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

NCT01634061 | Completed Phase 1

• 2 other identifiers: CBEZ235D21012012-002250-23
• Study Type: interventional
• Target: 43
• Locations: 6 countries
• Sites: 10

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.

Conditions

Castration-resistant Prostate Cancer

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (8)

• Number of patients with at least one adverse event

  Treatment start until 30 days after the last dose

• radiological Progression Free Survival as per RECIST 1.1 and PCWG2

  Every 12 weeks until disease progression

• radiological Response Rate according to RECIST 1.1

  Every 12 weeks until disease progression

• Overall Survival

  From treatment start until 75% of deaths from any cause have occurred

• Number and percentage of patients with laboratory abnormalities

  Treatment start until 30 days after the last dose

Study Arms (4)

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

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

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

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

Drug: BKM120

Interventions

BEZ235 DRUG

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.

Dose escalation: BEZ235 + Zytiga®

BKM120 DRUG

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.

Dose escalation: BKM120 + Zytiga®

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (10)

Cedars Sinai Medical Center SC

Los Angeles, California, 90048, United States

Location

Hackensack University Medical Center Hackensack Univ

Hackensack, New Jersey, 07601, United States

Location

Novartis Investigative Site

Brussels, BE-B-1200, Belgium

Location

Novartis Investigative Site

Wilrijk, 2610, Belgium

Location

Novartis Investigative Site

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Novartis Investigative Site

Marseille, 13273, France

Location

Novartis Investigative Site

Villejuif, 94805, France

Location

Novartis Investigative Site

Barcelona, Catalonia, 08036, Spain

Location

Novartis Investigative Site

Madrid, 28041, Spain

Location

Novartis Investigative Site

Sutton, SM2 5PT, United Kingdom

Location

Related Links

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

MeSH Terms

Interventions

dactolisib; NVP-BKM120

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2012
• First Posted: July 6, 2012
• Study Start: September 1, 2012
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: December 9, 2020

Record last verified: 2015-09

Locations

FR (2); ES (2); CA (1); US (2); BE (2); GB (1)