Panobinostat and Letrozole in Treating Patients With Metastatic Breast Cancer

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01105312
• Other study ID #: NCCTG-N093B
• Secondary ID: NCCTG-N093BCDR00
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• First received: April 15, 2010
• Last updated: August 12, 2016
• Start date: September 2010

Study information

• Verified date: August 2016
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 48
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• letrozole

• panobinostat

Genetic:
• RNA analysis

• microarray analysis

• reverse transcriptase-polymerase chain reaction

Other:
• enzyme-linked immunosorbent assay

• immunohistochemistry staining method

• laboratory biomarker analysis

Locations

Country	Name	City	State
United States	Oncology Services of Aberdeen	Aberdeen	South Dakota
United States	Hickman Cancer Center at Bixby Medical Center	Adrian	Michigan
United States	Kapiolani Medical Center at Pali Momi	Aiea	Hawaii
United States	Oncare Hawaii, Incorporated - Pali Momi	Aiea	Hawaii
United States	McFarland Clinic, PC	Ames	Iowa
United States	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan
United States	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan
United States	Randolph Hospital	Asheboro	North Carolina
United States	Aurora Presbyterian Hospital	Aurora	Colorado
United States	Alvin and Lois Lapidus Cancer Institute at Sinai Hospital	Baltimore	Maryland
United States	Medcenter One Hospital Cancer Care Center	Bismarck	North Dakota
United States	Mid Dakota Clinic, PC	Bismarck	North Dakota
United States	St. Alexius Medical Center Cancer Center	Bismarck	North Dakota
United States	Illinois CancerCare - Bloomington	Bloomington	Illinois
United States	St. Joseph Medical Center	Bloomington	Illinois
United States	Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center	Boise	Idaho
United States	Boulder Community Hospital	Boulder	Colorado
United States	Wood County Oncology Center	Bowling Green	Ohio
United States	Illinois CancerCare - Canton	Canton	Illinois
United States	Illinois CancerCare - Carthage	Carthage	Illinois
United States	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas
United States	Presbyterian Cancer Center at Presbyterian Hospital	Charlotte	North Carolina
United States	Louis A. Weiss Memorial Hospital	Chicago	Illinois
United States	Resurrection Medical Center	Chicago	Illinois
United States	Penrose Cancer Center at Penrose Hospital	Colorado Springs	Colorado
United States	Ellis Fischel Cancer Center at University of Missouri - Columbia	Columbia	Missouri
United States	John B. Amos Cancer Center	Columbus	Georgia
United States	Danville Regional Medical Center	Danville	Virginia
United States	Geisinger Cancer Institute at Geisinger Health	Danville	Pennsylvania
United States	Florida Hospital Memorial Medical Center	Daytona Beach	Florida
United States	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan
United States	Porter Adventist Hospital	Denver	Colorado
United States	Presbyterian - St. Luke's Medical Center	Denver	Colorado
United States	Rose Medical Center	Denver	Colorado
United States	St. Anthony Central Hospital	Denver	Colorado
United States	St. Joseph Hospital	Denver	Colorado
United States	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas
United States	CCOP - Hematology-Oncology Associates of Central New York	East Syracuse	New York
United States	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas
United States	Community Cancer Center	Elyria	Ohio
United States	Hematology Oncology Center	Elyria	Ohio
United States	Swedish Medical Center	Englewood	Colorado
United States	Eureka Community Hospital	Eureka	Illinois
United States	Illinois CancerCare - Eureka	Eureka	Illinois
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Front Range Cancer Specialists	Fort Collins	Colorado
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital	Fort Lauderdale	Florida
United States	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas
United States	Fredericksburg Oncology, Incorporated	Fredericksburg	Virginia
United States	Galesburg Clinic, PC	Galesburg	Illinois
United States	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina
United States	Altru Cancer Center at Altru Hospital	Grand Forks	North Dakota
United States	North Colorado Medical Center	Greeley	Colorado
United States	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin
United States	Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin
United States	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	Moses Cone Regional Cancer Center at Wesley Long Community Hospital	Greensboro	North Carolina
United States	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan
United States	Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center	Hartford	Connecticut
United States	Illinois CancerCare - Havana	Havana	Illinois
United States	Geisinger Hazleton Cancer Center	Hazleton	Pennsylvania
United States	Pardee Memorial Hospital	Hendersonville	North Carolina
United States	Memorial Cancer Institute at Memorial Regional Hospital	Hollywood	Florida
United States	Cancer Research Center of Hawaii	Honolulu	Hawaii
United States	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii
United States	Kuakini Medical Center	Honolulu	Hawaii
United States	OnCare Hawaii, Incorporated - Kuakini	Honolulu	Hawaii
United States	OnCare Hawaii, Incorporated - Lusitana	Honolulu	Hawaii
United States	Queen's Cancer Institute at Queen's Medical Center	Honolulu	Hawaii
United States	Straub Clinic and Hospital, Incorporated	Honolulu	Hawaii
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	Foote Memorial Hospital	Jackson	Michigan
United States	Mayo Clinic - Jacksonville	Jacksonville	Florida
United States	Ella Milbank Foshay Cancer Center at Jupiter Medical Center	Jupiter	Florida
United States	Castle Medical Center	Kailua	Hawaii
United States	Illinois CancerCare - Kewanee Clinic	Kewanee	Illinois
United States	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas
United States	Kinston Medical Specialists	Kinston	North Carolina
United States	Gundersen Lutheran Center for Cancer and Blood	La Crosse	Wisconsin
United States	Monter Cancer Center of the North Shore-LIJ Health System	Lake Success	New York
United States	Sparrow Regional Cancer Center	Lansing	Michigan
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Cancer Center of Kansas, PA - Liberal	Liberal	Kansas
United States	Kauai Medical Clinic	Lihue	Hawaii
United States	Lima Memorial Hospital	Lima	Ohio
United States	Cancer Resource Center - Lincoln	Lincoln	Nebraska
United States	St. Mary Mercy Hospital	Livonia	Michigan
United States	Sky Ridge Medical Center	Lone Tree	Colorado
United States	Hope Cancer Care Center at Longmont United Hospital	Longmont	Colorado
United States	McKee Medical Center	Loveland	Colorado
United States	Illinois CancerCare - Macomb	Macomb	Illinois
United States	Don Monti Comprehensive Cancer Center at North Shore University Hospital	Manhasset	New York
United States	Holy Family Memorial Medical Center Cancer Care Center	Manitowoc	Wisconsin
United States	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin
United States	Contra Costa Regional Medical Center	Martinez	California
United States	Northwest Ohio Oncology Center	Maumee	Ohio
United States	CCOP - Mount Sinai Medical Center	Miami Beach	Florida
United States	Illinois CancerCare - Monmouth	Monmouth	Illinois
United States	OSF Holy Family Medical Center	Monmouth	Illinois
United States	Community Cancer Center of Monroe	Monroe	Michigan
United States	Mercy Memorial Hospital - Monroe	Monroe	Michigan
United States	El Camino Hospital Cancer Center	Mountain View	California
United States	Long Island Jewish Medical Center	New Hyde Park	New York
United States	New York Weill Cornell Cancer Center at Cornell University	New York	New York
United States	Cancer Center of Kansas, PA - Newton	Newton	Kansas
United States	BroMenn Regional Medical Center	Normal	Illinois
United States	Community Cancer Center	Normal	Illinois
United States	Illinois CancerCare - Community Cancer Center	Normal	Illinois
United States	Bay Area Breast Surgeons, Incorporated	Oakland	California
United States	CCOP - Bay Area Tumor Institute	Oakland	California
United States	Larry G Strieff MD Medical Corporation	Oakland	California
United States	Tom K Lee, Incorporated	Oakland	California
United States	Oklahoma University Cancer Institute	Oklahoma City	Oklahoma
United States	Alegant Health Cancer Center at Bergan Mercy Medical Center	Omaha	Nebraska
United States	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Immanuel Medical Center	Omaha	Nebraska
United States	Lakeside Hospital	Omaha	Nebraska
United States	St. Charles Mercy Hospital	Oregon	Ohio
United States	Toledo Clinic - Oregon	Oregon	Ohio
United States	Community Hospital of Ottawa	Ottawa	Illinois
United States	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois
United States	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas
United States	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois
United States	Illinois CancerCare - Pekin	Pekin	Illinois
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois
United States	OSF St. Francis Medical Center	Peoria	Illinois
United States	Proctor Hospital	Peoria	Illinois
United States	Illinois CancerCare - Peru	Peru	Illinois
United States	Illinois Valley Community Hospital	Peru	Illinois
United States	St. Joseph Mercy Oakland	Pontiac	Michigan
United States	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan
United States	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas
United States	Illinois CancerCare - Princeton	Princeton	Illinois
United States	St. Mary - Corwin Regional Medical Center	Pueblo	Colorado
United States	Annie Penn Cancer Center	Reidsville	North Carolina
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan
United States	Cancer Center of Kansas, PA - Salina	Salina	Kansas
United States	Peninsula Regional Medical Center	Salisbury	Maryland
United States	Doctors Medical Center - San Pablo Campus	San Pablo	California
United States	Mayo Clinic Scottsdale	Scottsdale	Arizona
United States	St. Nicholas Hospital	Sheboygan	Wisconsin
United States	Illinois CancerCare - Spring Valley	Spring Valley	Illinois
United States	Geisinger Medical Group - Scenery Park	State College	Pennsylvania
United States	Flower Hospital Cancer Center	Sylvania	Ohio
United States	North Suburban Medical Center	Thornton	Colorado
United States	Mercy Hospital of Tiffin	Tiffin	Ohio
United States	Medical University of Ohio Cancer Center	Toledo	Ohio
United States	St. Anne Mercy Hospital	Toledo	Ohio
United States	St. Vincent Mercy Medical Center	Toledo	Ohio
United States	Toledo Clinic, Incorporated - Main Clinic	Toledo	Ohio
United States	Toledo Hospital	Toledo	Ohio
United States	Natalie Warren Bryant Cancer Center at St. Francis Hospital	Tulsa	Oklahoma
United States	St. John Macomb Hospital	Warren	Michigan
United States	Fulton County Health Center	Wauseon	Ohio
United States	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas
United States	Exempla Lutheran Medical Center	Wheat Ridge	Colorado
United States	Associates in Womens Health, PA - North Review	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas
United States	CCOP - Wichita	Wichita	Kansas
United States	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas
United States	Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center	Wilkes-Barre	Pennsylvania
United States	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas
United States	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum-tolerated dose (phase I)		Up to 2.5 months	Yes
Primary	Adverse events		Up to 2.5 months	Yes
Primary	Response rate (phase II)		Up to 5 years post-registration	No
Secondary	Survival time (phase II)		Up to 5 years post-registration	No
Secondary	Time-to-disease progression (phase II)		Up to 6 months	No
Secondary	Progression-free survival (phase II)		Up to 6 months	No
Secondary	Duration of response (phase II)		Up to 5 years post-registration	No
Secondary	Clinical benefit rate		Up to 6 months	No
Secondary	Time to treatment failure		Up to 5 years post-registration	No