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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01634061
First received: June 26, 2012
Last updated: February 24, 2014
Last verified: February 2014
  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:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • 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 ] [ 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: At 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 ]
  • 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: October 2015
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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
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.
Experimental: 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
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.
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
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.
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
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.

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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

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

  Show 37 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals 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: February 24, 2014
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 August 28, 2014