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

NCT ID: NCT01634061

Last Updated: 2020-12-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

43 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-09-30

Study Completion Date

2015-07-31

Brief Summary

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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

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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.

Conditions

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Castration-resistant Prostate Cancer

Keywords

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Castration-resistant prostate cancer, abiraterone acetate, BEZ235, BKM120, dose escalation, abiraterone acetate failure

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Dose escalation: BEZ235 + Zytiga®

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

Group Type EXPERIMENTAL

BEZ235

Intervention Type DRUG

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.

Dose escalation: BKM120 + Zytiga®

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

Group Type EXPERIMENTAL

BKM120

Intervention Type DRUG

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.

Dose expansion: BEZ235 + Zytiga®

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

Group Type EXPERIMENTAL

BEZ235

Intervention Type DRUG

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.

Dose Expansion: BKM120 + Zytiga®

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

Group Type EXPERIMENTAL

BKM120

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

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.

Intervention Type 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.

Intervention Type DRUG

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.

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Cedars Sinai Medical Center SC

Los Angeles, California, United States

Site Status

Hackensack University Medical Center Hackensack Univ

Hackensack, New Jersey, United States

Site Status

Novartis Investigative Site

Brussels, , Belgium

Site Status

Novartis Investigative Site

Wilrijk, , Belgium

Site Status

Novartis Investigative Site

Vancouver, British Columbia, Canada

Site Status

Novartis Investigative Site

Marseille, , France

Site Status

Novartis Investigative Site

Villejuif, , France

Site Status

Novartis Investigative Site

Barcelona, Catalonia, Spain

Site Status

Novartis Investigative Site

Madrid, , Spain

Site Status

Novartis Investigative Site

Sutton, , United Kingdom

Site Status

Countries

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Denmark Germany Italy Switzerland United States Belgium Canada France Spain United Kingdom

Related Links

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https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=15047

Results for CBEZ235D2101 can be found on the Novartis Clinical Trial Results Website

Other Identifiers

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2012-002250-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CBEZ235D2101

Identifier Type: -

Identifier Source: org_study_id