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

NCT ID: NCT02637375

Last Updated: 2016-05-30

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: NA
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-31
• Study Completion Date: 2018-12-31

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

Conditions

Breast Cancer

Keywords

triple-negative breast cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Ganetespib

Intervention Type: DRUG

Paclitaxel

Intervention Type: DRUG

Doxorubicin

Intervention Type: DRUG

Cyclophosphamide

Intervention Type: DRUG

Interventions

Ganetespib

Intervention Type: DRUG

Paclitaxel

Intervention Type: DRUG

Doxorubicin

Intervention Type: DRUG

Cyclophosphamide

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University of Chicago

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rita Nanda, MD

Role: PRINCIPAL_INVESTIGATOR

University of Chicago

Countries

United States

Other Identifiers

IRB15-0848

Identifier Type: -

Identifier Source: org_study_id