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

Purpose

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.

Condition	Intervention	Phase
Castration-resistant Prostate Cancer	Drug: BEZ235 Drug: BKM120	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase Ib Dose Finding Study of Abiraterone Acetate Plus BEZ235 or BKM120 in Patients With Castration-resistant Prostate Cancer.

Resource links provided by NLM:

MedlinePlus related topics: Cancer Prostate Cancer

Drug Information available for: Abiraterone acetate

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

Incidence of dose limiting toxicities (DLTs) [ Time Frame: from days 8-35 in BEZ235/abiraterone acetate arm and from days 0-28 in BKM120/abiraterone acetate arm ] [ Designated as safety issue: Yes ]
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: Up to week 12 or later after treatment discontinuation ] [ Designated as safety issue: No ]
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 [ Time Frame: Treatment start until 30 days after the last dose ] [ Designated as safety issue: Yes ]
Time to PSA progression as per PCWG2 [ Time Frame: Monthly until treatment discontinuation and afterwards every 12 weeks ] [ Designated as safety issue: No ]
radiological Progression Free Survival as per RECIST 1.1 and PCWG2 [ Time Frame: Every 12 weeks until disease progression ] [ Designated as safety issue: No ]
radiological Response Rate according to RECIST 1.1 [ Time Frame: Every 12 weeks until disease progression ] [ Designated as safety issue: No ]
Overall Survival [ Time Frame: From treatment start until 75% of deaths from any cause have occurred ] [ Designated as safety issue: No ]
Number and percentage of patients with laboratory abnormalities [ Time Frame: Treatment start until 30 days after the last dose ] [ Designated as safety issue: Yes ]
Changes in ECG (electrocardiogram) [ Time Frame: Treatment start until 30 days after the last dose ] [ Designated as safety issue: Yes ]
Changes in vital signs [ Time Frame: Treatment start until 30 days after the last dose ] [ Designated as safety issue: Yes ]
Changes in mood scales [ Time Frame: Treatment start until 30 days after the last dose ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	122
Study Start Date:	September 2012
Estimated Study Completion Date:	April 2015
Estimated Primary Completion Date:	March 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Dose escalation: BEZ235 + Zytiga®	Drug: BEZ235
Experimental: Dose escalation: BKM120 + Zytiga®	Drug: BKM120
Experimental: 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	Drug: BEZ235
Experimental: 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	Drug: BKM120

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

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 castration resistant 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 (i.e. docetaxel)
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, AA or other CYP17 inhibitors (exception of AA), or MDV3100.
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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01634061

Contacts

Contact: Novartis Pharmaceuticals	1-888-669-6682
Contact: Novartis Pharmaceuticals

Show 28 Study Locations

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director:

Novartis Pharmaceuticals

More Information

No publications provided

Responsible Party:	Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:	NCT01634061 History of Changes
Other Study ID Numbers:	CBEZ235D2101, 2012-002250-23
Study First Received:	June 26, 2012
Last Updated:	April 22, 2013
Health Authority:	Belgium: Federal Agency for Medicinal Products and Health Products Denmark: Danish Health and Medicines Authorities France: Agence Nationale de Securite du Medicament et des produits de sante (ANSM) (formal Afssaps) Germany: Federal Institute for Drugs and Medical Devices Italy: National Institute of Health Netherlands: The Central Committee on Research Involving Human Subjects (CCMO) Sweden: Medical Products Agency Spain: Spanish Agency of Medicines United Kingdom: Medicines and Healthcare Products Regulatory Agency Canada: Health Canada Switzerland: Swiss Agency for therapeutic products United States: Food and Drug Administration

Keywords provided by Novartis:

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

Additional relevant MeSH terms:

Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site

Neoplasms
Genital Diseases, Male
Prostatic Diseases

ClinicalTrials.gov processed this record on May 19, 2013