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 (BELLE-3)
This study is currently recruiting participants.
Verified May 2013 by Novartis
Sponsor:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01633060
First received: June 29, 2012
Last updated: May 10, 2013
Last verified: May 2013
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Purpose
This study will evaluate whether the addition of daily BKM120 to fulvestrant is effective and safe in treating patients with HR+, HER2-, AI treated locally advanced or metastatic breast cancer who progressed on or after mTor inhibitor based treatment.
| Condition | Intervention | Phase |
|---|---|---|
|
Metastatic Breast Cancer HR+, HER2- |
Drug: Fulvestrant Drug: BKM120 Drug: BKM120 matching placebo |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, 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 AI Treated, Locally Advanced or Metastatic Breast Cancer Who Progressed on or After mTOR Inhibitor Based Treatment |
Resource links provided by NLM:
Further study details as provided by Novartis:
Primary Outcome Measures:
- Progression Free Survival (PFS) [ Time Frame: Up to approx. 5.5 months ] [ Designated as safety issue: No ]PFS is defined as time from date of randomization to the date of the event, defined as the first radiologically documented disease progression or death due to any cause. PFS is based on local investigator assessment. Patients will be followed up for the duration of the study and for an expected average of every 8 weeks after randomization.
Secondary Outcome Measures:
- Overall survival (OS) [ Time Frame: Up to approx. 21 months ] [ Designated as safety issue: No ]Time from date of randomization to the date of death from any cause. Patients will be 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) [ Time Frame: Up to approx. 5.5 months ] [ Designated as safety issue: No ]Proportion of patients with best overall response of complete response (CR) or partial response (PR). ORR will be assessed according to RECIST 1.1 criteria. Patients will be followed up for the duration of the study and for an expected average of every 8 weeks after randomization.
- Clinical benefit rate (CBR) [ Time Frame: Up to approx. 5.5 months ] [ Designated as safety issue: No ]Proportion of patients with best overall response of complete response (CR) or partial response (PR). ORR will be assessed according to RECIST 1.1 criteria. Patients will be followed up for the duration of the study and for an expected average of every 8 weeks after randomization.
- Type, frequency and severity of adverse events [ Time Frame: at minimum at each study visit and up to approx. 8 months ] [ Designated as safety issue: Yes ]Safety will be determine by type, frequency and severity of adverse events per CTCAEv4.03 and Type, frequency and severity of laboratory toxicities per CTCAEv4.03. Patients will be followed up for the duration of the study.
- Plasma concentration-time profiles of BKM120 - pharmacokinetics (PK) [ Time Frame: C1D1, C1D15, C2D1,C3D1 and C4D1 (a cycle [C] = 4 weeks), D = Day ] [ Designated as safety issue: No ]Plasma concentration-time profiles of BKM120 and appropriate individual PK parameters.
- Patient reported outcome for global health status/QoL [ Time Frame: C1D1, C2D15, C4D1, then every 8 weeks until discontinuation (a cycle [C] = 4 weeks). ] [ Designated as safety issue: No ]Time to definitive deterioration in the global health status/QoL scale score. Change from baseline in the global health status/QOL scale score. Patients will be assessed up to approx. 5.5 months.
| Estimated Enrollment: | 615 |
| Study Start Date: | October 2012 |
| Estimated Study Completion Date: | October 2016 |
| Estimated Primary Completion Date: | October 2016 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: BKM120 and fulvestrant
BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol.
|
Drug: Fulvestrant
Intramuscular fulvestrant 500 mg (cycle 1 days 1 & 15 and once every cycle thereafter)
Drug: BKM120
BKM120 100 mg once daily
|
|
Active Comparator: Placebo and fulvestrant
BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol.
|
Drug: Fulvestrant
Intramuscular fulvestrant 500 mg (cycle 1 days 1 & 15 and once every cycle thereafter)
Drug: BKM120 matching placebo
BKM120 matching placebo, once daily
|
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Postmenopausal women
- Breast cancer that is locally advanced or metastatic
- HER2 negative disease, and a known positive hormone receptor status (common breast cancer classification tests)
- A tumor sample must be shipped to a central lab for identification of biomarkers (PI3K activation status) before randomization
- Prior treatment with AIs
- 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
Exclusion Criteria:
- More than 1 prior chemotherapy given for locally advanced or metastatic disease
- Previous treatment with PI3K inhibitors, AKT inhibitors or fulvestrant
- Symptomatic CNS metastases
- Concurrent malignancy or malignancy within 3 years prior to start of study treatment
- Certain drugs or radiation within 2-4 weeks of enrollment
- Increasing or chronic treatment (> 5 days) with corticosteroids or another immunosuppressive agent
- Active heart (cardiac) disease or a history of cardiac dysfunction as defined in the protocol
- HyperSsensitivity to fulvestrant treatment excipients
- Certain scores on an anxiety and depression mood questionnaire given at screening
- Other protocol defined criteria may apply
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01633060
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Contacts
| Contact: Novartis Pharmaceuticals | 1-888-669-6682 | |
| Contact: Novartis Pharmaceuticals |
Show 192 Study LocationsSponsors and Collaborators
Novartis Pharmaceuticals
Investigators
| Study Director: | Novartis Pharmaceuticals | Novartis Pharmaceuticals |
More Information
No publications provided
| Responsible Party: | Novartis ( Novartis Pharmaceuticals ) |
| ClinicalTrials.gov Identifier: | NCT01633060 History of Changes |
| Other Study ID Numbers: | CBKM120F2303, 2012-002571-34 |
| Study First Received: | June 29, 2012 |
| Last Updated: | May 10, 2013 |
| Health Authority: | United States: Food and Drug Administration Austria: Agency for Health and Food Safety Belgium: Federal Agency for Medicinal Products and Health Products Canada: Health Canada Czech Republic: State Institute for Drug Control Denmark: Danish Health and Medicines Authorities Spain: Spanish Agency of Medicines France: ANSM - French Health Products Safety Agency Germany: Federal Institute for Drugs and Medical Devices Hungary: National Institute of Pharmacy Netherlands: The Central Committee on Research Involving Human Subjects (CCMO) Italy: National Institute of Health Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products United Kingdom: Medicines and Healthcare Products Regulatory Agency Russia: Ministry of Health of the Russian Federation |
Keywords provided by Novartis:
|
BKM120 fulvestrant breast cancer metastatic locally advanced |
AI treated mTOR inhibitor PI3K PIK3CA PTEN |
Additional relevant MeSH terms:
|
Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Sirolimus Everolimus Fulvestrant Estradiol Antibiotics, Antineoplastic Antineoplastic Agents Therapeutic Uses Pharmacologic Actions |
Antifungal Agents Anti-Infective Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Anti-Bacterial Agents Estrogen Antagonists Estrogen Receptor Modulators Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Antineoplastic Agents, Hormonal Estrogens Hormones |
ClinicalTrials.gov processed this record on May 19, 2013