Study on Carboplatin and Nab-Paclitaxel With or Without Vorinostat for Treating Women with Newly Diagnosed Operable Breast Cancer

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Sponsor score: 60

ClinicalTrials ID:NCT00616967

Provider View

This clinical trial is testing whether adding the drug vorinostat to standard chemotherapy can help shrink breast tumors before surgery. The study aims to see if this combination is more effective than chemotherapy alone in women with operable breast cancer.

Patient Parameters

Program Overview

The purpose of this study is to find out if adding the drug vorinostat to standard chemotherapy drugs, carboplatin and nab-paclitaxel, can help shrink breast tumors before surgery. Vorinostat may make cancer cells more sensitive to chemotherapy, potentially reducing the size of the tumor and the amount of normal tissue that needs to be removed during surgery. This trial will compare the effectiveness of chemotherapy with and without vorinostat in women with breast cancer that can be surgically removed.

Description

This study is divided into two main parts: a preliminary safety phase and the main study phase.

In the preliminary phase, a small group of patients will receive chemotherapy drugs carboplatin and nab-paclitaxel, along with vorinostat, to ensure the combination is safe. If this phase is successful, more patients will be enrolled in the main study phase.

In the main study phase, participants will be randomly assigned to one of two groups:

  • Group 1 will receive chemotherapy with carboplatin and nab-paclitaxel, along with a placebo (a pill with no active drug).
  • Group 2 will receive the same chemotherapy drugs, but with the addition of vorinostat.

Both groups will receive treatment once a week for 12 weeks, unless the cancer progresses or side effects become too severe. After completing the treatment, patients will have surgery to remove the tumor.

Throughout the study, researchers will collect tumor tissue and blood samples to analyze how the treatment affects cancer cells and to identify any markers that might predict how well the treatment works. Patients will also undergo imaging tests to monitor how the tumor responds to the treatment.

After the study treatment is completed, patients will have follow-up visits every six months to monitor their health and check for any signs of cancer returning.

Eligibility Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed infiltrating ductal breast cancer by core needle biopsy

    • Mixed ductal and lobular disease allowed
    • Infiltrating lobular cancer allowed in the run-in portion only

  • Unresected, clinically measurable disease, meeting 1 of the following clinical staging criteria:

    • T2, T3, or T4 lesion, any N, M0
    • T1c, N1-3,M0

  • Patients with skin metastases to the ipsilateral breast for whom chemotherapy is planned prior to definitive surgery are eligible for the primary study portion

  • HER2-negative disease

  • Hormone receptor status* meeting 1 of the following criteria:

    • Estrogen receptor (ER)-negative and progesterone receptor (PR)-negative
    • ER-positive (grade II or III) and PR-positive or PR-negative NOTE: *Any ER or PR status for the run-in portion

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-1
  • Menopausal status not specified
  • ANC ≥ 1,500/mm³
  • Platelet count ≥ 150,000/mm³
  • Hemoglobin ≥ 9 g/dL
  • Creatinine ≤ 1.5 times the upper limit of normal (ULN)
  • Creatinine clearance ≥ 50 mL/min
  • Total bilirubin normal
  • AST(SGOT) and ALT(SGPT) ≤ 2.5 times (ULN)
  • alkaline phosphatase ≤ 2.5 times ULN
  • PT such that INR ≤ 1.5 (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin) and PTT ≤ ULN
  • Adequate cardiac function defined as no evidence of PR prolongation or AV block on baseline electrocardiogram (ECG)
  • Willing to use effective, non-hormonal contraception while on treatment and for at least 3 months thereafter
  • Not pregnant or nursing
  • No pre-existing peripheral neuropathy ≥ grade 2
  • No history of severe hypersensitivity reaction to any drug formulated with polysorbate 80 or to E. coli-derived products
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat
  • No medical condition which, in the opinion of the investigator, puts the patient at risk of potentially serious complications while on this therapy

PRIOR CONCURRENT THERAPY:

  • At least 4 weeks since prior valproic acid or other histone deacetylase inhibitor

  • No prior chemotherapy, radiotherapy, or endocrine therapy for this cancer

    • Prior tamoxifen or raloxifene or another agent for prevention of breast cancer allowed as long as the patient has discontinued the treatment ≥ 1 month prior to baseline study biopsy

  • No systemic treatment for prior cancer within the past 5 years (primary study portion)

  • No prior or ongoing systemic treatment for this cancer (primary study portion)

  • No concurrent combination antiretroviral therapy for HIV-positive patients

  • No other concurrent histone deacetylase inhibitor

  • No other concurrent chemotherapy, antiestrogen therapy, radiotherapy, or other investigational systemic therapy

  • No other concurrent biologic therapy

  • No other concurrent investigational drugs

Locations

FACILITYZIPCITYSTATE
University of Alabama Comprehensive Cancer Center35249BirminghamAlabama
Indiana University Purdue University of Indianapolis46202IndianapolisIndiana
Anne Arundel Health System21401AnnapolisMaryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins21231-2410BaltimoreMaryland
Mayo Clinic Cancer Center55905RochesterMinnesota

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