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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
43
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.
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.
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.
Cedars Sinai Medical Center SC
Los Angeles, California, United States
Hackensack University Medical Center Hackensack Univ
Hackensack, New Jersey, United States
Novartis Investigative Site
Brussels, Belgium
Incidence of dose limiting toxicities (DLTs)
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
Time frame: from days 1-35 in BEZ235/abiraterone acetate arm and from days 1-28 in BKM120/abiraterone acetate arm
Prostate specific antigen (PSA) decline ≥ 30%
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.
Time frame: At week 12 or later after treatment discontinuation
Number of patients with at least one adverse event
Time frame: Treatment start until 30 days after the last dose
radiological Progression Free Survival as per RECIST 1.1 and PCWG2
Time frame: Every 12 weeks until disease progression
radiological Response Rate according to RECIST 1.1
Time frame: Every 12 weeks until disease progression
Overall Survival
Time frame: From treatment start until 75% of deaths from any cause have occurred
Number and percentage of patients with laboratory abnormalities
Time frame: Treatment start until 30 days after the last dose
Changes in ECG (electrocardiogram)
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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.
Novartis Investigative Site
Wilrijk, Belgium
Novartis Investigative Site
Vancouver, British Columbia, Canada
Novartis Investigative Site
Marseille, France
Novartis Investigative Site
Villejuif, France
Novartis Investigative Site
Barcelona, Catalonia, Spain
Novartis Investigative Site
Madrid, Spain
Novartis Investigative Site
Sutton, United Kingdom
Time frame: Treatment start until 30 days after the last dose
Changes in vital signs
Time frame: Treatment start until 30 days after the last dose
Changes in mood scales
Time frame: Treatment start until 30 days after the last dose