Carboplatin and Paclitaxel Albumin-Stabilized Nanoparticle Formulation With or Without Vorinostat in Treating Women With Breast Cancer That Can Be Removed by Surgery

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00616967
First received: February 14, 2008
Last updated: March 18, 2013
Last verified: March 2013
  Purpose

RATIONALE: Drugs used in chemotherapy, such as carboplatin and paclitaxel albumin-stabilized nanoparticle formulation, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Vorinostat may also help carboplatin and paclitaxel albumin-stabilized nanoparticle formulation work better by making tumor cells more sensitive to the drugs. Giving chemotherapy with or without vorinostat before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This randomized phase II trial is studying how well giving carboplatin together with paclitaxel albumin-stabilized nanoparticle formulation works with or without vorinostat in treating women with breast cancer that can be removed by surgery.


Condition Intervention Phase
Breast Cancer
Drug: carboplatin
Drug: paclitaxel albumin-stabilized nanoparticle formulation
Drug: vorinostat
Other: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multi-Institutional Double-Blind Phase II Study Evaluating Response and Surrogate Biomarkers to Carboplatin and Nab-Paclitaxel (CP) With or Without Vorinostat as Preoperative Chemotherapy in HER2-negative Primary Operable Breast Cancer

Resource links provided by NLM:


Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures:
  • Pathological complete response (pCR) rate [ Time Frame: Time of breast cancer surgery ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety as measured by NCI CTCAE version 3.0 [ Time Frame: Active treatment until 30 days post-treatment ] [ Designated as safety issue: Yes ]
  • Clinical complete response (cCR) rate [ Time Frame: Time of breast cancer surgery ] [ Designated as safety issue: No ]
  • Standard uptake values as measured by baseline and changes (day 15) on FDG-PET [ Time Frame: Baseline and day 15 ] [ Designated as safety issue: No ]
  • Baseline and change in markers of apoptosis and proliferation [ Time Frame: Time of breast cancer surgery ] [ Designated as safety issue: No ]
  • Long term outcomes [ Time Frame: Indefinite survival analysis ] [ Designated as safety issue: No ]
  • Baseline and change in continuous variables (e.g., candidate gene methylation, expression profiles, tissue, and peripheral blood mononuclear cell histone acetylation) [ Time Frame: Time of breast cancer surgery ] [ Designated as safety issue: No ]

Estimated Enrollment: 74
Study Start Date: May 2008
Estimated Study Completion Date: June 2017
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I
Patients receive carboplatin IV and paclitaxel albumin-stabilized nanoparticle formulation IV on day 1 and an oral placebo on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.
Drug: carboplatin
Given IV
Other Name: Paraplatin
Drug: paclitaxel albumin-stabilized nanoparticle formulation
Given IV
Other Name: Abraxane, nab-Paclitaxel
Other: placebo
Given orally
Experimental: Arm II
Patients receive carboplatin and paclitaxel albumin-stabilized nanoparticle formulation as in arm I and oral vorinostat on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.
Drug: carboplatin
Given IV
Other Name: Paraplatin
Drug: paclitaxel albumin-stabilized nanoparticle formulation
Given IV
Other Name: Abraxane, nab-Paclitaxel
Drug: vorinostat
Given orally
Other Name: Zolinza

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00616967

Locations
United States, Indiana
Indiana University Purdue University of Indianapolis
Indianapolis, Indiana, United States, 46202
United States, Maryland
Anne Arundel Health System
Annapolis, Maryland, United States, 21401
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
United States, Minnesota
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
Investigators
Study Chair: Vered Stearns, MD Sidney Kimmel Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00616967     History of Changes
Other Study ID Numbers: JHOC-J0785, CDR0000586335, P30CA006973, JHOC-SKCCC-J0785
Study First Received: February 14, 2008
Last Updated: March 18, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
ductal breast carcinoma
lobular breast carcinoma

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Vorinostat
Carboplatin
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic
Histone Deacetylase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on April 20, 2014