Castration-resistant Prostate Cancer
Conditions
Keywords
Castration-resistant prostate cancer, abiraterone acetate, BEZ235, BKM120, dose escalation, abiraterone acetate failure
Brief summary
This is an open label study of abiraterone acetate in combination with BEZ235 and abiraterone acetate in combination with BKM120 in CRPC patients with abiraterone acetate failure.
Detailed description
A dose-escalation part will first determine the maximum tolerated dose (MTD) and/or recomended dose for expansion (RDE) of abiraterone acetate in combination with BEZ235 and abiraterone acetate in combination with BKM120 in CRPC patients with abiraterone acetate failure. Subsequently, the MTD and/or RDE of each combination will be investigated in two expansion treatment groups of CRPC patients who have failed abiraterone acetate therapy.
Interventions
DRUGBKM120
BKM120 will be supplied as 10mg and 50mg hard gelatin capsules. At each patient's visit, patient will reecive a prescription of an adequate drug supply for self administration at home.
DRUGBEZ235
BEZ235 will be supplied as 50mg, 100mg, 200mg, 300mg and 400mg SDS sachets. At each patient's visit, patient will reecive a prescription of an adequate drug supply for self administration at home.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult males ≥ 18 years old * Eastern Cooperative Oncology Group Performance Status ≤ 2 * Patient must have a castrate level of testosterone (\<= 50 ng/dL or 1.7 nmol/L). ( Castrate status must be maintained by continued GnRH analogues unless patient has undergone surgical orchiectomy). * Histologically or cytologically confirmed diagnosis of advanced or metastatic prostate cancer. * Advanced or metastatic castration-resistant prostate cancer progression after abiraterone acetate failure * Patients should have no more than 2 lines of prior chemotherapies including cytotoxic agents * Discontinuation of all anti-androgen, anti-neoplastic or investigational treatment \>= 4 weeks (6 weeks for bicalutamide).
Exclusion criteria
* Previous treatment with PI3K pathway inhibitors (e.g. PI3K, AKT, mTOR inhibitor), ketoconazole, CYP17 inhibitors (exception of AA), or enzalutamide. * Patient has active uncontrolled or symptomatic CNS metastases * Inadequately controlled hypertension (e.g. systolic blood pressure \>=160 mmHg or diastolic blood pressure \>=95 mmHg) * Patient has a QTcF \> 480 msec on the screening ECG (using the QTcF formula), has a short/long QT syndrome, or history of QT prolongation/Torsades de Pointes * Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drugs * Patient has a 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 (e.g. risk of doing harm to self or others) * Patients who experienced dose reductions and/or treatment interruptions due to abiraterone acetate related toxicities (i.e. serious AEs, AEs, liver toxicities during abiraterone acetate treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of dose limiting toxicities (DLTs) | from days 1-35 in BEZ235/abiraterone acetate arm and from days 1-28 in BKM120/abiraterone acetate arm | Dose escalation part: Determine MTD and /or RDE of the combinations abiraterone acetate + BEZ235 and abiraterone acetate + BKM120 by assessing the incidence of DLTs in cycle 1 |
| Prostate specific antigen (PSA) decline ≥ 30% | At week 12 or later after treatment discontinuation | Dose expansion part: Assess anti-tumor activity of the combinations (abiraterone acetate + BEZ235 and abiraterone acetate + BKM120) in castration-resistant prostate cancer patients with abiraterone acetate failure as on treatment PSA progression according to prostate cancer working group criteria 2 (PCWG2) by assessing PSA decline ≥ 30% at Week 12 or later. |
Secondary
| Measure | Time frame |
|---|---|
| radiological Response Rate according to RECIST 1.1 | Every 12 weeks until disease progression |
| Overall Survival | From treatment start until 75% of deaths from any cause have occurred |
| Number and percentage of patients with laboratory abnormalities | Treatment start until 30 days after the last dose |
| Number of patients with at least one adverse event | Treatment start until 30 days after the last dose |
| Changes in vital signs | Treatment start until 30 days after the last dose |
| Changes in mood scales | Treatment start until 30 days after the last dose |
| Changes in ECG (electrocardiogram) | Treatment start until 30 days after the last dose |
| radiological Progression Free Survival as per RECIST 1.1 and PCWG2 | Every 12 weeks until disease progression |
Countries
Belgium, Canada, France, Spain, United Kingdom, United States
Outcome results
None listed