Phase III Study of BKM120/Placebo With Fulvestrant in Postmenopausal Patients With Hormone Receptor Positive HER2-negative Locally Advanced or Metastatic Breast Cancer Refractory to Aromatase Inhibitor (BELLE-2)
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| ClinicalTrials.gov Identifier: NCT01610284 |
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Recruitment Status :
Completed
First Posted : June 4, 2012
Results First Posted : June 18, 2020
Last Update Posted : August 25, 2020
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Sponsor:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
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Brief Summary:
This study was a multi-center, randomized, double-blind, placebo controlled Phase III study to determine the efficacy and safety of treatment with buparlisib plus fulvestrant versus fulvestrant plus placebo in postmenopausal women with hormone Receptor-positive (HR-positive), human epidermal growth factor receptor 2-negative (HER2-negative), locally advanced or metastatic breast cancer (MBC) whose disease has progressed on or after aromatase inhibitor (AI) treatment.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Breast Cancer | Drug: Fulvestrant Drug: BKM120 Drug: BKM120 matching placebo | Phase 3 |
Patients were randomized (1:1) to receive buparlisib (100 mg/day) or placebo with fulvestrant (500 mg); randomization was stratified by PI3K pathway activation status (activated, non-activated, unknown determined in archival tumor tissue) and visceral disease status (present or absent). Tumor evaluation was performed 6 weeks after the randomization date and then every 8 weeks until radiological progression (based on Response Evaluation Criteria In Solid Tumors [RECIST] version 1.1).
Novartis made the decision not to pursue further development of buparlisib and to terminate the ongoing studies in the program. Accordingly, on 19-Dec-2016, Novartis notified all the Investigators about the decision not to pursue further development of buparlisib in Breast Cancer. As a result, the CBKM120F2302 study was terminated on 19-Apr-2019 (last subject last visit).
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 1147 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase III Randomized, Double Blind Placebo Controlled Study of BKM120 With Fulvestrant, in Postmenopausal Women With Hormone Receptor-positive HER2-negative Locally Advanced or Metastatic Breast Cancer Which Progressed on or After Aromatase Inhibitor Treatment |
| Actual Study Start Date : | August 7, 2012 |
| Actual Primary Completion Date : | April 29, 2015 |
| Actual Study Completion Date : | April 19, 2019 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Breast cancer
Drug Information
available for:
Fulvestrant
| Arm | Intervention/treatment |
|---|---|
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Experimental: BKM120 100mg + Fulvestrant
BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol.
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Drug: Fulvestrant
Intramuscular fulvestrant 500 mg (Day 1 and Day 15 of Cycle 1 and Day 1 of every cycle thereafter) Drug: BKM120 BKM120 100 mg once daily |
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Placebo Comparator: Placebo + Fulvestrant
BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol.
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Drug: Fulvestrant
Intramuscular fulvestrant 500 mg (Day 1 and Day 15 of Cycle 1 and Day 1 of every cycle thereafter) Drug: BKM120 matching placebo BKM120 matching placebo, once daily |
Primary Outcome Measures :
- Progression Free Survival (PFS) Based on Local Investigator Assessment - Full Analysis Set (FAS) in Full Population, Main Study Cohort and PI3K Unknown Cohort [ Time Frame: Date of randomization to the date of first documented tumor progression or death from any cause, whichever occurs first, reported between day of first patient randomized up to approximately 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.
Secondary Outcome Measures :
- Overall Survival (OS) - Full Analysis Set (FAS) in Full Population, Main Study Cohort and PI3K Unknown Cohort [ Time Frame: Every 3 months following end of treatment visit, assessed for approximately 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 for the duration of the study and for an expected average of every 3 months after end of treatment.
- Overall Response Rate (ORR) - Full Analysis Set (FAS) in Full Population, Main Study Cohort and PI3K Unknown Cohort [ Time Frame: From the date of randomization until the date of the first documented disease progression or date of death from any cause whichever came first, assessed for approximately 5 years ]Overall Response Rate (ORR) is defined as the percentage 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. 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. Only descriptive analysis performed.
- Clinical Benefit Rate (CBR) - Full Analysis Set (FAS) in Full Population, Main Study Cohort and PI3K Unknown Cohort [ Time Frame: From the date of randomization until the date of the first documented disease progression or date of death from any cause whichever came first, assessed for approximately 5 years ]Clinical Benefit Rate (CBR) is defined as the percentage 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 24 weeks based on local investigator's assessment according to RECIST 1.1. CBR was analyzed in the full population. Only descriptive analysis performed.
- Number of Participants With On-Treatments Adverse Events, Serious Adverse Events and Deaths [ Time Frame: From first dose of study treatment to 30 days after last dose of study treatment, assessed for approximately 5 years ]Analysis of frequencies for treatment emergent Adverse Event (AE), Serious Adverse Event (SAE) and Deaths. Only descriptive analysis performed.
- Plasma Concentration-time Profiles of BKM120 in Combination With Fulvestrant at Cycle 2 Day 1 [ Time Frame: Cycle2 Day1 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 24 hours post-dose). Each cycle is 28 days. ]Plasma samples were collected from the first 200 BKM120-treated patients on Cycle 2 Day 1 (at pre-dose, 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h and 24h [before Cycle 2 Day 2 dose] post-dose). Each cycle is 28 days. Only descriptive analysis performed.
- Predose Trough Concentration-time Profile of BKM120 in Combination With Fulvestrant Over Time - Pharmacokinetic Analysis Set (PAS) [ Time Frame: Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3 Day 1. Each cycle is 28 days. ]Pre-dose samples were collected for trough concentrations at Cycle 2 Day 1, Cycle 2 Day 15 and Cycle 3 Day 1. Each cycle is 28 days. Only descriptive analysis performed.
- Median Time to Definitive Deterioration of the ECOG Performance Status - Full Analysis Set (FAS) [ Time Frame: Up to approx 27 months ]Time to definitive deterioration of the ECOG PS was defined as the time between the date of randomization and the date of the assessment at which definitive deterioration was seen. Only descriptive analysis performed.
- Health-related Quality of Life (HRQoL):Time to 10% Definitive Deterioration in the Global Health Status/Quality of Life Per EORTC-QLQ-C30 [ Time Frame: Cycle 1 day 1, cycle 1 day 15, 6 weeks after randomisation and then every 8 weeks until end of treatment ]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. Patients were assessed up to approx. 8.3 months. Only descriptive analysis performed.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
Criteria
Key Inclusion Criteria:
- Locally advanced or metastatic breast cancer
- HER2-negative and hormone receptor-positive status (common breast cancer classification tests)
- Postmenopausal woman
- A tumor sample must be shipped to a Novartis designated laboratory for identification of biomarkers (PI3K activation status)
- Progression or recurrence of breast cancer while on or after aromatase inhibitor treatment
- Measurable disease or non measurable disease bone lesions in the absence of measurable disease as per RECIST 1.1
- Adequate bone marrow and organ function defined by laboratory values
Key Exclusion Criteria:
- Previous treatment with PI3K inhibitors, AKT inhibitors, mTOR inhibitor or fulvestrant
- More than one prior chemotherapy line for metastatic disease
- Symptomatic brain metastases
- Increasing or chronic treatment (> 5 days) with corticosteroids or another immunosuppressive agent
- Active heart (cardiac) disease as defined in the protocol
- Certain scores on an anxiety and depression mood questionnaires
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01610284
Locations
Show 268 study locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
| Study Director: | Novartis Pharmaceuticals | Novartis Pharmaceuticals |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Novartis Pharmaceuticals |
| ClinicalTrials.gov Identifier: | NCT01610284 |
| Other Study ID Numbers: |
CBKM120F2302 2011-005524-17 ( EudraCT Number ) |
| First Posted: | June 4, 2012 Key Record Dates |
| Results First Posted: | June 18, 2020 |
| Last Update Posted: | August 25, 2020 |
| Last Verified: | August 2020 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
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Breast cancer Hormone receptor positive HER2-negative Metastatic Locally advanced |
PI3K Fulvestrant Refractory Aromatase inhibitor |
Additional relevant MeSH terms:
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Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Fulvestrant Antineoplastic Agents, Hormonal |
Antineoplastic Agents Estrogen Receptor Antagonists Estrogen Antagonists Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs |