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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01634061
Other study ID # CBEZ235D2101
Secondary ID 2012-002250-23
Status Completed
Phase Phase 1
First received
Last updated
Start date September 2012
Est. completion date July 2015

Study information

Verified date September 2015
Source Novartis
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 43
Est. completion date July 2015
Est. primary completion date July 2015
Accepts healthy volunteers No
Gender Male
Age group 18 Years and older
Eligibility 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

Study Design


Intervention

Drug:
BEZ235
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
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
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
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.

Locations

Country Name City State
Belgium Novartis Investigative Site Brussels
Belgium Novartis Investigative Site Wilrijk
Canada Novartis Investigative Site Vancouver British Columbia
France Novartis Investigative Site Marseille
France Novartis Investigative Site Villejuif Cedex
Spain Novartis Investigative Site Barcelona Catalunya
Spain Novartis Investigative Site Madrid
United Kingdom Novartis Investigative Site Sutton
United States Hackensack University Medical Center Hackensack Univ Hackensack New Jersey
United States Cedars Sinai Medical Center SC Los Angeles California

Sponsors (1)

Lead Sponsor Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Spain,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 from days 1-35 in BEZ235/abiraterone acetate arm and from days 1-28 in BKM120/abiraterone acetate arm
Primary 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. At week 12 or later after treatment discontinuation
Secondary Number of patients with at least one adverse event Treatment start until 30 days after the last dose
Secondary radiological Progression Free Survival as per RECIST 1.1 and PCWG2 Every 12 weeks until disease progression
Secondary radiological Response Rate according to RECIST 1.1 Every 12 weeks until disease progression
Secondary Overall Survival From treatment start until 75% of deaths from any cause have occurred
Secondary Number and percentage of patients with laboratory abnormalities Treatment start until 30 days after the last dose
Secondary Changes in ECG (electrocardiogram) Treatment start until 30 days after the last dose
Secondary Changes in vital signs Treatment start until 30 days after the last dose
Secondary Changes in mood scales Treatment start until 30 days after the last dose
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