Clinical trial NCT01385293: BKM120 in Metastatic Castration-resistant Prostate Cancer
Official title: Phase II Study of BKM120 in Men With Metastatic Castration-Resistant Prostate Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Prostate Cancer
Metastatic (Spread to Other Areas of the Body)
Keywords: BKM120
prostate cancer
metastatic castrate-resistant prostate cancer (mCRPC)
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Novartis Pharmaceuticals
First posted: 2011-06-30
Enrollment: 30
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression Free Survival (PFS) Prostate Cancer Working Group 2 (PCWG2) Criteria or Based on the Onset of a Skeletal Related Event.
timeFrame: 5 years
Secondary outcomes:
measure: Radiologic Response
timeFrame: 2 years
measure: Number of Participants With Adverse Events as a Measure of Safety and Tolerability
timeFrame: Up to 28 days post last study drug dose. This is the follow-up safety visit.
measure: Prostate Specific Antigen (PSA) Response
timeFrame: 2 years
measure: Overall Survival of Participants.
timeFrame: 5 years
measure: Change in Circulating Tumor Cell (CTC) Levels From Baseline
timeFrame: 2 years
measure: Time to New Metastatic Disease From the Baseline Visit
timeFrame: 5 years
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke Cancer Institute
state: North Carolina
city: Portland
country: United States
facility: OHSU Knight Cancer Institute
state: Oregon
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: Duke Cancer Institute
name: Andrew Armstrong, MD, ScM
role: PRINCIPAL_INVESTIGATOR
References: