Clinical Trials /

A Pilot Preoperative Trial of Ganetespib With Paclitaxel for Triple-Negative Breast Cancer

NCT02637375

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Withdrawn

Phase:

N/A

Trial Eligibility

Document

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

  • Breast Cancer

Interventions

DrugSynonymsArms
GanetespibTherapy
PaclitaxelTherapy
DoxorubicinTherapy
CyclophosphamideTherapy

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

NameTypeDescriptionInterventions
TherapyExperimentalPatients 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 26, 2016