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
- Conditions
- Metastatic Breast Cancer
- Interventions
- Registration Number
- NCT01633060
- Lead Sponsor
- Novartis Pharmaceuticals
- 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).
- Detailed Description
Novartis decided not to pursue further development of buparlisib program. On 19 Dec 2016, Novartis notified the Investigators about this decision; accordingly the CBKM120F2303 study was terminated.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- Female
- Target Recruitment
- 432
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description BKM120 100mg + Fulvestrant BKM120 BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol. Placebo + Fulvestrant BKM120 matching placebo BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol. BKM120 100mg + Fulvestrant Fulvestrant BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol. Placebo + Fulvestrant Fulvestrant BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol.
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS) Based on Local Investigator Assessment - Full Analysis Set (FAS) Every 6 weeks after randomization up to a maximum of 4 years 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.
- Secondary Outcome Measures
Name Time Method Progression Free Survival (PFS) by PIK3CA Mutational Status Every 6 weeks after randomization up to a maximum of 5 years 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.
Overall Response Rate (ORR) by PIK3CA Mutational Status Every 6 weeks after randomization up to a maximum of 5 years Overall Response Rate (ORR) is defined as the proportion of participants with best overall response of complete response (CR) or partial response (PR) based on local investigator's assessment according to RECIST 1.1. ORR was analyzed in the full population and by PIK3CA mutational status based on ctDNA. Response Evaluation Criteria in Solid Tumors (RECIST v1.1) for target/non target lesions: Complete Response (CR), disappearance of all target/non target lesions (all lymph nodes assigned as non-target lesions must be non-pathological in size (\< 10 mm short axis)); Partial response (PR), \>=30% decrease in the sum of the longest diameter of target lesions ; Overall Response (OR)= CR+PR. Patients were followed up for the duration of the study and for approximately every 6 weeks after randomization.
Clinical Benefit Rate (CBR) by PIK3CA Mutational Status Week 14, Week 24 Clinical Benefit Rate (CBR) is defined as the proportion of participants with a best overall response of complete response (CR) or partial response (PR) or stable disease (SD) or Non-CR/non-PD lasting more than 14 or 24 weeks based on local investigator's assessment according to RECIST 1.1. CBR was analyzed in the full population and by PIK3CA mutational status based on ctDNA. Patients were followed up for the duration of the study and approximately every 6 weeks after randomization.
Overall Survival (OS) - Full Analysis Set (FAS) Every 6 weeks after randomization up to a maximum of 5 years Overall Survival (OS) is defined as the time from date of randomization to date of death due to any cause. If a patient was not known to have died by the date of analysis cut-off, OS was censored at the date of last known date patient alive. Patients were followed up approximately every 6 weeks after randomization and every 3 months during survival follow-up.
Long-term Safety and Tolerability in the Two Treatment Arms - Safety Set (SS) From first dose of study treatment to 30 days after last dose of study treatment, up to 5 years Analysis of frequencies for treatment emergent Adverse Event (AE), Serious Adverse Event (SAE) and Deaths.
Health-related Quality of Life (HRQoL):Time to 10% Definitive Deterioration in the Global Health Status/Quality of Life Per EORTC-QLQ-C30 - Full Analysis Set (FAS) Baseline, Week 6 (C2D15), Week 12 (C4D1), then every 8 weeks until discontinuation (a cycle [C] = 4 weeks) up to 5 years. The global health status/QoL scale score of the QLQ-C30 is identified as the primary PRO variable of interest. Physical Functioning (PF), Emotional Functioning (EF) and Social Functioning (SF) scale scores of the QLQ-C30. The time to definitive 10% deterioration is defined as the time from the randomization date to the date of an event, which is defined as a worsening (decrease) in score by at least 10% compared to baseline, with no later increase above this threshold observed during the course of the study or death due to any cause. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. A high score for a functional scale represents a high /healthy level of functioning, a high score for the global health status / QoL represents a high QoL.
Overall Survival (OS) by PIK3CA Mutational Status Every 6 weeks after randomization up to a maximum of 5 years Overall Survival (OS) by PIK3CA mutational status based on ctDNA is defined as the time from date of randomization to date of death due to any cause. If a patient was not known to have died by the date of analysis cut-off, OS was censored at the date of last known date patient alive. Patients were followed up approximately every 6 weeks after randomization and every 3 months during survival follow-up.
Predose Trough Concentration-time Profile of BKM120 in Combination With Fulvestrant Over Time - Pharmacokinetic Analysis Set (PAS) C1D15, C2D1, C3D1 and C4D1 Pre-dose samples were collected for trough concentrations at Cycle 1 Day 15, Cycle 2 Day 1, Cycle 3 Day 1 and Cycle 4 Day 1.
Plasma Concentration-time Profiles of BKM120 in Combination With Fulvestrant at Cycle 1 Day 1 - Pharmacokinetic Analysis Set (PAS) C1D1 1 hour post dose, C1D1 2 hour post dose, C1D1 6 hour post dose and C1D1 9 hour post dose Plasma samples were collected from the first 100 BKM120-treated patients on Cycle 1 Day 1 (at 1h, 2h, and 6h post-dose and a recommended 9h post-dose sample).
Time to Definitive Deterioration of ECOG Performance Status From Baseline - Full Analysis Set (FAS) Screening, Baseline (Cycle 1 Day 1) and then at day 1 of each cycle and at the EOT visit The Eastern Cooperative Oncology Group (ECOG) Performance Status is a scale used to assess how a patient's disease is progressing, assess how the disease affects the daily living abilities of the patient, and determine appropriate treatment and prognosis. The ECOG Performance Scores has 5 grades: 0 = fully active, able to carry on all pre-disease performance without restriction, 1 = restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework, office work, 2 = ambulatory and capable of all self-care but unable to carry out any work activities, up and about more than 50% of waking hours, 3 = capable of only limited self-care, confined to bed or chair more than 50% of waking hours, 4 = completely disabled, cannot carry on any self-care, totally confined to bed or chair and 5 = dead. Definitive deterioration is defined as no improvement in the ECOG status following observation of the deterioration.
Trial Locations
- Locations (38)
University of Maryland Medical Center Univ Maryland
🇺🇸Baltimore, Maryland, United States
The Methodist Hospital Cancer Center
🇺🇸Houston, Texas, United States
Los Angeles Hematology/Oncology Medical Group Onc Dept.
🇺🇸Los Angeles, California, United States
Ironwood Cancer and Research Centers SC
🇺🇸Chandler, Arizona, United States
University of South Alabama / Mitchell Cancer Institute Univ South AL
🇺🇸Mobile, Alabama, United States
Cedars Sinai Medical Center SC-5
🇺🇸Los Angeles, California, United States
University of California at Los Angeles UCLA SC
🇺🇸Los Angeles, California, United States
Emory University School of Medicine/Winship Cancer Institute Emory
🇺🇸Atlanta, Georgia, United States
Edward Hospital Edward Hospital
🇺🇸Naperville, Illinois, United States
Morristown Memorial Hospital Morristown Mem
🇺🇸Morristown, New Jersey, United States
CINJ at Cooper University Hospital Dept of Onc
🇺🇸Voorhees, New Jersey, United States
Montefiore Medical Center Montefiore
🇺🇸Bronx, New York, United States
Clinical Research Alliance BKM120F2303
🇺🇸Lake Success, New York, United States
University of Pittsburgh Cancer Institute Dept of Magee Women's Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Texas Oncology PA Dallas Presbyterian Hospital SC
🇺🇸Dallas, Texas, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
US Oncology, P.A.
🇺🇸Tyler, Texas, United States
Northwest Medical Specialties
🇺🇸Tacoma, Washington, United States
Novartis Investigative Site
🇬🇧Nottingham, United Kingdom
Compassionate Cancer Care Medical Group CCCMG
🇺🇸Fountain Valley, California, United States
Highlands Oncology Group
🇺🇸Fayetteville, Arkansas, United States
Pacific Cancer Care
🇺🇸Monterey, California, United States
University Cancer & Blood Center, LLC
🇺🇸Athens, Georgia, United States
Crescent City Research Consortium, LLC SC
🇺🇸Metairie, Louisiana, United States
Mercy Medical Research Institute SC
🇺🇸Manchester, Missouri, United States
Clinical Research Alliance
🇺🇸Lake Success, New York, United States
The West Clinic Dept. of the West Clinic
🇺🇸Memphis, Tennessee, United States
Texas Oncology P A SC-Austin
🇺🇸Dallas, Texas, United States
Texas Oncology P A Texas Oncology - Fort Worth (3
🇺🇸Dallas, Texas, United States
Texas Oncology Texas Oncology - Sammons
🇺🇸Dallas, Texas, United States
Texas Tech University Health Science Center Dept of Texas Tech
🇺🇸El Paso, Texas, United States
Rocky Mountain Cancer Centers SC
🇺🇸Denver, Colorado, United States
Northwest Cancer Specialists Compass Oncology -BKM
🇺🇸Portland, Oregon, United States
Oregon Health and Science University SC-5
🇺🇸Portland, Oregon, United States
Moanalua Medical Center. Attn: Oncology Dept
🇺🇸Honolulu, Hawaii, United States
Lsu Health Sciences Center/ Lsu School of Medicine Lsu
🇺🇸New Orleans, Louisiana, United States
John Ochsner Heart and Vascular Institute Clinical Trials Ochsner 2
🇺🇸New Orleans, Louisiana, United States
LSU Health Sciences Center Feist-Weiller Cancer Center
🇺🇸New Orleans, Louisiana, United States