Phase Ib of Abiraterone Acetate Plus BEZ235 or BKM120 in Castration-resistant Prostate Cancer (CRPC) Patients

Novartis

Status and phase

Completed

Phase 1

Conditions

Castration-resistant Prostate Cancer

Treatments

Drug: BEZ235

Drug: BKM120

Study type

Interventional

Funder types

Industry

Identifiers

NCT01634061

2012-002250-23 (EudraCT Number)

CBEZ235D2101

Details and patient eligibility

About

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.

Full 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.

Enrollment

43 patients

Sex

Male

Ages

18+ years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

43 participants in 4 patient groups

Dose escalation: BEZ235 + Zytiga®

Experimental group

Description:

BEZ235 oral twice daily: 200 mg, 300 mg, and 400 mg dose levels to be tested in the dose escalation part in combination with abiraterone acetate Zytiga® abiraterone acetate oral once daily: 1000 mg taken with low dose prednisone as per the label

Treatment:

Drug: BEZ235

Dose escalation: BKM120 + Zytiga®

Experimental group

Description:

BKM120 oral once daily: 60 mg, 80 mg and 100 mg dose levels to be tested in the dose escalation part in combination with abiraterone acetate Zytiga® abiraterone acetate oral once daily: 1000 mg taken with low dose prednisone as per the label

Treatment:

Drug: BKM120

Dose expansion: BEZ235 + Zytiga®

Experimental group

Description:

Treatment:

Drug: BEZ235

Dose Expansion: BKM120 + Zytiga®

Experimental group

Description:

Treatment:

Drug: BKM120