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

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01634061
• Collaborator: (none)
• Enrollment: 43
• Locations: 10
• Arms: 4
• Duration (Months): 33.9
• Patients Per Site: 4.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Castration-resistant Prostate Cancer	Drug: BEZ235; Drug: BKM120; Drug: BEZ235; Drug: BKM120	Phase 1

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

• Study Type: Interventional
• Actual Enrollment: 43 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (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.
• Study Start Date: Sep 1, 2012
• Actual Primary Completion Date: Jul 1, 2015
• Actual Study Completion Date: Jul 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
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.

Outcome Measures

Primary Outcome Measures

1. Incidence of dose limiting toxicities (DLTs) [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

2. Prostate specific antigen (PSA) decline ≥ 30% [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.

Secondary Outcome Measures

1. Number of patients with at least one adverse event [Treatment start until 30 days after the last dose]

2. radiological Progression Free Survival as per RECIST 1.1 and PCWG2 [Every 12 weeks until disease progression]

3. radiological Response Rate according to RECIST 1.1 [Every 12 weeks until disease progression]

4. Overall Survival [From treatment start until 75% of deaths from any cause have occurred]

5. Number and percentage of patients with laboratory abnormalities [Treatment start until 30 days after the last dose]

6. Changes in ECG (electrocardiogram) [Treatment start until 30 days after the last dose]

7. Changes in vital signs [Treatment start until 30 days after the last dose]

8. Changes in mood scales [Treatment start until 30 days after the last dose]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	Cedars Sinai Medical Center SC	Los Angeles	California	United States	90048
2	Hackensack University Medical Center Hackensack Univ	Hackensack	New Jersey	United States	07601
3	Novartis Investigative Site	Brussels		Belgium	BE-B-1200
4	Novartis Investigative Site	Wilrijk		Belgium	2610
5	Novartis Investigative Site	Vancouver	British Columbia	Canada	V5Z 4E6
6	Novartis Investigative Site	Marseille		France	13273
7	Novartis Investigative Site	Villejuif Cedex		France	94805
8	Novartis Investigative Site	Barcelona	Catalunya	Spain	08036
9	Novartis Investigative Site	Madrid		Spain	28041
10	Novartis Investigative Site	Sutton		United Kingdom	SM2 5PT

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

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

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01634061
• Other Study ID Numbers: CBEZ235D2101; 2012-002250-23
• First Posted: Jul 6, 2012
• Last Update Posted: Dec 9, 2020
• Last Verified: Sep 1, 2015

• Keywords provided by Novartis Pharmaceuticals: Castration-resistant prostate cancer, abiraterone acetate, BEZ235, BKM120, dose escalation, abiraterone acetate failure
• Additional relevant MeSH terms: Prostatic Neoplasms; Dactolisib

Study Results

No Results Posted as of Dec 9, 2020