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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02637375
• Other study ID #: IRB15-0848
• Status: Withdrawn
• Phase: N/A
• First received: December 17, 2015
• Last updated: May 26, 2016
• Start date: May 2016
• Est. completion date: December 2018

Study information

• Verified date: May 2016
• Source: University of Chicago
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2018
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Triple Negative Breast Neoplasms

Intervention

Drug:
• Ganetespib

• Paclitaxel

• Doxorubicin

• Cyclophosphamide

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University of Chicago

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in GR protein		2 weeks	No
Secondary	Pathological Complete Response (pCR) rate	Defined as absence of invasive carcinoma in both the breast and axilla at the time of surgery	6 month	No
Secondary	Ganetespib toxicity	Side effects related to Ganetespib as graded per Common Terminology Criteria for Adverse Events (CTCAE) version 4	14 weeks	Yes