A Phase 2 interventional study of BKM120 in Breast Cancer, sponsored by Dana-Farber Cancer Institute. Completed at 4 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-01-23.
Sponsored by Dana-Farber Cancer Institute · Phase 2, Interventional, and Treatment
Triple negative breast cancer (TNBC) has an aggressive phenotype and poor prognosis. This tumor type characterized by lack of expression of estrogen receptor (ER), progesterone receptor (PR) and no amplification of the human epidermal growth factor 2 (HER2) accounts for 15% of breast cancers. Limited treatment options exist in the clinic as hormonal therapies and HER2-trageted agents have proven ineffective. BKM120 is a drug that works by blocking a protein called phosphatidylinositol-3-kinase (PI3K) which may contribute to cancer growth. This drug has been used in experiments in the laboratory and information from these research studies suggests that BKM120 may help to prevent cancer cells from growing. In this research study, the investigators are looking to see if BKM120 works to stop breast cancer cells from growing.
Study plan Two investigator-initiated protocols (one for US, one for Spain) will be enrolling in parallel. The first 50 participants will be recruited concurrently in US and Spain.
Stage 1 Stage 1 will include up to 50 participants with advanced TN disease. Available tumor block is required in all participants per inclusion criteria. Analysis of this tumor block will be used for correlation of predictive markers and clinical response in order to define potential subpopulation that benefit from BKM120. In Stage 1, all participants will have biopsies done at baseline, cycle 1 day 28/cycle 2 day 1 and end of treatment to analyze drug effect in the PI3K and mitogen-activated protein kinases (MAPK) pathway. This will aid to understand the pharmacodynamic effects of BKM120 in tumors with similar genetic background (triple negative disease). The enrollment of Stage 1 will ensure that at least 10 paired evaluable biopsies are obtained. After the enrollment of the first 29 evaluable subjects enrolled overall in Stage 1 (considering the US and the Spanish protocol), the Steering Committee will perform an interim analysis of safety and efficacy. If absolutely no activity is observed, the clinical trial will close and no more subjects will be enrolled. If there are early signs of activity (one patient or more achieving clinical benefit response), enrollment will proceed until 50 participants are enrolled in Stage 1. After 50 patients have been enrolled, we will analyze preliminary responses to treatment depending on the molecular status of each patient.
Stage 2 Were the trial to continue at the end of Stage 1, 50 participants would have been treated and their clinical status and response to therapy will be available. Also, paraffin blocks from these participants will have been analyzed for predictive markers of treatment effect. If there is clinical activity observed in Stage 1 and this analysis shows preliminary signs of response in a subpopulation based on the presence or absence of tumor PI3K pathway alterations, participant pre-selection may be implemented for Stage 2 (justified in an amendment before proceeding to Stage 2.
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This study's enrollment of 50 is below the median of 72 across 9,303 interventional studies indexed under Breast Neoplasms.
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Exclusion Criteria:
BKM120: 100 mg capsule once daily each day of a 28 day cycle . Treatment with BKM120 will continue until disease progression, unacceptable toxicity or withdrawal for other reasons.
Drug: BKM120
Also known as: Buparlisib
Clinical Benefit Rate
Clinical benefit rate (CBR) was defined as the proportion of participants achieving complete response (CR), partial response (PR), or stable disease (SD) for 4 months or longer based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PD is at least a 20% increase in sum LD of target lesions (smallest sum LD reference), new lesions, and/or unequivocal progression of existing non-target lesions. Stable disease (SD) is defined as any condition not meeting the above criteria.
Time frame: Disease was evaluated radiologically at baseline and every 2 cycles on treatment then every 3 months up to 2 years. Participants in this study cohort were followed for response on average approximately 2 months.
Progression Free Survival
Progression-free survival (PFS) based on the Kaplan-Meier (KM) method is defined as the duration of time from study entry to documented disease progression (PD) or death. Participants alive without PD are censored at the date of last disease assessment. Per RECIST 1.1 criteria: PD is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.
Time frame: Disease was evaluated radiologically at baseline and every 2 cycles on treatment then every 3 months up to 2 years. Participants in this study cohort were followed for PFS on average approximately 2 months.
Overall Survival
Overall survival (OS) is defined as the duration of time from study entry to death or date last known alive and estimated using the KM method.
Time frame: Participants were assessed every 3 months post-treatment up to 2 years. Average survival follow-up for the study cohort was 13.8 months.
Participants enrolled between June 2012 and September 2014.
| Milestone | BKM120 |
|---|---|
| Started | 50 |
| Completed | 0 |
| Not completed | 50 |
| Withdrew: Disease progression | 41 |
| Withdrew: Adverse event | 7 |
| Withdrew: Physician decision | 1 |
| Withdrew: Withdrawal by subject | 1 |
Clinical benefit rate (CBR) was defined as the proportion of participants achieving complete response (CR), partial response (PR), or stable disease (SD) for 4 months or longer based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PD is at least a 20% increase in sum LD of target lesions (smallest sum LD reference), new lesions, and/or unequivocal progression of existing non-target lesions. Stable disease (SD) is defined as any condition not meeting the above criteria.
| proportion of participants | BKM120 |
|---|---|
| Clinical Benefit Rate | 0.12 (0.056 to 0.238) |
Progression-free survival (PFS) based on the Kaplan-Meier (KM) method is defined as the duration of time from study entry to documented disease progression (PD) or death. Participants alive without PD are censored at the date of last disease assessment. Per RECIST 1.1 criteria: PD is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.
| months | BKM120 |
|---|---|
| Progression Free Survival | 1.8 (1.6 to 2.3) |
Overall survival (OS) is defined as the duration of time from study entry to death or date last known alive and estimated using the KM method.
| months | BKM120 |
|---|---|
| Overall Survival | 11.2 (6.2 to 25.0) |
Collected over Adverse events (AEs) were assessed every 2 weeks for the first 2 cycles and every cycle thereafter. Participants in this study cohort were followed for AEs on average approximately 2 months.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| BKM120 | 29/50 (58%) | 17/50 (34%) | 44/50 (88%) |
| Event | BKM120 |
|---|---|
| Alanine aminotransferase increasedInvestigations | 5/50 |
| FatigueGeneral disorders | 4/50 |
| Aspartate aminotransferase increasedInvestigations | 4/50 |
| HyperglycemiaMetabolism and nutrition disorders | 2/50 |
| Rash maculo-papularSkin and subcutaneous tissue disorders | 2/50 |
| Papulopustular rashInfections and infestations | 1/50 |
| AlkalosisMetabolism and nutrition disorders | 1/50 |
| AnorexiaMetabolism and nutrition disorders | 1/50 |
| Nervous system disorders - OtherNervous system disorders | 1/50 |
| Dry skinSkin and subcutaneous tissue disorders | 1/50 |
| Event | BKM120 |
|---|---|
| FatigueGeneral disorders | 24/50 |
| NauseaGastrointestinal disorders | 16/50 |
| HyperglycemiaMetabolism and nutrition disorders | 16/50 |
| AnorexiaMetabolism and nutrition disorders | 14/50 |
| DiarrheaGastrointestinal disorders | 9/50 |
| Alanine aminotransferase increasedInvestigations | 8/50 |
| AnxietyPsychiatric disorders | 8/50 |
| DepressionPsychiatric disorders | 7/50 |
| Psychiatric disorders - OtherPsychiatric disorders | 7/50 |
| Aspartate aminotransferase increasedInvestigations | 6/50 |
The analysis dataset is comprised of all enrolled participants.
| Age, Continuous(years) | BKM120 |
|---|---|
| Median | 53 (29 to 79) |
| Sex: Female, Male(Participants) | BKM120 |
|---|---|
| Female | 50 |
| Male | 0 |
| Region of Enrollment(Participants) | BKM120 |
|---|---|
| United States | 50 |
Plan to share: No
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Dana-Farber Cancer Institute