Know Cancer

forgot password

Phase I/II Study of Panobinostat (LBH589) and Letrozole in Patients With Triple Negative Metastatic Breast Cancer

Phase 1/Phase 2
18 Years
Open (Enrolling)
Breast Cancer

Thank you

Trial Information

Phase I/II Study of Panobinostat (LBH589) and Letrozole in Patients With Triple Negative Metastatic Breast Cancer


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.

- 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,

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

Inclusion Criteria


- 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)


- 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

- 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

- 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


- 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

- No other concurrent investigational agent for the primary neoplasm

- No concurrent CYP3A4 inhibitors or inducers

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum-tolerated dose (phase I)

Safety Issue:


Principal Investigator

Winston Tan, MD, FACP

Investigator Role:

Principal Investigator

Investigator Affiliation:

Mayo Clinic



Study ID:




Start Date:

September 2010

Completion Date:

Related Keywords:

  • Breast Cancer
  • male breast cancer
  • estrogen receptor-negative breast cancer
  • estrogen receptor-positive breast cancer
  • HER2-negative breast cancer
  • HER2-positive breast cancer
  • progesterone receptor-negative breast cancer
  • progesterone receptor-positive breast cancer
  • triple-negative breast cancer
  • recurrent breast cancer
  • stage IV breast cancer
  • Breast Neoplasms



Mayo Clinic Scottsdale Scottsdale, Arizona  85259
Mayo Clinic - Jacksonville Jacksonville, Florida  32224
Mayo Clinic Cancer Center Rochester, Minnesota  55905
CCOP - Wichita Wichita, Kansas  67214-3882
Hurley Medical Center Flint, Michigan  48503
CCOP - Missouri Valley Cancer Consortium Omaha, Nebraska  68131
CCOP - Mount Sinai Medical Center Miami Beach, Florida  33140
CCOP - Illinois Oncology Research Association Peoria, Illinois  61602
Aurora Presbyterian Hospital Aurora, Colorado  80012
Boulder Community Hospital Boulder, Colorado  80301-9019
Penrose Cancer Center at Penrose Hospital Colorado Springs, Colorado  80933
Porter Adventist Hospital Denver, Colorado  80210
Presbyterian - St. Luke's Medical Center Denver, Colorado  80218
St. Joseph Hospital Denver, Colorado  80218
Rose Medical Center Denver, Colorado  80220
Swedish Medical Center Englewood, Colorado  80110
Sky Ridge Medical Center Lone Tree, Colorado  80124
Hope Cancer Care Center at Longmont United Hospital Longmont, Colorado  80502
St. Mary - Corwin Regional Medical Center Pueblo, Colorado  81004
North Suburban Medical Center Thornton, Colorado  80229
CCOP - Michigan Cancer Research Consortium Ann Arbor, Michigan  48106
Saint Joseph Mercy Cancer Center Ann Arbor, Michigan  48106-0995
Oakwood Cancer Center at Oakwood Hospital and Medical Center Dearborn, Michigan  48123-2500
Genesys Hurley Cancer Institute Flint, Michigan  48503
Van Elslander Cancer Center at St. John Hospital and Medical Center Grosse Pointe Woods, Michigan  48236
Sparrow Regional Cancer Center Lansing, Michigan  48912-1811
St. John Macomb Hospital Warren, Michigan  48093
Natalie Warren Bryant Cancer Center at St. Francis Hospital Tulsa, Oklahoma  74136
Geisinger Medical Group - Scenery Park State College, Pennsylvania  16801
Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center Wilkes-Barre, Pennsylvania  18711
CCOP - Bay Area Tumor Institute Oakland, California  94609-3305
Methodist Medical Center of Illinois Peoria, Illinois  61636
Ellis Fischel Cancer Center at University of Missouri - Columbia Columbia, Missouri  65203
Cancer Research Center of Hawaii Honolulu, Hawaii  96813
Peninsula Regional Medical Center Salisbury, Maryland  21801
Louis A. Weiss Memorial Hospital Chicago, Illinois  60640
St. Vincent Mercy Medical Center Toledo, Ohio  43608
Long Island Jewish Medical Center New Hyde Park, New York  11040
Via Christi Cancer Center at Via Christi Regional Medical Center Wichita, Kansas  67214
Alvin and Lois Lapidus Cancer Institute at Sinai Hospital Baltimore, Maryland  21215
Presbyterian Cancer Center at Presbyterian Hospital Charlotte, North Carolina  28233-3549
Wake Forest University Comprehensive Cancer Center Winston-Salem, North Carolina  27157-1096
Medical University of Ohio Cancer Center Toledo, Ohio  43614
Toledo Hospital Toledo, Ohio  43606
St. Vincent Hospital Regional Cancer Center Green Bay, Wisconsin  54307-3508
CCOP - Hematology-Oncology Associates of Central New York East Syracuse, New York  13057
St. Mary's Hospital Medical Center - Green Bay Green Bay, Wisconsin  54303
Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center Green Bay, Wisconsin  54301-3526
Green Bay Oncology, Limited at St. Mary's Hospital Green Bay, Wisconsin  54303
Bay Area Cancer Care Center at Bay Area Medical Center Marinette, Wisconsin  54143
North Colorado Medical Center Greeley, Colorado  80631
McKee Medical Center Loveland, Colorado  80539
Wayne Memorial Hospital, Incorporated Goldsboro, North Carolina  27534
Memorial Cancer Institute at Memorial Regional Hospital Hollywood, Florida  33021
New York Weill Cornell Cancer Center at Cornell University New York, New York  10021
Don Monti Comprehensive Cancer Center at North Shore University Hospital Manhasset, New York  11030
Oklahoma University Cancer Institute Oklahoma City, Oklahoma  73104
Geisinger Cancer Institute at Geisinger Health Danville, Pennsylvania  17822-0001
Gundersen Lutheran Center for Cancer and Blood La Crosse, Wisconsin  54601
Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center Hartford, Connecticut  06105
Front Range Cancer Specialists Fort Collins, Colorado  80528
Poudre Valley Hospital Fort Collins, Colorado  80524
Ella Milbank Foshay Cancer Center at Jupiter Medical Center Jupiter, Florida  33458
Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center Boise, Idaho  83706
St. Joseph Medical Center Bloomington, Illinois  61701
Eureka Community Hospital Eureka, Illinois  61530
BroMenn Regional Medical Center Normal, Illinois  61761
Community Cancer Center Normal, Illinois  61761
Community Hospital of Ottawa Ottawa, Illinois  61350
Oncology Hematology Associates of Central Illinois, PC - Ottawa Ottawa, Illinois  61350
Cancer Treatment Center at Pekin Hospital Pekin, Illinois  61554
Oncology Hematology Associates of Central Illinois, PC - Peoria Peoria, Illinois  61615
OSF St. Francis Medical Center Peoria, Illinois  61637
Proctor Hospital Peoria, Illinois  61614
Illinois Valley Community Hospital Peru, Illinois  61354
Cancer Center of Kansas, PA - Dodge City Dodge City, Kansas  67801
Hickman Cancer Center at Bixby Medical Center Adrian, Michigan  49221
Community Cancer Center of Monroe Monroe, Michigan  48162
Immanuel Medical Center Omaha, Nebraska  68122
Creighton University Medical Center Omaha, Nebraska  68131-2197
Wood County Oncology Center Bowling Green, Ohio  43402
Lima Memorial Hospital Lima, Ohio  45804
Northwest Ohio Oncology Center Maumee, Ohio  43537
Toledo Clinic - Oregon Oregon, Ohio  43616
St. Charles Mercy Hospital Oregon, Ohio  43616
Mercy Hospital of Tiffin Tiffin, Ohio  44883
Toledo Clinic, Incorporated - Main Clinic Toledo, Ohio  43623
Fulton County Health Center Wauseon, Ohio  43567
Oncology Services of Aberdeen Aberdeen, South Dakota  57401
Danville Regional Medical Center Danville, Virginia  24541
Holy Family Memorial Medical Center Cancer Care Center Manitowoc, Wisconsin  54221-1450
St. Anthony Central Hospital Denver, Colorado  80204-1335
Exempla Lutheran Medical Center Wheat Ridge, Colorado  80033
Cancer Resource Center - Lincoln Lincoln, Nebraska  68510
Randolph Hospital Asheboro, North Carolina  27203
Moses Cone Regional Cancer Center at Wesley Long Community Hospital Greensboro, North Carolina  27401
Annie Penn Cancer Center Reidsville, North Carolina  27320
Altru Cancer Center at Altru Hospital Grand Forks, North Dakota  58201
Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital Fort Lauderdale, Florida  33308
John B. Amos Cancer Center Columbus, Georgia  31904
McFarland Clinic, PC Ames, Iowa  50010
Cancer Center of Kansas, PA - Chanute Chanute, Kansas  66720
Cancer Center of Kansas, PA - El Dorado El Dorado, Kansas  67042
Cancer Center of Kansas - Fort Scott Fort Scott, Kansas  66701
Cancer Center of Kansas-Independence Independence, Kansas  67301
Cancer Center of Kansas, PA - Kingman Kingman, Kansas  67068
Lawrence Memorial Hospital Lawrence, Kansas  66044
Cancer Center of Kansas, PA - Liberal Liberal, Kansas  67905
Cancer Center of Kansas, PA - Newton Newton, Kansas  67114
Cancer Center of Kansas, PA - Parsons Parsons, Kansas  67357
Cancer Center of Kansas, PA - Pratt Pratt, Kansas  67124
Cancer Center of Kansas, PA - Salina Salina, Kansas  67401
Cancer Center of Kansas, PA - Wellington Wellington, Kansas  67152
Cancer Center of Kansas, PA - Wichita Wichita, Kansas  67214
Associates in Womens Health, PA - North Review Wichita, Kansas  67208
Cancer Center of Kansas, PA - Medical Arts Tower Wichita, Kansas  67208
Cancer Center of Kansas, PA - Winfield Winfield, Kansas  67156
Foote Memorial Hospital Jackson, Michigan  49201
St. Mary Mercy Hospital Livonia, Michigan  48154
Mercy Memorial Hospital - Monroe Monroe, Michigan  48162
St. Joseph Mercy Oakland Pontiac, Michigan  48341-2985
Mercy Regional Cancer Center at Mercy Hospital Port Huron, Michigan  48060
Seton Cancer Institute at Saint Mary's - Saginaw Saginaw, Michigan  48601
Alegant Health Cancer Center at Bergan Mercy Medical Center Omaha, Nebraska  68124
Monter Cancer Center of the North Shore-LIJ Health System Lake Success, New York  11042
Hematology Oncology Center Elyria, Ohio  44035
Community Cancer Center Elyria, Ohio  44035
Flower Hospital Cancer Center Sylvania, Ohio  43560
St. Anne Mercy Hospital Toledo, Ohio  43623
Geisinger Hazleton Cancer Center Hazleton, Pennsylvania  18201
Fredericksburg Oncology, Incorporated Fredericksburg, Virginia  22401
Mid Dakota Clinic, PC Bismarck, North Dakota  58501
Queen's Cancer Institute at Queen's Medical Center Honolulu, Hawaii  96813
Pardee Memorial Hospital Hendersonville, North Carolina  28791
Kinston Medical Specialists Kinston, North Carolina  28501
Resurrection Medical Center Chicago, Illinois  60631
Doctors Medical Center - San Pablo Campus San Pablo, California  94806
Galesburg Clinic, PC Galesburg, Illinois  61401
Contra Costa Regional Medical Center Martinez, California  94553-3156
El Camino Hospital Cancer Center Mountain View, California  94040
Larry G Strieff MD Medical Corporation Oakland, California  94609
Tom K Lee, Incorporated Oakland, California  94609
Bay Area Breast Surgeons, Incorporated Oakland, California  94609
Kapiolani Medical Center at Pali Momi Aiea, Hawaii  96701
Kapiolani Medical Center for Women and Children Honolulu, Hawaii  96826
Straub Clinic and Hospital, Incorporated Honolulu, Hawaii  96813
OnCare Hawaii, Incorporated - Kuakini Honolulu, Hawaii  96817
OnCare Hawaii, Incorporated - Lusitana Honolulu, Hawaii  96813
Illinois CancerCare - Bloomington Bloomington%, Illinois  61701
Illinois CancerCare - Canton Canton, Illinois  61520
Illinois CancerCare - Carthage Carthage, Illinois  62321
Illinois CancerCare - Eureka Eureka, Illinois  61530
Illinois CancerCare - Havana Havana, Illinois  62644
Illinois CancerCare - Kewanee Clinic Kewanee, Illinois  61443
Illinois CancerCare - Macomb Macomb, Illinois  61455
OSF Holy Family Medical Center Monmouth, Illinois  61462
Illinois CancerCare - Monmouth Monmouth, Illinois  61462
Illinois CancerCare - Community Cancer Center Normal, Illinois  61761
Illinois CancerCare - Pekin Pekin, Illinois  61603
Illinois CancerCare - Peru Peru, Illinois  61354
Illinois CancerCare - Princeton Princeton, Illinois  61356
Illinois CancerCare - Spring Valley Spring Valley, Illinois  61362
Fountain Valley, California  92708
Medcenter One Hospital Cancer Care Center Bismarck, North Dakota  58501
St. Alexius Medical Center Cancer Center Bismarck, North Dakota  58502
Florida Hospital Memorial Medical Center Daytona Beach, Florida  32117
Castle Medical Center Kailua, Hawaii  96734
Kauai Medical Clinic Lihue, Hawaii  96766
Lakeside Hospital Omaha, Nebraska  68130
St. Nicholas Hospital Sheboygan, Wisconsin  53081
Kuakini Medical Center Honolulu, Hawaii  96817
Oncare Hawaii, Incorporated - Pali Momi Aiea, Hawaii  96701