Castration-resistant Prostate CancerPhase 1NCT01634061
Phase Ib of Abiraterone Acetate Plus BEZ235 or BKM120 in Castration-resistant Prostate Cancer (CRPC) Patients
A Phase 1 study testing BEZ235 and BKM120 in people with Castration-resistant Prostate Cancer, run by Novartis Pharmaceuticals at 10 sites in 6 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Castration-resistant Prostate Cancer
- What is being tested?
- BEZ235 and BKM120
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 10 sitesin 6 countries
- Study dates
- Sep 2012to Jul 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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 locations and contacts
10 sites in 6 countries.
10 sites in 6 countries
United States2 sites
Hackensack University Medical Center Hackensack Univ
Hackensack, New Jersey, 07601
Cedars Sinai Medical Center SC
Los Angeles, California, 90048
Belgium2 sites
Novartis Investigative Site
Brussels, BE-B-1200
Novartis Investigative Site
Wilrijk, 2610
France2 sites
Novartis Investigative Site
Marseille, 13273
Novartis Investigative Site
Villejuif, 94805
Spain2 sites
Novartis Investigative Site
Barcelona, Catalonia, 08036
Novartis Investigative Site
Madrid, 28041
About this study
Official title: Phase Ib Dose Finding Study of Abiraterone Acetate Plus BEZ235 or BKM120 in Patients With Castration-resistant Prostate Cancer.
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.
Read the 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.
- Conditions
- Castration-resistant Prostate Cancer
- Being tested
- BEZ235, BKM120
- Keywords
- Castration-resistant prostate cancer, abiraterone acetate, BEZ235, BKM120, dose escalation, abiraterone acetate failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BEZ235Drug
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.
BKM120Drug
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.
BEZ235Drug
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.
BKM120Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| Dose escalation: BEZ235 + Zytiga® | Experimental | 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 Receives: Drug: BEZ235 |
| Dose escalation: BKM120 + Zytiga® | Experimental | 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 Receives: Drug: BKM120 |
| Dose expansion: BEZ235 + Zytiga® | Experimental | 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 Receives: Drug: BEZ235 |
| Dose Expansion: BKM120 + Zytiga® | Experimental | 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 Receives: Drug: BKM120 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: from days 1-35 in BEZ235/abiraterone acetate arm and from days 1-28 in BKM120/abiraterone acetate arm
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.
Measured: At week 12 or later after treatment discontinuation
Secondary outcomes (8)
Number of patients with at least one adverse event
Measured: Treatment start until 30 days after the last dose
radiological Progression Free Survival as per RECIST 1.1 and PCWG2
Measured: Every 12 weeks until disease progression
radiological Response Rate according to RECIST 1.1
Measured: Every 12 weeks until disease progression
Overall Survival
Measured: From treatment start until 75% of deaths from any cause have occurred
Number and percentage of patients with laboratory abnormalities
Measured: Treatment start until 30 days after the last dose
Changes in ECG (electrocardiogram)
Measured: Treatment start until 30 days after the last dose
Changes in vital signs
Measured: Treatment start until 30 days after the last dose
Changes in mood scales
Measured: Treatment start until 30 days after the last dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jul 2012 (estimated)
- Study startSep 2012
- Primary completionJul 2015
- Study completionJul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Castration-resistant Prostate CancerStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01634061
- Sponsor's protocol ID
- CBEZ235D2101
- Other IDs
- 2012-002250-23
- Status last verified
- Sep 2015
- First submitted
- 26 Jun 2012
- Last updated
- 9 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Ib Dose Finding Study of Abiraterone Acetate Plus BEZ235 or BKM120 in Patients With Castration-resistant Prostate Cancer.
- ClinicalTrials.gov ID
- NCT01634061
- Acronym / sponsor ID
- CBEZ235D2101
- Conditions
- Castration-resistant Prostate Cancer
- Keywords
- Castration-resistant prostate cancer, abiraterone acetate, BEZ235, BKM120, dose escalation, abiraterone acetate failure
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Sep 2012
- Primary completion
- Jul 2015 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 6 Jul 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Dose escalation: BEZ235 + Zytiga® | Experimental | Drug: BEZ235BEZ235 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 |
| Dose escalation: BKM120 + Zytiga® | Experimental | Drug: BKM120BKM120 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 |
| Dose expansion: BEZ235 + Zytiga® | Experimental | Drug: BEZ235BEZ235 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 |
| Dose Expansion: BKM120 + Zytiga® | Experimental | Drug: BKM120BKM120 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BEZ235BEZ235 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. | Drug | Dose escalation: BEZ235 + Zytiga® |
| BKM120BKM120 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. | Drug | Dose escalation: BKM120 + Zytiga® |
| BEZ235BEZ235 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. | Drug | Dose expansion: BEZ235 + Zytiga® |
| BKM120BKM120 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. | Drug | Dose Expansion: BKM120 + Zytiga® |
Primary outcome
Incidence of dose limiting toxicities (DLTs)
Time frame: from days 1-35 in BEZ235/abiraterone acetate arm and from days 1-28 in BKM120/abiraterone acetate arm
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%
Time frame: At week 12 or later after treatment discontinuation
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.
8 secondary outcomes
Number of patients with at least one adverse event
Time frame: Treatment start until 30 days after the last dose
radiological Progression Free Survival as per RECIST 1.1 and PCWG2
Time frame: Every 12 weeks until disease progression
radiological Response Rate according to RECIST 1.1
Time frame: Every 12 weeks until disease progression
Overall Survival
Time frame: From treatment start until 75% of deaths from any cause have occurred
Number and percentage of patients with laboratory abnormalities
Time frame: Treatment start until 30 days after the last dose
Changes in ECG (electrocardiogram)
Time frame: Treatment start until 30 days after the last dose
Changes in vital signs
Time frame: Treatment start until 30 days after the last dose
Changes in mood scales
Time frame: Treatment start until 30 days after the last dose
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Dec 2020.
- Results for CBEZ235D2101 can be found on the Novartis Clinical Trial Results WebsiteLink provided by the sponsor.
Related trials for Castration-resistant Prostate Cancer
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RecruitingPhase 2
A Study to Test Inavolisib Treatment in Participants With Metastatic Castration-Resistant Prostate Cancer
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RecruitingPhase 1/2
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Active, not recruitingPhase 2
FPI-2265 (225Ac-PSMA-I&T) and Olaparib for Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC)
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
10 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BEZ235 and BKM120 in people with Castration-resistant Prostate Cancer, run by Novartis Pharmaceuticals at 10 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States, Belgium, France, Spain, Canada and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of dose limiting toxicities (DLTs) (time frame: from days 1-35 in BEZ235/abiraterone acetate arm and from days 1-28 in BKM120/abiraterone acetate arm). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Dec 2020.