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

Castration-resistant Prostate Cancer Clinical Trial

Official title:

Phase Ib Dose Finding Study of Abiraterone Acetate Plus BEZ235 or BKM120 in Patients With Castration-resistant Prostate Cancer.

Clinical Trial Details — Status: Completed

Administrative data

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

Study information

• Verified date: September 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• 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

Related Conditions & MeSH terms

• Castration-resistant Prostate Cancer
• Prostatic Neoplasms

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

External Links

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