This trial is active, not recruiting.

Conditions prostate cancer, metastatic (spread to other areas of the body)
Treatment bkm120
Phase phase 2
Target PI3K
Sponsor Andrew J. Armstrong, MD
Collaborator Novartis Pharmaceuticals
Start date August 2011
End date February 2016
Trial size 66 participants
Trial identifier NCT01385293, Pro00027410


The purpose of this study is to evaluate the effects of the study drug, BKM120. The study drug, BKM120, is an inhibitor of a protein called phosphatidyl inositol-3-kinase (PI3K). This protein is found in normal cells and in cancer cells, but often in many cancer cells this protein is overactive. Inhibiting the protein may slow the growth of prostate cancer but this has not been tested yet in men with prostate cancer.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
BKM120 at 100mg orally daily
bkm120 BKM-120
BKM120 at the maximum tolerated dose (MTD) of 100mg orally daily

Primary Outcomes

Progression free survival (PFS) as determined radiographically based on Prostate Cancer Working Group 2 (PCWG2) criteria or based on the onset of a skeletal related event.
time frame: 5 years

Secondary Outcomes

Define radiologic response rates using Response Evaluation Criteria In Solid Tumors(RECIST) 1.1.
time frame: 2 years
Number and Percent of Participants with Adverse Events as a Measure of Safety and Tolerability
time frame: 2 years
Prostate Specific Antigen (PSA) response
time frame: 2 years
Determine the overall survival of participants.
time frame: 5 years
Evaluate baseline circulating tumor cell (CTC) levels and changes in CTC.
time frame: 2 years
Determine the time to new metastatic disease from the baseline visit.
time frame: 5 years
Correlation of baseline genomic profile from targeted metastatic biopsy with PFS, evaluating known oncogenic signatures, particularly the PI3 kinase signature and presence or absence of phosphatase and tensin homolog (PTEN) and PI3K activation.
time frame: 2 years
Post‐treatment day 28 (optional) metastatic biopsy to assess inhibition of the PI3K/Akt pathway, correlated with a day 28 serum pharmacokinetic assessment
time frame: 2 years
Circulating tumor cell collection, with measurements of CTC gene expression to assess mechanisms of resistance to BKM120
time frame: 2 years
Post‐treatment day 28 (optional) metastatic biopsy gene expression profile to assess mechanisms of resistance to BKM120
time frame: 2 years

Eligibility Criteria

Male participants at least 18 years old.

Inclusion Criteria: - Age ≥ 18 years - Karnofsky performance status ≥ 70 - Life expectancy of ≥ 12 weeks as determined by treating investigator - Adequate laboratory parameters - Histologically confirmed diagnosis of adenocarcinoma of the prostate. Histologic variants of prostate cancer, including neuroendocrine features and small cell carcinoma of the prostate are permitted - Radiographic evidence of metastatic disease - Evidence of disease progression on androgen deprivation therapy (ADT) - A minimum of 4 weeks elapsed off of antiandrogen therapy prior to registration (i.e. flutamide, nilutamide) and 6 weeks for bicalutamide, without evidence of an anti-androgen withdrawal response. Patients who did not have a PSA decline with the most recent antiandrogen therapy require only a 2 week washout period prior to registration - A minimum of 2 weeks from prior abiraterone acetate, sipuleucel-T, MDV3100, orteronel (TAK700), ketoconazole, or other experimental anti-cancer therapies prior to registration is required. Concomitant treatment with enzalutamide is permitted. - At least one prior systemic chemotherapy regimen FDA approved for metastatic prostate cancer - A minimum of 4 weeks from any major surgery prior to registration Exclusion Criteria: - Have received prior treatment with a PI3K inhibitor - Known hypersensitivity to BKM120 or to its excipients - Untreated brain metastases - Patients with hepatitis B or C, other acute or chronic liver disease, or a recent (within 12 months of administration of first dose of study drug) history of pancreatitis - Patients with certain mood disorders as judged by the investigator or a psychiatrist - History of treatment in an inpatient psychiatric setting - Concurrent severe and/or uncontrolled cardiac conditions which could compromise participation in the study - Other concurrent severe and/or uncontrolled concomitant medical conditions that could cause unacceptable safety risks or compromise compliance with the protocol - Uncontrolled diabetes mellitus defined as a fasting plasma glucose level of >120. - Diarrhea ≥ CTCAE grade 2 - Drugs or substances known to be strong inhibitors or inducers of the isoenzyme CYP3A4 should be avoided as systemic therapy in association with BKM120 as these can alter its metabolism. Topical use of creams or other applications not absorbed into the circulation is permitted - Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BKM120 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection) - Have been treated with any granulocyte colony-stimulating growth factors (e.g., G-CSF, GM-CSF) ≤ 2 weeks prior to starting study drug. Erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to enrollment, may be continued - Currently receiving treatment with medication that has the potential to significantly prolong the QT interval or induce Torsades de Pointes, and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug - Have received immunosuppressive therapy including corticosteroids ≤ 2 weeks prior to starting study drug. Prednisone at a total daily dose of 10 mg orally or its equivalent is permitted, if initiated at least 2 weeks prior to enrollment - History of solid organ or stem cell transplantation - Have received wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy prior to administration of first dose of study drug - Have undergone major surgery ≤ 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy prior to administration of first dose of study drug - Currently taking therapeutic doses of warfarin sodium or any other coumadin-derivative anticoagulant - Known diagnosis of human immunodeficiency virus (HIV) infection - History of another malignancy within 3 years, except cured basal cell or squamous cell carcinoma of the skin or low grade papillary bladder cancer Other inclusion and exclusion criteria apply

Additional Information

Official title Phase II Study of BKM120 in Men With Metastatic Castration-Resistant Prostate Cancer
Principal investigator Andrew Armstrong, MD, ScM
Description This is an open label, single arm phase II study of BKM120 in men with metastatic castration resistant prostate cancer (CRPC) who have progressed on or following completion of docetaxel-based chemotherapy. Prior progression on cabazitaxel, provenge, abiraterone, or enzalutamide (MDV3100) is also permitted. Patients must have baseline evaluations performed prior to the first dose of study drug and must meet all inclusion and exclusion criteria. Results of the baseline evaluations, which assure that all inclusion and exclusion criteria have been satisfied, must be reviewed by the Principal Investigator or his/her designee prior to enrollment of that patient. In addition, the patient must be thoroughly informed about all aspects of the study, including the study visit schedule and required evaluations and all regulatory requirements for informed consent. The written informed consent must be obtained from the patient prior to protocol-specific screening tests. The following criteria apply to all patients enrolled onto the study unless otherwise specified.
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by Duke University.