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

NCT02637375 | Withdrawn

• 1 other identifier: IRB15-0848
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Breast Cancer

Keywords

triple-negative breast cancer

Outcome Measures

Primary Outcomes (1)

• Change in GR protein

  2 weeks

Secondary Outcomes (2)

• Pathological Complete Response (pCR) rate

  6 month

• Ganetespib toxicity

  14 weeks

Study Arms (1)

Therapy

EXPERIMENTAL

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

Interventions

Ganetespib DRUG

Therapy

Paclitaxel DRUG

Therapy

Doxorubicin DRUG

Therapy

Cyclophosphamide DRUG

Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Chicago: lead

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

STA 9090; Paclitaxel; Doxorubicin; Cyclophosphamide

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds

Study Officials

• Rita Nanda, MD

  University of Chicago

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2015
• First Posted: December 22, 2015
• Study Start: May 1, 2016
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2018
• Last Updated: May 30, 2016

Record last verified: 2016-05