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

Primary Purpose

Castration-resistant Prostate Cancer

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
BEZ235
BKM120
BEZ235
BKM120
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Castration-resistant Prostate Cancer focused on measuring Castration-resistant prostate cancer, abiraterone acetate, BEZ235, BKM120, dose escalation, abiraterone acetate failure

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept 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

Sites / Locations

  • Cedars Sinai Medical Center SC
  • Hackensack University Medical Center Hackensack Univ
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Dose escalation: BEZ235 + Zytiga®

Dose escalation: BKM120 + Zytiga®

Dose expansion: BEZ235 + Zytiga®

Dose Expansion: BKM120 + Zytiga®

Arm 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

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

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

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

Outcomes

Primary Outcome Measures

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
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.

Secondary Outcome Measures

Number of patients with at least one adverse event
radiological Progression Free Survival as per RECIST 1.1 and PCWG2
radiological Response Rate according to RECIST 1.1
Overall Survival
Number and percentage of patients with laboratory abnormalities
Changes in ECG (electrocardiogram)
Changes in vital signs
Changes in mood scales

Full Information

First Posted
June 26, 2012
Last Updated
December 6, 2020
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT01634061
Brief Title
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

2. Study Status

Record Verification Date
September 2015
Overall Recruitment Status
Completed
Study Start Date
September 2012 (undefined)
Primary Completion Date
July 2015 (Actual)
Study Completion Date
July 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Castration-resistant Prostate Cancer
Keywords
Castration-resistant prostate cancer, abiraterone acetate, BEZ235, BKM120, dose escalation, abiraterone acetate failure

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
43 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Dose escalation: BEZ235 + Zytiga®
Arm Type
Experimental
Arm 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
Arm Title
Dose escalation: BKM120 + Zytiga®
Arm Type
Experimental
Arm 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
Arm Title
Dose expansion: BEZ235 + Zytiga®
Arm Type
Experimental
Arm 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
Arm Title
Dose Expansion: BKM120 + Zytiga®
Arm Type
Experimental
Arm 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
Intervention Type
Drug
Intervention Name(s)
BEZ235
Intervention Description
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
Intervention Name(s)
BKM120
Intervention Description
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
Intervention Name(s)
BEZ235
Intervention Description
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
Intervention Name(s)
BKM120
Intervention Description
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.
Primary Outcome Measure Information:
Title
Incidence of dose limiting toxicities (DLTs)
Description
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
Title
Prostate specific antigen (PSA) decline ≥ 30%
Description
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
Secondary Outcome Measure Information:
Title
Number of patients with at least one adverse event
Time Frame
Treatment start until 30 days after the last dose
Title
radiological Progression Free Survival as per RECIST 1.1 and PCWG2
Time Frame
Every 12 weeks until disease progression
Title
radiological Response Rate according to RECIST 1.1
Time Frame
Every 12 weeks until disease progression
Title
Overall Survival
Time Frame
From treatment start until 75% of deaths from any cause have occurred
Title
Number and percentage of patients with laboratory abnormalities
Time Frame
Treatment start until 30 days after the last dose
Title
Changes in ECG (electrocardiogram)
Time Frame
Treatment start until 30 days after the last dose
Title
Changes in vital signs
Time Frame
Treatment start until 30 days after the last dose
Title
Changes in mood scales
Time Frame
Treatment start until 30 days after the last dose

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Cedars Sinai Medical Center SC
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
Hackensack University Medical Center Hackensack Univ
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Novartis Investigative Site
City
Brussels
ZIP/Postal Code
BE-B-1200
Country
Belgium
Facility Name
Novartis Investigative Site
City
Wilrijk
ZIP/Postal Code
2610
Country
Belgium
Facility Name
Novartis Investigative Site
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 4E6
Country
Canada
Facility Name
Novartis Investigative Site
City
Marseille
ZIP/Postal Code
13273
Country
France
Facility Name
Novartis Investigative Site
City
Villejuif Cedex
ZIP/Postal Code
94805
Country
France
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08036
Country
Spain
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Novartis Investigative Site
City
Sutton
ZIP/Postal Code
SM2 5PT
Country
United Kingdom

12. IPD Sharing Statement

Links:
URL
https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=15047
Description
Results for CBEZ235D2101 can be found on the Novartis Clinical Trial Results Website

Learn more about this trial

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

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