BKM120 in Metastatic Castration-resistant Prostate Cancer

• Register: ClinicalTrials.gov
• Last refreshed on: 22 April 2013
• Main ID: NCT01385293
• Date of registration: 28/06/2011
• Primary sponsor: Andrew J. Armstrong
• Public title: BKM120 in Metastatic Castration-resistant Prostate Cancer
• Scientific title: Phase II Study of BKM120 in Men With Metastatic Castration-Resistant Prostate Cancer
• Date of first enrolment: August 2011
• Target sample size: 66
• Recruitment status: Recruiting
• URL: http://clinicaltrials.gov/show/NCT01385293
• Study type: Interventional
• Study design: Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Countries of recruitment

United States

Contacts

• Name: Carol Winters, RN

• Name: Andrew Armstrong, MD, ScM
• Affiliation: Duke Cancer Institute

Key inclusion & exclusion 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 registration) 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 registration

- Have undergone major surgery = 4 weeks prior to starting study drug or who have not
recovered from side effects of such therapy prior to registration

- 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



Age minimum: 18 Years
Age maximum: N/A
Gender: Male

Health Condition(s) or Problem(s) studied

Metastatic (Spread to Other Areas of the Body)

Prostate Cancer

Intervention(s)

Drug: BKM120

Primary Outcome(s)

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 Outcome(s)

Circulating tumor cell collection, with measurements of CTC gene expression to assess mechanisms of resistance to BKM120 [Time Frame: 2 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]

Define radiologic response rates using Response Evaluation Criteria In Solid Tumors(RECIST) 1.1. [Time Frame: 2 years]

Determine the overall survival of participants. [Time Frame: 5 years]

Determine the time to new metastatic disease from the baseline visit. [Time Frame: 5 years]

Evaluate baseline circulating tumor cell (CTC) levels and changes in CTC. [Time Frame: 2 years]

Number and Percent of Participants with Adverse Events as a Measure of Safety and Tolerability [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]

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]

Prostate Specific Antigen (PSA) response [Time Frame: 2 years]

Secondary ID(s)

Pro00027410

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Novartis Pharmaceuticals