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

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ClinicalTrials.gov Identifier: NCT02637375
Recruitment Status : Withdrawn (Study never opened (terminated as study drug no longer available))
First Posted : December 22, 2015
Last Update Posted : May 30, 2016
Sponsor:
Information provided by (Responsible Party):
University of Chicago

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.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Ganetespib Drug: Paclitaxel Drug: Doxorubicin Drug: Cyclophosphamide Not Applicable

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Preoperative Trial of Ganetespib With Paclitaxel for Triple-Negative Breast Cancer
Study Start Date : May 2016
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Paclitaxel

Arm Intervention/treatment
Experimental: Therapy
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.
Drug: Ganetespib
Drug: Paclitaxel
Drug: Doxorubicin
Drug: Cyclophosphamide



Primary Outcome Measures :
  1. Change in GR protein [ Time Frame: 2 weeks ]

Secondary Outcome Measures :
  1. Pathological Complete Response (pCR) rate [ Time Frame: 6 month ]
    Defined as absence of invasive carcinoma in both the breast and axilla at the time of surgery

  2. Ganetespib toxicity [ Time Frame: 14 weeks ]
    Side effects related to Ganetespib as graded per Common Terminology Criteria for Adverse Events (CTCAE) version 4



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02637375


Sponsors and Collaborators
University of Chicago
Investigators
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Principal Investigator: Rita Nanda, MD University of Chicago

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Responsible Party: University of Chicago
ClinicalTrials.gov Identifier: NCT02637375     History of Changes
Other Study ID Numbers: IRB15-0848
First Posted: December 22, 2015    Key Record Dates
Last Update Posted: May 30, 2016
Last Verified: May 2016
Keywords provided by University of Chicago:
triple-negative breast cancer
Additional relevant MeSH terms:
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Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Albumin-Bound Paclitaxel
Cyclophosphamide
Doxorubicin
Liposomal doxorubicin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors