Clinical trial NCT02637375: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Breast Cancer
Keywords: triple-negative breast cancer
Lead sponsor: University of Chicago
Sponsor class: OTHER
First posted: 2015-12-22
Enrollment: 0
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: Change in GR protein
timeFrame: 2 weeks
Secondary outcomes:
measure: Pathological Complete Response (pCR) rate
timeFrame: 6 month
measure: Ganetespib toxicity
timeFrame: 14 weeks
Other outcomes:
Locations:
Study officials:
affiliation: University of Chicago
name: Rita Nanda, MD
role: PRINCIPAL_INVESTIGATOR
References: