Clinical trial NCT01634061: Phase Ib of Abiraterone Acetate Plus BEZ235 or BKM120 in Castration-resistant Prostate Cancer (CRPC) Patients
Official title: Phase Ib Dose Finding Study of Abiraterone Acetate Plus BEZ235 or BKM120 in Patients With Castration-resistant Prostate Cancer.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Castration-resistant Prostate Cancer
Keywords: Castration-resistant prostate cancer, abiraterone acetate, BEZ235, BKM120, dose escalation, abiraterone acetate failure
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2012-07-06
Enrollment: 43
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of dose limiting toxicities (DLTs)
timeFrame: from days 1-35 in BEZ235/abiraterone acetate arm and from days 1-28 in BKM120/abiraterone acetate arm
measure: Prostate specific antigen (PSA) decline ≥ 30%
timeFrame: At week 12 or later after treatment discontinuation
Secondary outcomes:
measure: Number of patients with at least one adverse event
timeFrame: Treatment start until 30 days after the last dose
measure: radiological Progression Free Survival as per RECIST 1.1 and PCWG2
timeFrame: Every 12 weeks until disease progression
measure: radiological Response Rate according to RECIST 1.1
timeFrame: Every 12 weeks until disease progression
measure: Overall Survival
timeFrame: From treatment start until 75% of deaths from any cause have occurred
measure: Number and percentage of patients with laboratory abnormalities
timeFrame: Treatment start until 30 days after the last dose
measure: Changes in ECG (electrocardiogram)
timeFrame: Treatment start until 30 days after the last dose
measure: Changes in vital signs
timeFrame: Treatment start until 30 days after the last dose
measure: Changes in mood scales
timeFrame: Treatment start until 30 days after the last dose
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center SC
state: California
city: Hackensack
country: United States
facility: Hackensack University Medical Center Hackensack Univ
state: New Jersey
city: Brussels
country: Belgium
facility: Novartis Investigative Site
city: Wilrijk
country: Belgium
facility: Novartis Investigative Site
city: Vancouver
country: Canada
facility: Novartis Investigative Site
state: British Columbia
city: Marseille
country: France
facility: Novartis Investigative Site
city: Villejuif Cedex
country: France
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Sutton
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: