Clinical trial NCT01572727: A Study of the Experimental Drug BKM120 With Paclitaxel in Patients With HER2 Negative, Locally Advanced or Metastatic Breast Cancer, With or Without PI3K Activation
Official title: A Randomized, Double-blind, Placebo Controlled, Phase II/III Study of BKM120 Plus Paclitaxel in Patients With HER2 Negative Inoperable Locally Advanced or Metastatic Breast Cancer, With or Without PI3K Pathway Activation.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Breast Cancer
Keywords: BKM120
paclitaxel
breast cancer
metastatic
locally advanced
PI3K
PIK3CA
PTEN
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2012-04-06
Enrollment: 416
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study evaluated whether the addition of daily BKM120 to weekly paclitaxel was effective and safe in treating patients with HER2- locally advanced or metastatic breast cancer.

Detailed description: Based on the efficacy results at the time of the interim analyses, the DMC recommended stopping the study at Phase II during the interim as it met the protocol pre-specified futility criteria. Consequently, the Phase III portion of the study was not conducted.

Eligibility criteria: Inclusion Criteria:

* Breast cancer that is locally advanced or metastatic
* HER2 negative disease, and a known hormone receptor status - ER/PgR (common breast cancer classification tests)
* A tumor sample must be shipped to a central lab for identification of biomarkers (PI3K activation status) before randomization
* Adequate bone marrow and organ function
* Measurable or non-measurable disease

Exclusion Criteria:

* Prior chemotherapy for locally advanced or metastatic disease
* Previous treatment with PI3K or AKT inhibitors
* Patient has symptomatic CNS metastases
* Concurrent malignancy or malignancy within 3 years of study enrollment
* Hematopoietic colony-stimulating growth factors or radiation within 2-4 weeks prior to starting study drug
* Increasing or chronic treatment (\> 5 days) with corticosteroids or another immunosuppressive agent
* Active heart (cardiac) disease as defined in the protocol
* Known hypersensitivity or contraindications to use paclitaxel
* Pregnant or nursing (lactating) woman
* Certain scores on an anxiety and depression mood questionaire given at screening
* Other protocol defined criteria may apply

Primary outcomes:
measure: Progression-free Survival (PFS)Assessed by Local Investigator's Assessment (Phase ll)
timeFrame: Every 8 weeks from randomization until disease progression up to 10 months after futility was analyzed
Secondary outcomes:
measure: Overall Survival by Kaplan-Meier Estimate (Phase ll)
timeFrame: every 3 months until death, lost to follow-up, or withdrawal of consent to survival follow-up, up to 10 months after futility was analyzed
measure: Overall Response Rate (Phase ll)
timeFrame: every 8 weeks after randomization Up to 3 months after end of Treatment
measure: Duration of Response (Phase Lll)
timeFrame: every 8 weeks after randomization Up to 3 months after end of Treatment
measure: Time to Response (Phase Lll)
timeFrame: every 8 weeks after randomization Up to 3 months after end of Treatment
measure: Clinical Benefit Rate (CBR) (Phase ll)
timeFrame: every 8 weeks after randomization Up to 3 months after end of Treatment
measure: Plasma Concentration-time Profiles of BKM120 - Pharmacokinetics (PK) (Phase Lll)
timeFrame: Cycle 1 day 1, 15, 16, 22 and Cycle 2 day 1.
measure: Time to Definitive Deterioration of ECOG Performance Status (Phase Lll)
timeFrame: every 4 weeks
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Ironwood Cancer and Research Centers SC
state: Arizona
city: Phoenix
country: United States
facility: Arizona Oncology Associates Dept of Oncology
state: Arizona
city: Fayetteville
country: United States
facility: Highlands Oncology Group Dept of Highlands Oncology Grp
state: Arkansas
city: Greenbrae
country: United States
facility: California Cancer Care Marian Speciality
state: California
city: Greenwood Village
country: United States
facility: Rocky Mountain Cancer Centers RMCC Hale Pkwy
state: Colorado
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute SC
state: Florida
city: Atlanta
country: United States
facility: Emory University School of Medicine/Winship Cancer Institute Dept.of WinshipCancerInst. (2)
state: Georgia
city: Marietta
country: United States
facility: Northwest Georgia Oncology Center NW Georgia Onc
state: Georgia
city: Kansas City
country: United States
facility: University of Kansas Cancer Center Univ Kansas 2
state: Kansas
city: Louisville
country: United States
facility: Norton Healthcare, Inc.
state: Kentucky
city: St. Louis
country: United States
facility: Washington University School of Medicine Regulatory
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center Unv Nebraska Med Ctr (2)
state: Nebraska
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Research Center Dept of Univ New Mexico
state: New Mexico
city: Troy
country: United States
facility: New York Oncology Hematology, P.C. Dept. of New York Oncology. PC
state: New York
city: Columbus
country: United States
facility: Ohio State Comprehensive Cancer Center/James Cancer Hospital SC-1
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center OUHSC 2
state: Oklahoma
city: Portland
country: United States
facility: Northwest Cancer Specialists Vancouver Loc
state: Oregon
city: Dallas
country: United States
facility: Baylor Health Care System/Sammons Cancer Center Baylor Texas Oncology
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center Harry Hines
state: Texas
city: San Antonio
country: United States
facility: Cancer Care Centers of South Texas / HOAST CCC of So. TX- San Antonio
state: Texas
city: Reston
country: United States
facility: Medical Oncology & Hematology Associates of Northern VA Med Onc Hem Northern VA
state: Virginia
city: Sydney
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Geelong
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Parkville
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Nedlands
country: Australia
facility: Novartis Investigative Site
state: Western Australia
city: Salzburg
country: Austria
facility: Novartis Investigative Site
city: Vienna
country: Austria
facility: Novartis Investigative Site
city: Charleroi
country: Belgium
facility: Novartis Investigative Site
city: Liege
country: Belgium
facility: Novartis Investigative Site
city: Liège
country: Belgium
facility: Novartis Investigative Site
city: Ottignies
country: Belgium
facility: Novartis Investigative Site
city: Sint-Niklaas
country: Belgium
facility: Novartis Investigative Site
city: Wilrijk
country: Belgium
facility: Novartis Investigative Site
city: Fortaleza
country: Brazil
facility: Novartis Investigative Site
state: CE
city: São Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: São Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: São Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Brno
country: Czech Republic
facility: Novartis Investigative Site
city: Olomouc
country: Czech Republic
facility: Novartis Investigative Site
city: Praha 2
country: Czech Republic
facility: Novartis Investigative Site
city: Angers Cedex 02
country: France
facility: Novartis Investigative Site
city: Bordeaux
country: France
facility: Novartis Investigative Site
city: Creteil
country: France
facility: Novartis Investigative Site
city: La Roche sur Yon cedex 9
country: France
facility: Novartis Investigative Site
city: Le Mans Cedex
country: France
facility: Novartis Investigative Site
city: Marseille
country: France
facility: Novartis Investigative Site
city: Nice Cedex 2
country: France
facility: Novartis Investigative Site
city: Saint Herblain cedex
country: France
facility: Novartis Investigative Site
city: Toulouse Cedex 9
country: France
facility: Novartis Investigative Site
city: Villejuif Cedex
country: France
facility: Novartis Investigative Site
city: Bonn
country: Germany
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Erlangen
country: Germany
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Fulda
country: Germany
facility: Novartis Investigative Site
city: Mainz
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Ravensburg
country: Germany
facility: Novartis Investigative Site
city: Ulm
country: Germany
facility: Novartis Investigative Site
city: Hong Kong SAR
country: Hong Kong
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Debrecen
country: Hungary
facility: Novartis Investigative Site
city: Szolnok
country: Hungary
facility: Novartis Investigative Site
city: Ramat Gan
country: Israel
facility: Novartis Investigative Site
city: Tel Aviv
country: Israel
facility: Novartis Investigative Site
city: Cona
country: Italy
facility: Novartis Investigative Site
state: FE
city: Genova
country: Italy
facility: Novartis Investigative Site
state: GE
city: Monza
country: Italy
facility: Novartis Investigative Site
state: MB
city: Messina
country: Italy
facility: Novartis Investigative Site
state: ME
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Nagoya-city
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Nagoya
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Sapporo
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Isehara-city
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Kawasaki-city
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Yokohama
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Kumamoto City
country: Japan
facility: Novartis Investigative Site
state: Kumamoto
city: Suita-city
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Koto
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Osaka
country: Japan
facility: Novartis Investigative Site
city: Osaka
country: Japan
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Breda
country: Netherlands
facility: Novartis Investigative Site
city: Rotterdam
country: Netherlands
facility: Novartis Investigative Site
city: St.- Petersburg
country: Russian Federation
facility: Novartis Investigative Site
state: Russia
city: St. Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Johannesburg
country: South Africa
facility: Novartis Investigative Site
city: Cordoba
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Malaga
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Sevilla
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Hospitalet de LLobregat
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: A Coruna
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: La Laguna
country: Spain
facility: Novartis Investigative Site
state: Santa Cruz de Tenerife
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Zaragoza
country: Spain
facility: Novartis Investigative Site
city: Kuei-Shan Chiang
country: Taiwan
facility: Novartis Investigative Site
state: Taoyuan/ Taiwan ROC
city: New Taipei City
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Maidstone
country: United Kingdom
facility: Novartis Investigative Site
state: Kent
city: Glasgow - Scotland
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Wirral
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: