BKM120 in Metastatic Castration-resistant Prostate Cancer

NCT01385293 | Terminated Phase 2 Results

• 1 other identifier: Pro00027410
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 3

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.

Conditions

Prostate Cancer; Metastatic (Spread to Other Areas of the Body)

Keywords

BKM120; prostate cancer; metastatic castrate-resistant prostate cancer (mCRPC)

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS) Prostate Cancer Working Group 2 (PCWG2) Criteria or Based on the Onset of a Skeletal Related Event.

  Time in months from the start of study treatment to the date of first progression or death due to any cause. Progression was determined either radiographically using a composite of the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and Prostate Cancer Working Group 2 (PCWG2) criteria or clinically as judged from a skeletal-related event, need for change in therapy, or clinical deterioration. Patients alive who had not progressed as of the last follow-up had PFS censored at the last follow-up date. Median PFS was estimated using a Kaplan-Meier curve. Response and progression are evaluated using a combination of Response Evaluation Criteria in Solid Tumors (RECIST v1.1) and guidelines for prostate cancer endpoints developed by the Prostate Cancer Clinical Trials Working Group (PCWG2). Per RECIST, progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

  5 years

Secondary Outcomes (6)

• Radiologic Response

  2 years

• Number of Participants With Adverse Events as a Measure of Safety and Tolerability

  Up to 28 days post last study drug dose. This is the follow-up safety visit.

• Prostate Specific Antigen (PSA) Response

  2 years

• Overall Survival of Participants.

  5 years

• Change in Circulating Tumor Cell (CTC) Levels From Baseline

  2 years

Study Arms (1)

Study arm

EXPERIMENTAL

BKM120 at 100mg orally daily

Drug: BKM120

Interventions

BKM120 DRUG

BKM120 at the maximum tolerated dose (MTD) of 100mg orally daily

Also known as: BKM-120

Study arm

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Andrew J. Armstrong, MD: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (3)

Duke Cancer Institute

Durham, North Carolina, 27710, United States

Location

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

University of Washington

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms; Neoplasm Metastasis

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; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Andrew J. Armstrong, MD ScM FACP
• Organization: Duke University

andrew.armstrong@duke.edu

919 668 4667

Study Officials

• Andrew Armstrong, MD, ScM

  Duke Cancer Institute

  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: Assoc Professor of Medicine

Study Record Dates

• First Submitted: June 28, 2011
• First Posted: June 30, 2011
• Study Start: August 1, 2011
• Primary Completion: February 1, 2016
• Study Completion: February 1, 2016
• Last Updated: May 19, 2017
• Results First Posted: April 7, 2017

Record last verified: 2017-04

Locations

US (3)