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Panobinostat and Letrozole in Treating Patients With Metastatic Breast Cancer

Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase II, Phase IBiomarker/Laboratory analysis, TreatmentTemporarily closed18 and overNCI, OtherN093B
NCCTG-N093B, CDR0000669300, NCI-2011-02035, NCT01105312

Trial Description

Summary

RATIONALE: Panobinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Estrogen can cause the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by lowering the amount of estrogen the body makes. Giving panobinostat together with letrozole may be an effective treatment for breast cancer.

PURPOSE: This phase I/II trial is studying the side effects and best dose of panobinostat when given together with letrozole and to see how well it works in treating patients with metastatic breast cancer.

Further Study Information

OBJECTIVES:

Primary Objectives

  • To determine the maximum-tolerated dose of panobinostat in combination with letrozole in patients with metastatic breast cancer. (Phase I)
  • To determine the safety of this regimen in these patients. (Phase I)
  • To assess the confirmed response rate and safety profile of this regimen in patients with triple-negative disease. (Phase II)

Secondary Objectives

  • To assess the therapeutic effects of this regimen in these patients. (Phase I)
  • To examine the duration of response, clinical benefit rate, and time to treatment failure in patients treated with this regimen. (Phase II)
  • To examine the time to progression, progression-free survival, and overall survival of patients treated with this regimen. (Phase II)
  • To examine the estrogen, progesterone, and HER2 status of tumor at primary compared to metastatic tissue, and possibly after treatment. (exploratory)
  • To bank paraffin-embedded tissue blocks/slides and blood products for future studies. (exploratory)
  • To determine expression levels of biomarkers of treatment response (i.e., ER, PR, aromatase, NFkappaB, Ki67, and Caspase 3) in accessible tumors pre- and post-therapy via immunohistochemistry. (exploratory)
  • To determine whether ELISA for KLK11 in serum can be used as marker of activity of letrozole and LBH589. (exploratory) The Phase I portion of this study closed and the Phase II portion of the study opened as per NCCTG Addendum 6, effective January 23, 2012.

OUTLINE: This is a multicenter, phase I dose-escalation study of panobinostat followed by a phase II study. (The Phase I portion of this study closed and the Phase II portion of the study opened as per NCCTG Addendum 6, effective January 23, 2012.)

Patients receive oral panobinostat once daily on days 1, 3, and 5 in weeks 1-4 and oral letrozole once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Tumor tissue and blood samples are collected and banked for future biomarker and other analysis. Samples are also analyzed for biomarkers utilizing immunohistochemistry, microarray, reverse transcription-polymerase chain reaction (RT-PCR), and enzyme-linked immunosorbent assay (ELISA).

After completion of study therapy, patients are followed up every 3-6 months for up to 5 years.

Eligibility Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed breast cancer
  • Metastatic disease amenable to biopsy
  • Unresected tumor with no intention to undergo resection during study
  • Archival tissue from the primary diagnosis or fresh biopsy from metastatic cancer site required
  • Measurable or non-measurable disease for phase I study (The Phase I portion of this study closed and the Phase II portion of the study opened as per NCCTG Addendum 6, effective January 23, 2012.)
  • Measurable disease only for phase II study
  • Available tumor estrogen (ER), progesterone (PR), and HER2 status from metastatic site tested by IHC or FISH OR results from the original tumor diagnosis
  • Any ER, PR, or HER2 level (positive or negative) acceptable (phase I)
  • Triple-negative disease only (phase II)
  • ER and PR negative defined as ≤ 1% by IHC
  • HER2 negative
  • Patients with triple-negative breast cancer allowed provided there is clinical or radiographic evidence of tumor progression in the adjuvant or metastatic setting
  • No patients whose disease can be treated with known standard therapy that is potentially curative or definitely capable of extending life expectancy
  • No known CNS metastasis
  • Hormone-receptor status:
  • ER and PR positive or negative (phase I)
  • ER and PR negative (phase II)

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-1 (phase I) or 0-2 (phase II)
  • Postmenopausal defined by 1 of the following:
  • ≥ 60 years of age
  • ≥ 45 years of age with last menstrual period ≥ 12 months prior and estradiol and follicle-stimulating hormone levels in postmenopausal range
  • Bilateral oophorectomy
  • Life expectancy ≥ 12 weeks
  • ANC ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Total bilirubin normal
  • ALT and AST ≤ 3 times upper limit of normal (ULN) (≤ 5 times ULN if due to liver metastasis)
  • Serum creatinine ≤ 1.5 times ULN
  • TSH normal (thyroid hormone supplements allowed for patients with hypothyroidism)
  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • Willing to return to Mayo Clinic or NCCTG institution (phase II) for follow-up
  • Willing to provide blood samples for correlative research purposes
  • No uncontrolled or intercurrent illness including, but not limited to, any of the following:
  • Ongoing or active infection
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric illness and/or social situations that would limit compliance with study requirements
  • No NYHA class III or IV cardiovascular disease
  • No known seizure disorder
  • No co-morbid systemic illnesses or other severe concurrent disease that, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • No immunocompromised patients, including patients known to be HIV positive
  • Immunocompromised patients due to the use of corticosteroids allowed
  • No malignancy within the past 5 years except for nonmelanoma skin cancer or carcinoma in situ of the cervix
  • No history of myocardial infarction ≤ 6 months
  • No congenital long QT syndrome or QTcF>450 msec, including:
  • Complete left bundle block or use of a permanent cardiac pacemaker, history or presence of ventricular tachyarrhythmias, clinically significant resting bradycardia (<50 beats per minute)
  • Right bundle branch block + left anterior hemiblock (bifascicular block)
  • No congestive heart failure requiring use of maintenance therapy for life-threatening ventricular arrhythmias

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • More than 4 weeks since prior chemotherapy or radiotherapy and fully recovered
  • No radiotherapy to > 25 % of bone marrow
  • Prior treatments allowed (phase II):
  • 0 or 1 prior chemotherapy regimens for breast cancer
  • ≤ 2 prior aromatase-inhibitor regimens (including letrozole)
  • Not currently receiving treatment in a different clinical study in which investigational procedures are performed or investigational therapies are administered
  • No other concurrent investigational agent for the primary neoplasm
  • No concurrent CYP3A4 inhibitors or inducers

Trial Contact Information

Trial Lead Organizations/Sponsors

North Central Cancer Treatment Group

National Cancer Institute

Winston TanPrincipal Investigator

Trial Sites

U.S.A.
Hawaii
  Aiea
 Kapiolani Medical Center at Pali Momi
 William S. Loui Ph: 808-586-2979
  Email: dorothy@crch.hawaii.edu
 William S. Loui Ph: 808-586-2979
  Email: dorothy@crch.hawaii.edu
  Honolulu
 Cancer Research Center of Hawaii
 William S. Loui Ph: 808-586-2979
  Email: dorothy@crch.hawaii.edu
 Kapiolani Medical Center for Women and Children
 William S. Loui Ph: 808-586-2979
  Email: dorothy@crch.hawaii.edu
 Kuakini Medical Center
 William S. Loui Ph: 808-586-2979
  Email: dorothy@crch.hawaii.edu
 OnCare Hawaii, Incorporated - Kuakini
 William S. Loui Ph: 808-586-2979
  Email: dorothy@crch.hawaii.edu
 OnCare Hawaii, Incorporated - Lusitana
 William S. Loui Ph: 808-586-2979
  Email: dorothy@crch.hawaii.edu
 Queen's Cancer Institute at Queen's Medical Center
 William S. Loui Ph: 808-586-2979
  Email: dorothy@crch.hawaii.edu
 Straub Clinic and Hospital, Incorporated
 William S. Loui Ph: 808-586-2979
  Email: dorothy@crch.hawaii.edu
  Kailua
 Castle Medical Center
 William S. Loui Ph: 808-586-2979
  Email: dorothy@crch.hawaii.edu
  Lihue
 Kauai Medical Clinic
 William S. Loui Ph: 808-586-2979
  Email: dorothy@crch.hawaii.edu
Illinois
  Galesburg
 Galesburg Clinic, PC
 Nguyet A Le-Lindqwister Ph: 800-793-2262
Michigan
  Flint
 Genesys Hurley Cancer Institute
 Christopher M Reynolds Ph: 734-712-3456
North Dakota
  Bismarck
 Bismarck Cancer Center
 Edward J. Wos Ph: 701-323-5760
  Email: tfischer@mohs.org
Oklahoma
  Norman
 Cancer Care Associates - Norman
 Vikki Ann Canfield Ph: 888-823-5923
  Email: ctsucontact@westat.com
  Oklahoma City
 Cancer Care Associates - Mercy Campus
 Vikki Ann Canfield Ph: 888-823-5923
  Email: ctsucontact@westat.com

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01105312
ClinicalTrials.gov processed this data on October 17, 2013

Note: Information about this trial is from the ClinicalTrials.gov database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the ClinicalTrials.gov record to standardize the names of study sponsors, sites, and contacts. Cancer.gov only lists sites that are recruiting patients for active trials, whereas ClinicalTrials.gov lists all sites for all trials. Questions and comments regarding the presented information should be directed to ClinicalTrials.gov.

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