoperative Trial of Ganetespib With Paclitaxel for Triple-Negative Breast Cancer
- Official Title: A Pilot Preoperative Trial of Ganetespib With Paclitaxel for Triple-Negative Breast Cancer
Clinical Trial IDs
- ORG STUDY ID:
IRB15-0848
- NCT ID:
NCT02637375
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Ganetespib | | Therapy |
Paclitaxel | | Therapy |
Doxorubicin | | Therapy |
Cyclophosphamide | | Therapy |
Purpose
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
Trial Arms
Name | Type | Description | Interventions |
---|
Therapy | Experimental | Patients will receive ganetespib monotherapy for two weeks followed by twelve weeks of ganetespib/paclitaxel therapy followed by 4 bi-weekly doses of doxorubicin/cyclophosphamide therapy followed by surgery. | - Ganetespib
- Paclitaxel
- Doxorubicin
- Cyclophosphamide
|
Eligibility Criteria
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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | Female |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Change in GR protein |
Time Frame: | 2 weeks |
Safety Issue: | |
Description: | |
Secondary Outcome Measures
Measure: | Pathological Complete Response (pCR) rate |
Time Frame: | 6 month |
Safety Issue: | |
Description: | Defined as absence of invasive carcinoma in both the breast and axilla at the time of surgery |
Measure: | Ganetespib toxicity |
Time Frame: | 14 weeks |
Safety Issue: | |
Description: | Side effects related to Ganetespib as graded per Common Terminology Criteria for Adverse Events (CTCAE) version 4 |
Details
Phase: | N/A |
Primary Purpose: | Interventional |
Overall Status: | Withdrawn |
Lead Sponsor: | University of Chicago |
Trial Keywords
- triple-negative breast cancer
Last Updated
May 30, 2016