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Vorinostat, Paclitaxel, and Bevacizumab in Treating Patients With Metastatic Breast Cancer and/or Breast Cancer That Has Recurred in the Chest Wall and Cannot be Removed by Surgery
This study is ongoing, but not recruiting participants.
First Received: August 24, 2006   Last Updated: April 14, 2009   History of Changes
Sponsors and Collaborators: Albert Einstein College of Medicine of Yeshiva University
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00368875
  Purpose

RATIONALE: Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some find tumor cells and kill them or carry tumor-killing substances to them.

Others interfere with the ability of tumor cells to grow and spread. Bevacizumab may also may stop the growth of tumor cells by blocking blood flow to the tumor. Giving vorinostat together with paclitaxel and bevacizumab may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of vorinostat when given together with paclitaxel and bevacizumab and to see how well they work in treating patients with metastatic breast cancer and/or breast cancer that has recurred in the chest wall and cannot be removed by surgery.


Condition Intervention Phase
Breast Cancer
Biological: bevacizumab
Drug: paclitaxel
Drug: vorinostat
Phase I
Phase II

Study Type: Interventional
Study Design: Treatment, Open Label
Official Title: A Phase I/II Study of a Combination of Suberoylanilide Hydroxamic Acid (Vorinostat) Plus Paclitaxel and Bevacizumab in Patients With Advanced Metastatic and/or Local Chest Wall Recurrent Breast Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Maximum tolerated dose of vorinostat in combination with paclitaxel and bevacizumab [ Designated as safety issue: Yes ]
  • Recommended phase II dose [ Designated as safety issue: Yes ]
  • Objective response rate (complete and partial) [ Designated as safety issue: No ]
  • Overall-survival by Kaplan-Meier survival analysis [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to treatment failure by Kaplan-Meier survival analysis [ Designated as safety issue: No ]
  • Progression-free survival by Kaplan-Meier survival analysis [ Designated as safety issue: No ]
  • Toxicity according to CTCAE v. 3.0 [ Designated as safety issue: Yes ]

Estimated Enrollment: 45
Study Start Date: July 2006
Estimated Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • Determine the maximum tolerated dose and recommended phase II dose of vorinostat (SAHA) in combination with paclitaxel and bevacizumab in patients with metastatic and/or locally recurrent inoperable chest wall breast cancer. (Phase I)
  • Determine the efficacy (i.e., response rate, response duration, time to disease progression, time to treatment failure, and overall survival) of this regimen in these patients. (Phase II)
  • Determine the toxicity of this regimen in these patients. (Phase II)

OUTLINE: This is a phase I, multicenter, dose-escalation study of vorinostat (SAHA) followed by a phase II, open-label study.

  • Phase I: Patients receive oral SAHA twice daily on days 1-3, 8-10, and 15-17, paclitaxel IV over 1 hour on days 2, 9, and 16, and bevacizumab IV over 30-90 minutes on days 2 and 16. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of SAHA until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. The recommended phase II dose is defined as one dose level below the MTD.
  • Phase II: Patients receive SAHA at the recommended phase II dose and paclitaxel and bevacizumab as in phase I.

PROJECTED ACCRUAL: Approximately 45 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed adenocarcinoma of the breast, meeting ≥ 1 of the following criteria:

    • Stage IV disease
    • Locally recurrent inoperable chest wall disease
  • At least 1 unidimensionally or bidimesionally measurable indicator lesion

    • Nonmeasurable disease allowed (phase I only)
  • No CNS metastases by CT scan or MRI
  • Hormone receptor status not specified

PATIENT CHARACTERISTICS:

  • Female or male
  • Menopausal status not specified
  • ECOG performance status (PS) 0-1 or Karnofsky PS 70-100%
  • Absolute neutrophil count ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Bilirubin normal
  • AST and ALT ≤ 2.5 times upper limit of normal (ULN)
  • PTT < 1.5 times normal
  • INR or PT < 1.5 times normal (unless patient is on full-dose anticoagulants)
  • Creatinine normal OR creatinine clearance ≥ 60 mL/min
  • Urine:protein creatinine ratio ≤ 0.5 OR urine protein < 1,000 mg by 24-hour urine collection
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for ≥ 6 months after completion of study therapy
  • Must be able to take oral medications on a continuous basis
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to study drugs
  • No ongoing or active infection
  • No psychiatric illness or social situation that would limit study compliance
  • No serious or nonhealing wound, ulcer, or bone fracture
  • No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 4 weeks
  • No significant traumatic injury within the past 4 weeks
  • No clinically significant cardiovascular disease, including any of the following:

    • Cerebrovascular accident within the past 6 months
    • Unstable angina pectoris
    • Uncontrolled hypertension
    • Myocardial infarction or unstable angina within the past 6 months
    • New York Heart Association class II-IV congestive heart failure
    • Serious cardiac arrhythmia requiring medication
    • Symptomatic congestive heart failure
    • Clinically significant peripheral vascular disease
  • No bleeding diathesis or coagulopathy
  • No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
  • No other uncontrolled illness

PRIOR CONCURRENT THERAPY:

  • At least 1 week since prior hormonal therapy

    • Any number of prior hormonal therapies allowed
  • At least 1 week since prior core biopsy
  • At least 10 days since prior acetylsalicylic acid (aspirin > 325 mg/day) or other nonsteroidal anti-inflammatory drugs known to inhibit platelet function, including any of the following:

    • Dipyridamole
    • Ticlopidine
    • Clopidogrel
    • Cilostazol
  • At least 4 weeks since prior major surgical procedure or open biopsy
  • At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) or radiotherapy and recovered
  • At least 4 weeks since prior trastuzumab (Herceptin®)
  • No prior chemotherapy for metastatic disease

    • Patients previously treated with a taxane (e.g., docetaxel or paclitaxel) are eligible provided both of the following are true:

      • Received taxane as a component of adjuvant and/or neoadjuvant therapy
      • Relapsed ≥ 12 months after completion of taxane-based therapy
  • No prior histone deacetylase inhibitors (e.g., valproic acid, PXD101, FR901228, MS-275, or LAQ-824)

    • Patients who have received such agents for other indications (e.g., epilepsy) may enroll in this trial after a 30-day washout period
  • No prior bevacizumab
  • No prior gastrointestinal surgery or other procedures that may interfere with absorption or swallowing of study drug
  • No other prior invasive procedures
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No other concurrent investigational agents
  • No other concurrent anticancer agents or therapies
  • No other concurrent investigational agents
  • No concurrent major surgical procedures
  • Concurrent full-dose anticoagulants (e.g., warfarin) with PT INR > 1.5 allowed provided both of the following criteria are met:

    • In-range INR (usually between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin
    • No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00368875

  Show 24 Study Locations
Sponsors and Collaborators
Albert Einstein College of Medicine of Yeshiva University
Investigators
Study Chair: Joseph A. Sparano, MD Albert Einstein College of Medicine of Yeshiva University
  More Information

Additional Information:
No publications provided

Responsible Party: Albert Einstein Cancer Center at Albert Einstein College of Medicine ( Joseph A. Sparano )
Study ID Numbers: CDR0000495242, AECM-0605291, NCI-7703
Study First Received: August 24, 2006
Last Updated: April 14, 2009
ClinicalTrials.gov Identifier: NCT00368875     History of Changes
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
stage IV breast cancer
recurrent breast cancer
male breast cancer
stage IIIB breast cancer
stage IIIC breast cancer

Study placed in the following topic categories:
Anticarcinogenic Agents
Anti-Inflammatory Agents
Skin Diseases
Vorinostat
Breast Neoplasms
Breast Cancer, Male
Bevacizumab
Antimitotic Agents
Angiogenesis Inhibitors
Recurrence
Breast Neoplasms, Male
Analgesics, Non-Narcotic
Paclitaxel
Tubulin Modulators
Anti-Inflammatory Agents, Non-Steroidal
Peripheral Nervous System Agents
Analgesics
Antirheumatic Agents
Antineoplastic Agents, Phytogenic
Breast Diseases

Additional relevant MeSH terms:
Anticarcinogenic Agents
Anti-Inflammatory Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Bevacizumab
Neoplasms by Site
Sensory System Agents
Therapeutic Uses
Anti-Inflammatory Agents, Non-Steroidal
Growth Inhibitors
Angiogenesis Modulating Agents
Analgesics
Breast Diseases
Skin Diseases
Growth Substances
Mitosis Modulators
Vorinostat
Breast Neoplasms
Enzyme Inhibitors
Antimitotic Agents
Angiogenesis Inhibitors
Protective Agents
Pharmacologic Actions
Neoplasms
Paclitaxel
Analgesics, Non-Narcotic
Tubulin Modulators
Peripheral Nervous System Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on August 12, 2009