Know Cancer

or
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
N/A
Open (Enrolling)
Both
Breast Cancer

Thank you

Trial Information

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


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum-tolerated dose (phase I)

Safety Issue:

Yes

Principal Investigator

Winston Tan, MD, FACP

Investigator Role:

Principal Investigator

Investigator Affiliation:

Mayo Clinic

Authority:

Unspecified

Study ID:

CDR0000669300

NCT ID:

NCT01105312

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

Name

Location

Mayo Clinic ScottsdaleScottsdale, Arizona  85259
Mayo Clinic - JacksonvilleJacksonville, Florida  32224
Mayo Clinic Cancer CenterRochester, Minnesota  55905
CCOP - WichitaWichita, Kansas  67214-3882
Hurley Medical CenterFlint, Michigan  48503
CCOP - Missouri Valley Cancer ConsortiumOmaha, Nebraska  68131
CCOP - Mount Sinai Medical CenterMiami Beach, Florida  33140
CCOP - Illinois Oncology Research AssociationPeoria, Illinois  61602
Aurora Presbyterian HospitalAurora, Colorado  80012
Boulder Community HospitalBoulder, Colorado  80301-9019
Penrose Cancer Center at Penrose HospitalColorado Springs, Colorado  80933
Porter Adventist HospitalDenver, Colorado  80210
Presbyterian - St. Luke's Medical CenterDenver, Colorado  80218
St. Joseph HospitalDenver, Colorado  80218
Rose Medical CenterDenver, Colorado  80220
Swedish Medical CenterEnglewood, Colorado  80110
Sky Ridge Medical CenterLone Tree, Colorado  80124
Hope Cancer Care Center at Longmont United HospitalLongmont, Colorado  80502
St. Mary - Corwin Regional Medical CenterPueblo, Colorado  81004
North Suburban Medical CenterThornton, Colorado  80229
CCOP - Michigan Cancer Research ConsortiumAnn Arbor, Michigan  48106
Saint Joseph Mercy Cancer CenterAnn Arbor, Michigan  48106-0995
Oakwood Cancer Center at Oakwood Hospital and Medical CenterDearborn, Michigan  48123-2500
Genesys Hurley Cancer InstituteFlint, Michigan  48503
Van Elslander Cancer Center at St. John Hospital and Medical CenterGrosse Pointe Woods, Michigan  48236
Sparrow Regional Cancer CenterLansing, Michigan  48912-1811
St. John Macomb HospitalWarren, Michigan  48093
Natalie Warren Bryant Cancer Center at St. Francis HospitalTulsa, Oklahoma  74136
Geisinger Medical Group - Scenery ParkState College, Pennsylvania  16801
Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical CenterWilkes-Barre, Pennsylvania  18711
CCOP - Bay Area Tumor InstituteOakland, California  94609-3305
Methodist Medical Center of IllinoisPeoria, Illinois  61636
Ellis Fischel Cancer Center at University of Missouri - ColumbiaColumbia, Missouri  65203
Cancer Research Center of HawaiiHonolulu, Hawaii  96813
Peninsula Regional Medical CenterSalisbury, Maryland  21801
Louis A. Weiss Memorial HospitalChicago, Illinois  60640
St. Vincent Mercy Medical CenterToledo, Ohio  43608
Long Island Jewish Medical CenterNew Hyde Park, New York  11040
Via Christi Cancer Center at Via Christi Regional Medical CenterWichita, Kansas  67214
Alvin and Lois Lapidus Cancer Institute at Sinai HospitalBaltimore, Maryland  21215
Presbyterian Cancer Center at Presbyterian HospitalCharlotte, North Carolina  28233-3549
Wake Forest University Comprehensive Cancer CenterWinston-Salem, North Carolina  27157-1096
Medical University of Ohio Cancer CenterToledo, Ohio  43614
Toledo HospitalToledo, Ohio  43606
St. Vincent Hospital Regional Cancer CenterGreen Bay, Wisconsin  54307-3508
CCOP - Hematology-Oncology Associates of Central New YorkEast Syracuse, New York  13057
St. Mary's Hospital Medical Center - Green BayGreen Bay, Wisconsin  54303
Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer CenterGreen Bay, Wisconsin  54301-3526
Green Bay Oncology, Limited at St. Mary's HospitalGreen Bay, Wisconsin  54303
Bay Area Cancer Care Center at Bay Area Medical CenterMarinette, Wisconsin  54143
North Colorado Medical CenterGreeley, Colorado  80631
McKee Medical CenterLoveland, Colorado  80539
Wayne Memorial Hospital, IncorporatedGoldsboro, North Carolina  27534
Memorial Cancer Institute at Memorial Regional HospitalHollywood, Florida  33021
New York Weill Cornell Cancer Center at Cornell UniversityNew York, New York  10021
Don Monti Comprehensive Cancer Center at North Shore University HospitalManhasset, New York  11030
Oklahoma University Cancer InstituteOklahoma City, Oklahoma  73104
Geisinger Cancer Institute at Geisinger HealthDanville, Pennsylvania  17822-0001
Gundersen Lutheran Center for Cancer and BloodLa Crosse, Wisconsin  54601
Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical CenterHartford, Connecticut  06105
Front Range Cancer SpecialistsFort Collins, Colorado  80528
Poudre Valley HospitalFort Collins, Colorado  80524
Ella Milbank Foshay Cancer Center at Jupiter Medical CenterJupiter, Florida  33458
Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical CenterBoise, Idaho  83706
St. Joseph Medical CenterBloomington, Illinois  61701
Eureka Community HospitalEureka, Illinois  61530
BroMenn Regional Medical CenterNormal, Illinois  61761
Community Cancer CenterNormal, Illinois  61761
Community Hospital of OttawaOttawa, Illinois  61350
Oncology Hematology Associates of Central Illinois, PC - OttawaOttawa, Illinois  61350
Cancer Treatment Center at Pekin HospitalPekin, Illinois  61554
Oncology Hematology Associates of Central Illinois, PC - PeoriaPeoria, Illinois  61615
OSF St. Francis Medical CenterPeoria, Illinois  61637
Proctor HospitalPeoria, Illinois  61614
Illinois Valley Community HospitalPeru, Illinois  61354
Cancer Center of Kansas, PA - Dodge CityDodge City, Kansas  67801
Hickman Cancer Center at Bixby Medical CenterAdrian, Michigan  49221
Community Cancer Center of MonroeMonroe, Michigan  48162
Immanuel Medical CenterOmaha, Nebraska  68122
Creighton University Medical CenterOmaha, Nebraska  68131-2197
Wood County Oncology CenterBowling Green, Ohio  43402
Lima Memorial HospitalLima, Ohio  45804
Northwest Ohio Oncology CenterMaumee, Ohio  43537
Toledo Clinic - OregonOregon, Ohio  43616
St. Charles Mercy HospitalOregon, Ohio  43616
Mercy Hospital of TiffinTiffin, Ohio  44883
Toledo Clinic, Incorporated - Main ClinicToledo, Ohio  43623
Fulton County Health CenterWauseon, Ohio  43567
Oncology Services of AberdeenAberdeen, South Dakota  57401
Danville Regional Medical CenterDanville, Virginia  24541
Holy Family Memorial Medical Center Cancer Care CenterManitowoc, Wisconsin  54221-1450
St. Anthony Central HospitalDenver, Colorado  80204-1335
Exempla Lutheran Medical CenterWheat Ridge, Colorado  80033
Cancer Resource Center - LincolnLincoln, Nebraska  68510
Randolph HospitalAsheboro, North Carolina  27203
Moses Cone Regional Cancer Center at Wesley Long Community HospitalGreensboro, North Carolina  27401
Annie Penn Cancer CenterReidsville, North Carolina  27320
Altru Cancer Center at Altru HospitalGrand Forks, North Dakota  58201
Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross HospitalFort Lauderdale, Florida  33308
John B. Amos Cancer CenterColumbus, Georgia  31904
McFarland Clinic, PCAmes, Iowa  50010
Cancer Center of Kansas, PA - ChanuteChanute, Kansas  66720
Cancer Center of Kansas, PA - El DoradoEl Dorado, Kansas  67042
Cancer Center of Kansas - Fort ScottFort Scott, Kansas  66701
Cancer Center of Kansas-IndependenceIndependence, Kansas  67301
Cancer Center of Kansas, PA - KingmanKingman, Kansas  67068
Lawrence Memorial HospitalLawrence, Kansas  66044
Cancer Center of Kansas, PA - LiberalLiberal, Kansas  67905
Cancer Center of Kansas, PA - NewtonNewton, Kansas  67114
Cancer Center of Kansas, PA - ParsonsParsons, Kansas  67357
Cancer Center of Kansas, PA - PrattPratt, Kansas  67124
Cancer Center of Kansas, PA - SalinaSalina, Kansas  67401
Cancer Center of Kansas, PA - WellingtonWellington, Kansas  67152
Cancer Center of Kansas, PA - WichitaWichita, Kansas  67214
Associates in Womens Health, PA - North ReviewWichita, Kansas  67208
Cancer Center of Kansas, PA - Medical Arts TowerWichita, Kansas  67208
Cancer Center of Kansas, PA - WinfieldWinfield, Kansas  67156
Foote Memorial HospitalJackson, Michigan  49201
St. Mary Mercy HospitalLivonia, Michigan  48154
Mercy Memorial Hospital - MonroeMonroe, Michigan  48162
St. Joseph Mercy OaklandPontiac, Michigan  48341-2985
Mercy Regional Cancer Center at Mercy HospitalPort Huron, Michigan  48060
Seton Cancer Institute at Saint Mary's - SaginawSaginaw, Michigan  48601
Alegant Health Cancer Center at Bergan Mercy Medical CenterOmaha, Nebraska  68124
Monter Cancer Center of the North Shore-LIJ Health SystemLake Success, New York  11042
Hematology Oncology CenterElyria, Ohio  44035
Community Cancer CenterElyria, Ohio  44035
Flower Hospital Cancer CenterSylvania, Ohio  43560
St. Anne Mercy HospitalToledo, Ohio  43623
Geisinger Hazleton Cancer CenterHazleton, Pennsylvania  18201
Fredericksburg Oncology, IncorporatedFredericksburg, Virginia  22401
Mid Dakota Clinic, PCBismarck, North Dakota  58501
Queen's Cancer Institute at Queen's Medical CenterHonolulu, Hawaii  96813
Pardee Memorial HospitalHendersonville, North Carolina  28791
Kinston Medical SpecialistsKinston, North Carolina  28501
Resurrection Medical CenterChicago, Illinois  60631
Doctors Medical Center - San Pablo CampusSan Pablo, California  94806
Galesburg Clinic, PCGalesburg, Illinois  61401
Contra Costa Regional Medical CenterMartinez, California  94553-3156
El Camino Hospital Cancer CenterMountain View, California  94040
Larry G Strieff MD Medical CorporationOakland, California  94609
Tom K Lee, IncorporatedOakland, California  94609
Bay Area Breast Surgeons, IncorporatedOakland, California  94609
Kapiolani Medical Center at Pali MomiAiea, Hawaii  96701
Kapiolani Medical Center for Women and ChildrenHonolulu, Hawaii  96826
Straub Clinic and Hospital, IncorporatedHonolulu, Hawaii  96813
OnCare Hawaii, Incorporated - KuakiniHonolulu, Hawaii  96817
OnCare Hawaii, Incorporated - LusitanaHonolulu, Hawaii  96813
Illinois CancerCare - BloomingtonBloomington%, Illinois  61701
Illinois CancerCare - CantonCanton, Illinois  61520
Illinois CancerCare - CarthageCarthage, Illinois  62321
Illinois CancerCare - EurekaEureka, Illinois  61530
Illinois CancerCare - HavanaHavana, Illinois  62644
Illinois CancerCare - Kewanee ClinicKewanee, Illinois  61443
Illinois CancerCare - MacombMacomb, Illinois  61455
OSF Holy Family Medical CenterMonmouth, Illinois  61462
Illinois CancerCare - MonmouthMonmouth, Illinois  61462
Illinois CancerCare - Community Cancer CenterNormal, Illinois  61761
Illinois CancerCare - PekinPekin, Illinois  61603
Illinois CancerCare - PeruPeru, Illinois  61354
Illinois CancerCare - PrincetonPrinceton, Illinois  61356
Illinois CancerCare - Spring ValleySpring Valley, Illinois  61362
Fountain Valley, California  92708
Medcenter One Hospital Cancer Care CenterBismarck, North Dakota  58501
St. Alexius Medical Center Cancer CenterBismarck, North Dakota  58502
Florida Hospital Memorial Medical CenterDaytona Beach, Florida  32117
Castle Medical CenterKailua, Hawaii  96734
Kauai Medical ClinicLihue, Hawaii  96766
Lakeside HospitalOmaha, Nebraska  68130
St. Nicholas HospitalSheboygan, Wisconsin  53081
Kuakini Medical CenterHonolulu, Hawaii  96817
Oncare Hawaii, Incorporated - Pali MomiAiea, Hawaii  96701