A Phase III Study of BKM120 With Fulvestrant in Patients With HR+,HER2-, AI Treated, Locally Advanced or Metastatic Breast Cancer Who Progressed on or After mTORi

NCT01633060 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: CBKM120F23032012-002571-34
• Study Type: interventional
• Target: 432
• Locations: 22 countries
• Sites: 197

Brief Summary

This study was a multicenter, randomized, double-blind, placebo-controlled Phase III study to determine the efficacy and safety of treatment with Buparlisib plus Fulvestrant vs. Placebo plus Fulvestrant in postmenopausal women with hormone Receptor-positive (HR-positive), human epidermal growth factor receptor 2-negative (HER2-negative), aromatase inhibitor (AI)-treated, locally advanced or metastatic breast cancer whose disease progressed on or after mammalian target of rapamycin inhibitor (mTORi)-based treatment. Patients were randomized in 2:1 ratio to treatment with buparlisib 100 mg daily in combination with fulvestrant 500 mg or placebo daily in combination with fulvestrant 500 mg. Randomization was stratified according to visceral disease status (present or absent).

Conditions

Metastatic Breast Cancer

Keywords

BKM120; fulvestrant; breast cancer; metastatic; locally advanced; AI treated; mTOR inhibitor; PI3K; PIK3CA; PTEN; HER2-; HR+

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS) Based on Local Investigator Assessment - Full Analysis Set (FAS)

  Progression Free Survival (PFS) is defined as the time from date of randomization to the date of first radiologically documented progression or death due to any cause. If a patient did not progress or die at the time of the analysis data cut-off or start of new antineoplastic therapy, PFS was censored at the date of the last adequate tumor assessment before the earliest of the cut-off date or the start date of additional anti-neoplastic therapy. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria RECIST v1.1, as 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline and/or unequivocal progression of the non-target lesions and/or appearance of a new lesion. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 mm. Patients were followed up for approximately every 6 weeks after randomization.

  Every 6 weeks after randomization up to a maximum of 4 years

Secondary Outcomes (10)

• Overall Survival (OS) - Full Analysis Set (FAS)

  Every 6 weeks after randomization up to a maximum of 5 years

• Progression Free Survival (PFS) by PIK3CA Mutational Status

  Every 6 weeks after randomization up to a maximum of 5 years

• Overall Survival (OS) by PIK3CA Mutational Status

  Every 6 weeks after randomization up to a maximum of 5 years

• Overall Response Rate (ORR) by PIK3CA Mutational Status

  Every 6 weeks after randomization up to a maximum of 5 years

• Clinical Benefit Rate (CBR) by PIK3CA Mutational Status

  Week 14, Week 24

Study Arms (2)

BKM120 100mg + Fulvestrant

EXPERIMENTAL

BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol.

Drug: Fulvestrant; Drug: BKM120

Placebo + Fulvestrant

PLACEBO COMPARATOR

BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol.

Drug: Fulvestrant; Drug: BKM120 matching placebo

Interventions

Fulvestrant DRUG

Intramuscular fulvestrant 500 mg (Day 1 and Day 15 of Cycle 1 and Day 1 of every cycle thereafter)

BKM120 100mg + Fulvestrant; Placebo + Fulvestrant

BKM120 DRUG

BKM120 100 mg once daily

BKM120 100mg + Fulvestrant

BKM120 matching placebo DRUG

BKM120 matching placebo, once daily

Placebo + Fulvestrant

Eligibility Criteria

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

You may qualify if:

• Female patients age 18 years or older
• Histologically and/or cytologically confirmed diagnosis of breast cancer
• Radiologic evidence of inoperable locally advanced or metastatic breast cancer
• Adequate tumor tissue for the analysis of PI3K-related biomarkers
• Human epidermal growth factor receptor-2 (HER2) negative disease, and a known positive hormone receptor status
• Postmenopausal women
• Prior treatment with aromatase inhibitors
• Evidence of progression to the combination of mTORi and endocrine therapy given as the last therapy prior to study entry
• Adequate bone marrow and organ function
• ECOG performance status ≤ 2

You may not qualify if:

• Previous treatment with PI3K inhibitors, protein kinase B inhibitors or fulvestrant
• More than one chemotherapy line for metastatic disease
• Hypersensitivity to any of the excipients of buparlisib or fulvestrant
• Symptomatic central nervous system metastases
• Concurrent malignancy or malignancy within 3 years of study enrollment
• Certain drugs or radiation within 2-4 weeks of enrollment
• Increasing or chronic treatment (\>5 days) with corticosteroids or another immunosuppressive agent
• Certain scores on an anxiety and depression mood questionnaire given at screening
• Acute viral hepatitis or a history of chronic or active hepatitis B virus or hepatitis C virus
• Active cardiac disease or a history of cardiac dysfunction

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (197)

University of South Alabama / Mitchell Cancer Institute Univ South AL

Mobile, Alabama, 36688, United States

Location

Ironwood Cancer and Research Centers SC

Chandler, Arizona, 85224, United States

Location

Highlands Oncology Group

Fayetteville, Arkansas, 72703, United States

Location

Compassionate Cancer Care Medical Group CCCMG

Fountain Valley, California, 92708, United States

Location

Los Angeles Hematology/Oncology Medical Group Onc Dept.

Los Angeles, California, 90017, United States

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Cedars Sinai Medical Center SC-5

Los Angeles, California, 90048, United States

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University of California at Los Angeles UCLA SC

Los Angeles, California, 90095, United States

Location

Pacific Cancer Care

Monterey, California, 93940, United States

Location

Rocky Mountain Cancer Centers SC

Denver, Colorado, 80218, United States

Location

University Cancer & Blood Center, LLC

Athens, Georgia, 30607, United States

Location

Emory University School of Medicine/Winship Cancer Institute Emory

Atlanta, Georgia, 30322, United States

Location

Moanalua Medical Center. Attn: Oncology Dept

Honolulu, Hawaii, 96817, United States

Location

Edward Hospital Edward Hospital

Naperville, Illinois, 60540, United States

Location

Crescent City Research Consortium, LLC SC

Metairie, Louisiana, 70006, United States

Location

Lsu Health Sciences Center/ Lsu School of Medicine Lsu

New Orleans, Louisiana, 70115, United States

Location

John Ochsner Heart and Vascular Institute Clinical Trials Ochsner 2

New Orleans, Louisiana, 70121, United States

Location

LSU Health Sciences Center Feist-Weiller Cancer Center

New Orleans, Louisiana, 70122-2822, United States

Location

University of Maryland Medical Center Univ Maryland

Baltimore, Maryland, 21201, United States

Location

Mercy Medical Research Institute SC

Manchester, Missouri, 63021, United States

Location

Morristown Memorial Hospital Morristown Mem

Morristown, New Jersey, 07962, United States

Location

CINJ at Cooper University Hospital Dept of Onc

Voorhees Township, New Jersey, 08043, United States

Location

Clinical Research Alliance BKM120F2303

Lake Success, New York, 11042, United States

Location

Clinical Research Alliance

Lake Success, New York, 11042, United States

Location

Montefiore Medical Center Montefiore

The Bronx, New York, 10467, United States

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Northwest Cancer Specialists Compass Oncology -BKM

Portland, Oregon, 97210, United States

Location

Oregon Health and Science University SC-5

Portland, Oregon, 97239, United States

Location

University of Pittsburgh Cancer Institute Dept of Magee Women's Hospital

Pittsburgh, Pennsylvania, 15232, United States

Location

The West Clinic Dept. of the West Clinic

Memphis, Tennessee, 38120, United States

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Texas Oncology PA Dallas Presbyterian Hospital SC

Dallas, Texas, 75231, United States

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Texas Oncology Texas Oncology - Sammons

Dallas, Texas, 75246, United States

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Texas Oncology P A SC-Austin

Dallas, Texas, 75251, United States

Location

Texas Oncology P A Texas Oncology - Fort Worth (3

Dallas, Texas, 75251, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Texas Tech University Health Science Center Dept of Texas Tech

El Paso, Texas, 79905, United States

Location

The Methodist Hospital Cancer Center

Houston, Texas, 77030, United States

Location

US Oncology, P.A.

Tyler, Texas, 75702, United States

Location

Northwest Medical Specialties

Tacoma, Washington, 98405, United States

Location

Novartis Investigative Site

CABA, Buenos Aires, C1050AAK, Argentina

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Rosario, Santa Fe Province, S2000KZE, Argentina

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San Miguel de Tucumán, Tucumán Province, T4000IAK, Argentina

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Rio Negro, Viedma, 8500, Argentina

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Innsbruck, Tyrol, 6020, Austria

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Linz, 4010, Austria

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Salzburg, 5020, Austria

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Vienna, A-1090, Austria

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Brussels, 1000, Belgium

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Leuven, 3000, Belgium

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Liège, 4000, Belgium

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Namur, 5000, Belgium

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Plovdiv, 4000, Bulgaria

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Plovdiv, 4004, Bulgaria

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Sofia, 1303, Bulgaria

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Sofia, 1527, Bulgaria

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Sofia, 1756, Bulgaria

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Varna, 9010, Bulgaria

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Vratsa, 3000, Bulgaria

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Montreal, Quebec, H2W 1T8, Canada

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Montreal, Quebec, H3A 1A1, Canada

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Bogotá, Colombia

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Tampere, FIN-33521, Finland

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Nice, Alpes Maritimes, 06189, France

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Limoges, Haute Vienne, 87000, France

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Saint-Cloud, Hauts De Seine, 92210, France

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Saint-Herblain Cédex, 44805, France

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München, 81377, Germany

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Soest, 59494, Germany

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Tübingen, 72076, Germany

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Ulm, 89081, Germany

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Velbert, 42551, Germany

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Marousi, Athens, 15123, Greece

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Heraklion Crete, Greece, 711 10, Greece

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Athens, GR, 151 23, Greece

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Larissa, GR, 411 10, Greece

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Patra - RIO, GR, 265 04, Greece

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Thesaloniki, Thessaloniki, 54622, Greece

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Athens, 18547, Greece

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Athens, GR-115 22, Greece

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Budapest, 1134, Hungary

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Budapest, H-1122, Hungary

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Szeged, H-6720, Hungary

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Szolnok, H-5000, Hungary

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L’Aquila, AQ, 67100, Italy

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Bari, BA, 70124, Italy

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Benevento, BN, 82100, Italy

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Brindisi, BR, 72100, Italy

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Brescia, BS, 25123, Italy

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Monserrato, CA, 09042, Italy

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Cremona, CR, 26100, Italy

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Catania, CT, 95100, Italy

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Meldola, FC, 47014, Italy

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Cona, FE, 44100, Italy

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Florence, FI, 50134, Italy

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Lecco, LC, 23900, Italy

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Lecce, LE, 73100, Italy

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Monza, MB, 20900, Italy

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Macerata, MC, 62100, Italy

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Messina, ME, 98158, Italy

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Milan, MI, 20121, Italy

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Milan, MI, 20132, Italy

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Verona, VR, 37126, Italy

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Frattamaggiore, 80020, Italy

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Beirut, Lebanon

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El Achrafiyé, 166830, Lebanon

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Saida, 652, Lebanon

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Maastricht, AZ, 5800, Netherlands

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Breda, 4819 EV, Netherlands

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Delft, NL 2625 AD, Netherlands

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Deventer, 7416 SE, Netherlands

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Hoofddorp, 2134 TM, Netherlands

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Leiden, 2300 RC, Netherlands

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Sittard-Geleen, 6162 BG, Netherlands

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Zwolle, 8025 AB, Netherlands

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Bergen, 5021, Norway

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Oslo, NO 0450, Norway

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Olsztyn, 10226, Poland

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Gyeonggi-do, Korea, 10408, South Korea

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Seoul, Korea, 03080, South Korea

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Seoul, Korea, 05505, South Korea

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Seoul, 03722, South Korea

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Elche, Alicante, 03203, Spain

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Madrid, 28041, Spain

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Related Publications (1)

• Di Leo A, Johnston S, Lee KS, Ciruelos E, Lonning PE, Janni W, O'Regan R, Mouret-Reynier MA, Kalev D, Egle D, Csoszi T, Bordonaro R, Decker T, Tjan-Heijnen VCG, Blau S, Schirone A, Weber D, El-Hashimy M, Dharan B, Sellami D, Bachelot T. Buparlisib plus fulvestrant in postmenopausal women with hormone-receptor-positive, HER2-negative, advanced breast cancer progressing on or after mTOR inhibition (BELLE-3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2018 Jan;19(1):87-100. doi: 10.1016/S1470-2045(17)30688-5. Epub 2017 Dec 7.

  PMID: 29223745 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis; Hereditary Sensory and Autonomic Neuropathies

Interventions

Fulvestrant; 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)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Limitations and Caveats

The primary efficacy analysis was completed by 23May16 (primary PFS analysis cutoff date). The study was later terminated and the final safety analysis was conducted up to 08Sep17. One CRF was collecting on 21Sep2017 for survival follow up (LPLV).

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@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 3
• 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: June 29, 2012
• First Posted: July 4, 2012
• Study Start: October 3, 2012
• Primary Completion: May 23, 2016
• Study Completion: September 21, 2017
• Last Updated: January 30, 2019
• Results First Posted: January 9, 2019

Record last verified: 2019-01

Locations

GR (8); AU (4); LE (3); AR (4); FI (1); NO (2); DE (22); SE (3); CO (2); BU (7); PL (1); ES (24); HU (4); TH (1); BE (4); KR (4); GB (7); NL (8); IT (38); US (37); CA (2); FR (11)