Neoadjuvant BKM120 in High-risk Prostate Cancer

NCT01695473 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 115516NCI-2013-01830
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase II, study of BKM120 in patients with high-risk, localized prostate cancer. Eligible patients will be enrolled and scheduled to have an ultrasound-guided biopsy of the prostate to confirm high-risk disease and collect prostate tissue for analysis. Two weeks after the biopsy, patients will begin taking 100 mg/day of BKM120. BKM120 will be given at this dose level orally once daily for 14 days prior to radical prostatectomy at University of California, San Francisco. Radical prostatectomy will be performed on the day of the last dose of BKM120 at day 14. No further drug will be tken after the radical prostatectomy.

Conditions

High Risk Prostate Cancer

Keywords

Prostate cancer; High-risk prostate cancer; Radical prostatectomy; BKM120

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Decrease in Phosphorylated S6 Immunohistochemistry (ICH) From Baseline

  Percentage of men with downstream target inhibition of PI3K in prostate tumor tissue as measured by phosphorylated S6 immunohistochemistry (ICH) when treated with 100 mg/day of BKM120 using paired tumor biopsies from before and after drug administration and defined as ≥ 60% decrease in phosphorylated S6 (pS6) from baseline by Immunohistochemistry (IHC).

  Up to 3 months

Secondary Outcomes (3)

• Percentage of Participants With Decrease in 4E-binding protein1 (p4EBP1) Protein Phosphorylation From Baseline

  Up to 3 months

• Percentage of Participants With Decrease in AKT Protein From Baseline

  Up to 3 months

• Number of Participants Displaying Activity of Short Term BKM120 Administration

  1 Day, immediately prior to surgery

Study Arms (1)

Neoadjuvant BKM120

EXPERIMENTAL

Two weeks after confirmatory biopsy, patients will begin taking 100 mg/day of BKM120. BKM120 will be given at this dose level orally once daily for 14 days prior to radical prostatectomy. Radical prostatectomy will be performed on the day of the last dose of BKM120 at day 14. No further drug will be administered after radical prostatectomy. For unforeseen delays in operating room (OR) scheduling, up to 7 additional days of BKM120 may be administered prior to surgery.

Drug: BKM120

Interventions

BKM120 DRUG

Two weeks after confirmatory biopsy, patients will begin taking 100 mg/day of BKM120. BKM120 will be given at this dose level orally once daily for 14 days prior to radical prostatectomy. Radical prostatectomy will be performed on the day of the last dose of BKM120 at day 14. No further drug will be administered after radical prostatectomy. For unforeseen delays in OR scheduling, up to 7 additional days of BKM120 may be administered prior to surgery.

Also known as: Buparlisib

Neoadjuvant BKM120

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed adenocarcinoma of the prostate
• Candidate for radical prostatectomy
• Prostate cancer with the following pathological characteristics:
• Gleason sum \> 8 AND at least 2 discrete core biopsies containing a minimum of 20% cancer or,
• Gleason pattern 4 + 3 = 7 and greater than 50% of biopsies positive for prostate cancer
• Age \>= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status \> 2
• Ability to take oral medications (capsule must be swallowed with liquid)
• Adequate bone marrow function as shown by: Absolute Neutrophil Count (ANC) \>= 1.5 x 109/liter, Platelets ≥ 100 x 109/L, Hemoglobin \> 9 grams(g) /decilitre(dL)
• Total calcium (corrected for serum albumin) within normal limits (biphosphonate use for malignant hypercalcemia control is not allowed)
• Magnesium \>= the lower limit of normal
• Potassium within normal limits for the institution
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal range
• Serum bilirubin within normal range (or total bilirubin \<= 3.0 x upper limit of normal (ULN) with direct bilirubin within normal range in patients with well documented Gilbert Syndrome)
• Serum creatinine \<= 1.5 x upper limit of normal (ULN) or 24-hour clearance \>= 50 milliliter per min (mL/min)

You may not qualify if:

• Prior treatment with a phosphatidylinositol 3-kinase (PI3K) inhibitor
• Known hypersensitivity to BKM120 or to its excipients
• History of another malignancy within 3 years, except cured basal cell carcinoma of the skin
• Hormonal therapy with Gonadotropin-releasing hormone (GnRH) agonists, GnRH antagonists or high dose bicalutamide within 1 month of enrollment unless serum testosterone is within normal limits.
• Following mood disorders as judged by the investigator and/or symptom management service co-investigator, or as a result of patient's mood assessment questionnaire:
• Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others)
• Current \>= NCI Common Terminology Criteria for Adverse Events (CTCAE) grade 3 anxiety
• Meets the cut-off score of \>= 10 in the Patient Health Questionnaire (PHQ-9) or a cut-off of \>= 15 in the Generalized Anxiety Disorder (GAD-7) mood scale, respectively, or selects a positive response of "1, 2, or 3" to question number 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of the total score of the PHQ-9) will be excluded from the study
• Current diarrhea \>= CTCAE grade 2
• Active cardiac disease including any of the following:
• History of left ventricular ejection fraction (LVEF) \< 50% as determined by Multiple Grated acquisition (MUGA) scan or echocardiogram (ECHO)
• QTc \> 450 msec on screening electrocardiogram (ECG (using the QTcF formula)
• Angina pectoris that requires the use of anti-anginal medication
• History of ventricular arrhythmias except for benign premature ventricular contractions
• Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication

Sponsors & Collaborators

• Won Kim: lead
• Novartis: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

NVP-BKM120

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Limitations and Caveats

The study was closed early due to low accrual.

Results Point of Contact

• Title: Dr. Won Kim, MD
• Organization: University of California, San Francisco

Won.Kim@ucsf.edu

877-827-3222

Study Officials

• Won Kim, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prinicipal Investigator

Study Record Dates

• First Submitted: September 26, 2012
• First Posted: September 28, 2012
• Study Start: April 23, 2013
• Primary Completion: February 5, 2015
• Study Completion: February 5, 2015
• Last Updated: January 13, 2021
• Results First Posted: January 13, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)