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

NCT01572727 | Completed Phase 2 Results DMC

• 2 other identifiers: CBKM120F22022011-005932-24
• Study Type: interventional
• Target: 416
• Locations: 21 countries
• Sites: 108

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.

Conditions

Breast Cancer

Keywords

BKM120; paclitaxel; breast cancer; metastatic; locally advanced; PI3K; PIK3CA; PTEN

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS)Assessed by Local Investigator's Assessment (Phase ll)

  PFS was defined as the time from the date of randomization to the date of the event, defined as the first radiologically documented disease progression or death due to any cause. Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

  Every 8 weeks from randomization until disease progression up to 10 months after futility was analyzed

Secondary Outcomes (7)

• Overall Survival by Kaplan-Meier Estimate (Phase ll)

  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

• Overall Response Rate (Phase ll)

  every 8 weeks after randomization Up to 3 months after end of Treatment

• Duration of Response (Phase Lll)

  every 8 weeks after randomization Up to 3 months after end of Treatment

• Time to Response (Phase Lll)

  every 8 weeks after randomization Up to 3 months after end of Treatment

• Clinical Benefit Rate (CBR) (Phase ll)

  every 8 weeks after randomization Up to 3 months after end of Treatment

Study Arms (2)

BKM120 and paclitaxel

EXPERIMENTAL

Adult females with histologically confirmed, inoperable, locally advanced or metastatic HER2- BC who received study drug plus paclitaxel.

Drug: Paclitaxel; Drug: BKM120

Placebo and paclitaxel

ACTIVE COMPARATOR

Adult females with histologically confirmed, inoperable, locally advanced or metastatic HER2- BC who received placebo plus paclitaxel.

Drug: Paclitaxel; Drug: BKM120 matching placebo

Interventions

Paclitaxel DRUG

intravenous paclitaxel 80 mg/m2 per week given until progression

Also known as: Taxol

BKM120 and paclitaxel; Placebo and paclitaxel

BKM120 matching placebo DRUG

Buparlisib maching plaxcebo were supplied as 100 mg and 50 mg hard gelatin capsules. Buparlisib placebo was dosed on a flat scale of mg/day and was not adjusted to body weight or body surface area.

Placebo and paclitaxel

BKM120 DRUG

Buparlisib (BKM120) were supplied as 100 mg and 50 mg hard gelatin capsules. Buparlisib was dosed on a flat scale of mg/day and was not adjusted to body weight or body surface area.

Also known as: Buparlisib

BKM120 and paclitaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (112)

Ironwood Cancer and Research Centers SC

Chandler, Arizona, 85224, United States

Location

Arizona Oncology Associates Dept of Oncology

Phoenix, Arizona, United States

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Highlands Oncology Group Dept of Highlands Oncology Grp

Fayetteville, Arkansas, 72703, United States

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California Cancer Care Marian Speciality

Greenbrae, California, 94904, United States

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Rocky Mountain Cancer Centers RMCC Hale Pkwy

Greenwood Village, Colorado, United States

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H. Lee Moffitt Cancer Center & Research Institute SC

Tampa, Florida, 33612, United States

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Emory University School of Medicine/Winship Cancer Institute Dept.of WinshipCancerInst. (2)

Atlanta, Georgia, 30322, United States

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Northwest Georgia Oncology Center NW Georgia Onc

Marietta, Georgia, 30060, United States

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University of Kansas Cancer Center Univ Kansas 2

Kansas City, Kansas, 66160, United States

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Norton Healthcare, Inc.

Louisville, Kentucky, 40202, United States

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Washington University School of Medicine Regulatory

St Louis, Missouri, 63110, United States

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University of Nebraska Medical Center Unv Nebraska Med Ctr (2)

Omaha, Nebraska, 68198, United States

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University of New Mexico Cancer Research Center Dept of Univ New Mexico

Albuquerque, New Mexico, 87131, United States

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New York Oncology Hematology, P.C. Dept. of New York Oncology. PC

Troy, New York, 12180, United States

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Ohio State Comprehensive Cancer Center/James Cancer Hospital SC-1

Columbus, Ohio, 43210, United States

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University of Oklahoma Health Sciences Center OUHSC 2

Oklahoma City, Oklahoma, 73104, United States

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Northwest Cancer Specialists Vancouver Loc

Portland, Oregon, 97210, United States

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Baylor Health Care System/Sammons Cancer Center Baylor Texas Oncology

Dallas, Texas, 75246, United States

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University of Texas Southwestern Medical Center Harry Hines

Dallas, Texas, 75390, United States

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Cancer Care Centers of South Texas / HOAST CCC of So. TX- San Antonio

San Antonio, Texas, 78229, United States

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Medical Oncology & Hematology Associates of Northern VA Med Onc Hem Northern VA

Reston, Virginia, 20190, United States

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Novartis Investigative Site

Sydney, New South Wales, 2060, Australia

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Novartis Investigative Site

Geelong, Victoria, 3220, Australia

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Novartis Investigative Site

Parkville, Victoria, 3050, Australia

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Novartis Investigative Site

Nedlands, Western Australia, 6009, Australia

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Novartis Investigative Site

Salzburg, 5020, Austria

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Vienna, A-1090, Austria

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Novartis Investigative Site

Charleroi, 6000, Belgium

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Novartis Investigative Site

Liège, 4000, Belgium

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Novartis Investigative Site

Ottignies, 1340, Belgium

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Novartis Investigative Site

Sint-Niklaas, 9100, Belgium

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Wilrijk, 2610, Belgium

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Fortaleza, Ceará, 60336-045, Brazil

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São Paulo, São Paulo, 01221-020, Brazil

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Novartis Investigative Site

São Paulo, São Paulo, 01246-000, Brazil

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São Paulo, São Paulo, 01317-002, Brazil

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Montreal, Quebec, H4A 3J1, Canada

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Brno, Czech Republic, 656 53, Czechia

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Novartis Investigative Site

Olomouc, 775 20, Czechia

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Prague, 128 08, Czechia

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Angers, 49055, France

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Bordeaux, 33076, France

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Créteil, 94010, France

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La Roche-sur-Yon, 85925, France

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Le Mans, 72015, France

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Marseille, 13273, France

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Nice, 06189, France

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Saint-Herblain, 44805, France

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Toulouse, 31059, France

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Villejuif, 94805, France

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Bonn, 53111, Germany

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Dresden, 01307, Germany

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Erlangen, 91054, Germany

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Frankfurt, 60389, Germany

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Fulda, 36043, Germany

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Mainz, 55131, Germany

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München, 80637, Germany

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Ravensburg, 88214, Germany

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Ulm, 89081, Germany

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Hong Kong SAR, Hong Kong

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Budapest, 1134, Hungary

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Debrecen, 4032, Hungary

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Szolnok, H-5000, Hungary

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Ramat Gan, 5266202, Israel

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Tel Aviv, 6423906, Israel

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Cona, FE, 44100, Italy

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Genova, GE, 16132, Italy

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Monza, MB, 20900, Italy

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Messina, ME, 98158, Italy

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Milan, MI, 20141, Italy

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Nagoya, Aichi-ken, 464-8681, Japan

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Nagoya, Aichi-ken, 467-8602, Japan

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Sapporo, Hokkaido, 135-8550, Japan

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Isehara, Kanagawa, 259-1193, Japan

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Kawasaki, Kanagawa, 216-8511, Japan

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Yokohama, Kanagawa, 241-8515, Japan

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Kumamoto, Kumamoto, 860-8556, Japan

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Osaka, Osaka, 537-8511, Japan

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Osaka, Osaka, 540-0006, Japan

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Novartis Investigative Site

Suita, Osaka, 565-0871, Japan

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Koto, Tokyo, 135-8550, Japan

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Novartis Investigative Site

Breda, Netherlands, 4819 EV, Netherlands

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Rotterdam, 3075 EA, Netherlands

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Novartis Investigative Site

Saint Petersburg, Russia, 197022, Russia

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Novartis Investigative Site

Saint Petersburg, 197758, Russia

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Singapore, Singapore, 119228, Singapore

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Johannesburg, 2196, South Africa

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Seoul, Korea, 03080, South Korea

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Novartis Investigative Site

Seoul, Korea, 05505, South Korea

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Novartis Investigative Site

Seoul, Korea, 06351, South Korea

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Córdoba, Andalusia, 14004, Spain

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Málaga, Andalusia, 29010, Spain

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Seville, Andalusia, 41013, Spain

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Novartis Investigative Site

Barcelona, Catalonia, 08003, Spain

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Novartis Investigative Site

Barcelona, Catalonia, 08036, Spain

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Novartis Investigative Site

L'Hospitalet de Llobregat, Catalonia, 08907, Spain

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Novartis Investigative Site

A Coruña, Galicia, 15009, Spain

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Novartis Investigative Site

Madrid, Madrid, 28007, Spain

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Novartis Investigative Site

Madrid, Madrid, 28033, Spain

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Novartis Investigative Site

Madrid, Madrid, 28034, Spain

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Novartis Investigative Site

Madrid, Madrid, 28040, Spain

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Novartis Investigative Site

San Cristóbal de La Laguna, Santa Cruz de Tenerife, 38320, Spain

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Valencia, Valencia, 46009, Spain

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Valencia, Valencia, 46010, Spain

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Novartis Investigative Site

Zaragoza, Zaragoza, 50009, Spain

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Novartis Investigative Site

Taipei, Taiwan, 10048, Taiwan

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Novartis Investigative Site

Kuei-Shan Chiang, Taoyuan/ Taiwan ROC, 33305, Taiwan

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Novartis Investigative Site

New Taipei City, 23561, Taiwan

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Novartis Investigative Site

Maidstone, Kent, M16 9QQ, United Kingdom

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Novartis Investigative Site

Glasgow - Scotland, G12 OYN, United Kingdom

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Novartis Investigative Site

London, United Kingdom

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Novartis Investigative Site

Metropolitan Borough of Wirral, CH63 3JY, United Kingdom

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MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis; Hereditary Sensory and Autonomic Neuropathies

Interventions

Paclitaxel; NVP-BKM120

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Limitations and Caveats

Safety set: all randomized pts who received at least 1 dose of the study treatment (either buparlisib + paclitaxel or matching placebo + paclitaxel) \& had at least 1 post-baseline safety assessment;13 of 416 pts didn't meet this criteria; safety =403

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

trialandresults.registries@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 4, 2012
• First Posted: April 6, 2012
• Study Start: August 1, 2012
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: March 9, 2017
• Results First Posted: January 27, 2017

Record last verified: 2017-01

Locations

BE (5); ES (15); US (21); NL (2); AU (2); FR (10); BR (4); CA (1); DE (9); RU (2); HK (1); SG (1); CZ (3); ZA (1); JP (11); GB (4); IL (2); HU (3); TW (3); IT (5); KR (3)