Cabazitaxel and BKM120 in Patients With Metastatic Castrate-Resistant Prostate Cancer (mCRPC) Previously Treated With Docetaxel

NCT02035124 | Withdrawn Phase 2

• 1 other identifier: SCRI GU 79
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 3

Brief Summary

Although there have been advances in the treatment of patients with metastatic castrate-resistant prostate cancer (mCRPC), all patients eventually develop resistance to available therapy. Docetaxel is the accepted first-line agent followed by cabazitaxel in the post-docetaxel phase. In this study the investigators propose to evaluate BKM120, a PI3K inhibitor, with cabazitaxel in the treatment of patients with advanced prostate cancer.

Conditions

Advanced Prostate Cancer

Keywords

Prostate; Metastatic; Refractory; mCRPC

Outcome Measures

Primary Outcomes (2)

• Number of Subjects with Serious and Non-Serious Adverse Events

  Determine the optimal dose and safety of BKM120 given with cabazitaxel to patients with metastatic castrate-resistant prostate cancer.

  up to 24 months

• Progression Free Survival (PFS)

  time to disease progression

  every 6 weeks, up to 24 months

Secondary Outcomes (2)

• Overall Response Rate

  every 6 weeks, up to 24 months

• Overall Survival

  up to 36 months

Study Arms (1)

BKM120 and Cabazitaxel

EXPERIMENTAL

BKM 120 orally once daily; Cabazitaxel 25 mg/m2 IV every 3 weeks

Drug: BKM 120; Drug: Cabazitaxel

Interventions

BKM 120 DRUG

Also known as: BKM 120 (Buparlisib)

BKM120 and Cabazitaxel

Cabazitaxel DRUG

Also known as: Jevtana

BKM120 and Cabazitaxel

Eligibility Criteria

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

You may qualify if:

• Adenocarcinoma of the prostate confirmed histologically.
• Metastatic disease confirmed by biopsy or imaging studies.
• Patients must have received treatment with docetaxel as the only previous chemotherapy regimen. In addition, previous treatment with hormonal agents and/or immune therapy is allowed (e.g., abiraterone). (Previous treatment with MDV3100 will also be allowed.)
• Patients must be castrate-resistant (i.e. developed progression of metastases following surgical castration or during medical androgen ablation therapy) with documented castrate levels of testosterone (\<50 ng/dl).
• Patients receiving medical castration therapy with gonadotropin-releasing hormone (GnRH) analogues should continue this treatment during this study.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 to 2.
• Patient must have progressive metastatic prostate cancer by at least 1 of the following criteria:
• Soft tissue disease progression defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
• Bone scan progression defined by 2 or more new lesions on bone scan.
• Prostate specific antigen (PSA) progression is determined by a minimum of three rising PSA levels with an interval of ≥1 week between each determination. The screening PSA measurement (documenting progression) must be ≥2 ng/mL.
• Screening PSA ≥2 ng/mL.
• Adequate hematologic, renal and hepatic function:
• Adequate serum chemistries.
• Ability to swallow and retain oral medication.
• Life expectancy of ≥6 months.

You may not qualify if:

• Previous treatment with PI3K inhibitors.
• Known hypersensitivity to BKM120 or polysorbate-80 or any of the excipients or taxanes.
• Use of an investigational drug ≤21 days or 5 half-lives (whichever is shorter) prior to the first dose of BKM120. For investigational drugs for which 5 half-lives is ≤21 days, a minimum of 10 days between termination of the investigational drug and administration of BKM120 is required.
• Previous chemotherapy with any agent other than docetaxel. All patients must be ≥28 days after their most recent chemotherapy and have recovered from side effects.
• Patient has received wide field radiotherapy (including therapeutic radioisotopes such as strontium 89) ≤28 days or limited field radiation for palliation ≤7 days prior to starting study drug or has not recovered from side effects of such therapy.
• Major surgical procedures ≤28 days of beginning study drug, or minor surgical procedures ≤7 days. No waiting required following port-a-cath placement.
• Clinical significant peripheral neuropathy (defined as CTCAE v4.0 Grade ≥2) regardless of causality.
• Mood disorders as judged by the Investigator or a Psychiatrist, or who meets the cut-off score of ≥12 in the Patient Health Questionnaire (PHQ)-9 or a cut-off score of ≥ 15 in the Generalized Anxiety Disorder (GAD)-7 mood scale, respectively, or selects a positive response of '1, 2, or 3' to question 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of the total score or the PHQ-9)
• anxiety or depression ≥ Grade 3
• 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, or patients with active severe personality disorders (defined according to DSM- IV) are not eligible. Note: for patients with psychotropic treatments ongoing at baseline, the dose and the schedule should not be modified
• Previously untreated brain metastases. Patients who have received radiation or surgery for brain metastases are eligible if there is no evidence of central nervous system (CNS) disease progression, and at least 28 days (4 weeks) have elapsed since treatment. Patients are not permitted to receive enzyme inducing anti-epileptic drugs (EIAEDs) during the study and should not be receiving chronic corticosteroid therapy for CNS metastases.
• Leptomeningeal metastases or spinal cord compression due to disease.
• Acute or chronic liver, renal disease or pancreatitis.
• Uncontrolled diabetes mellitus. Type II diabetics are eligible if they require only oral hypoglycemic agents and fasting blood glucose level is ≤120. Type I diabetics are eligible if HbAlc is \<8.
• Presence of active gastrointestinal (GI) disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea Grade ≥2, and malabsorption syndrome).

Sponsors & Collaborators

• SCRI Development Innovations, LLC: lead
• Novartis: collaborator

Study Sites (3)

Florida Cancer Specialists-South

Fort Myers, Florida, 33916, United States

Location

Nebraska Methodist Hospital

Omaha, Nebraska, 68114, United States

Location

Tennessee Oncology PLLC

Nashville, Tennessee, 37203, United States

Location

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

NVP-BKM120; cabazitaxel

Condition Hierarchy (Ancestors)

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

Study Officials

• John D. Hainsworth, M.D.

  SCRI Development Innovations, LLC

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: January 10, 2014
• First Posted: January 14, 2014
• Study Start: April 1, 2014
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: February 11, 2016

Record last verified: 2016-02

Locations

US (3)