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

Sponsor

University of Chicago (Other)

Overall Status

Withdrawn

CT.gov ID

NCT02637375

Collaborator

(none)

Enrollment

Arm

Duration (Months)

Study Details

Study Description

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	N/A

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

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

N/A

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 1, 2016

Anticipated Primary Completion Date :

Dec 1, 2018

Anticipated Study Completion Date :

Dec 1, 2018

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Change in GR protein [2 weeks]

Secondary Outcome Measures

Pathological Complete Response (pCR) rate [6 month]
Defined as absence of invasive carcinoma in both the breast and axilla at the time of surgery
Ganetespib toxicity [14 weeks]
Side effects related to Ganetespib as graded per Common Terminology Criteria for Adverse Events (CTCAE) version 4

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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