Trial Outcomes & Findings for A Multicenter Phase I/II Trial of Abiraterone Acetate + BEZ235 in Metastatic, Castration-Resistant Prostate Cancer (NCT NCT01717898)

NCT ID: NCT01717898

Last Updated: 2018-03-27

Results Overview

• Recruitment status: TERMINATED
• Study phase: PHASE1/PHASE2
• Target enrollment: 6 participants
• Primary outcome timeframe: Beginning of study up to 15 months
• Results posted on: 2018-03-27

Participant Flow

Participant milestones

Measure	Phase I: BEZ235 200 mg Dose level 1: 200 mg BEZ235 orally (PO) twice a day (BID) Prednisone: 10/mg PO daily Abiraterone acetate: 1000 mg, PO daily	Phase I: BEZ235 300 mg Dose level 2: 300 mg BEZ235 orally (PO) twice a day (BID) Prednisone: 10/mg PO daily. Abiraterone acetate: 1000 mg, PO daily	Phase I: BEZ235 400 mg Dose level 3: 400 mg BEZ235 orally (PO) twice a day (BID) Prednisone: 10/mg po daily. Prednisone can be modified at the investigator's discretion, but should not be discontinued. Abiraterone acetate: 1000 mg, po.	Phase II Phase II: BEZ235 at MTD Prednisone 5 mg twice daily Abiraterone 1,000 mg daily
Overall Study STARTED	6	0	0	0
Overall Study COMPLETED	0	0	0	0
Overall Study NOT COMPLETED	6	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Multicenter Phase I/II Trial of Abiraterone Acetate + BEZ235 in Metastatic, Castration-Resistant Prostate Cancer

Baseline characteristics by cohort

Measure	Abiraterone/Prednisone + BEZ235 n=6 Participants In Phase I, a dose escalation of BEZ235 will be performed using a standard 3 + 3 design to determine the maximum tolerated dose (MTD) of BEZ235 given in combination with continuous fixed doses of Abiraterone Acetate and prednisone. This BEZ235 dose will be used in the phase II portion of the study. BEZ235: BEZ235 - 200 mg, 300 mg, or 400 mg; po, BID. BEZ235 will be supplied in 200 mg, 300 mg, and 400 mg sachets packaged in boxes. Prednisone: 10/mg po daily. Prednisone can be modified at the investigator's discretion, but should not be discontinued. Abiraterone acetate: 1000 mg, po. Abiraterone Acetate is supplied in 250 mg white tablets, four tablets are to be taken with a full glass of water on an empty stomach once daily.
Age, Continuous	71 years n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants
Region of Enrollment United States	6 participants n=5 Participants

PRIMARY outcome

Timeframe: Beginning of study up to 15 months

Population: Study was terminated during Phase I, Dose level 1 due to toxicity.

Outcome measures

Measure	Phase II Phase II: BEZ235 at MTD Prednisone 5 mg twice daily Abiraterone 1,000 mg daily	BEZ235 n=6 Participants Trough concentration of BEZ235 when used in combination with Abiraterone plus Prednisone.	Abiraterone Acetate Trough concentration of Abiraterone acetate when used in combination with BEZ235 plus Prednisone.	Phase I: BEZ235 400 mg Dose level 3: 400 mg BEZ235 orally (PO) twice a day (BID) Prednisone: 10/mg po daily. Prednisone can be modified at the investigator's discretion, but should not be discontinued. Abiraterone acetate: 1000 mg, po.
Number of Reported Dose Limiting Toxicities When Combining BEZ235 With Abiraterone Acetate (Phase I).	0 Participants	3 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: From day 1 of therapy initiation up to 12 weeks

Population: Study was terminated during Phase I, Dose level 1 due to toxicity.

Anti-tumor responses as defined by a decline in PSA of > 50% following 12 weeks of therapy to the combination of Abiraterone Acetate plus BEZ-235 occur in a cohort of patients who have received prior therapy with Abiraterone Acetate therapy

Outcome measures

Measure	Phase II Phase II: BEZ235 at MTD Prednisone 5 mg twice daily Abiraterone 1,000 mg daily	BEZ235 n=6 Participants Trough concentration of BEZ235 when used in combination with Abiraterone plus Prednisone.	Abiraterone Acetate Trough concentration of Abiraterone acetate when used in combination with BEZ235 plus Prednisone.	Phase I: BEZ235 400 mg Dose level 3: 400 mg BEZ235 orally (PO) twice a day (BID) Prednisone: 10/mg po daily. Prednisone can be modified at the investigator's discretion, but should not be discontinued. Abiraterone acetate: 1000 mg, po.
Anti-tumor Responses as Defined by a Decline in PSA of > 50%	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: From day 1 of therapy initiation up to 12 weeks

Population: Study was terminated during Phase I, Dose level 1 due to toxicity.

Response proportion as defined by a decline in PSA of > 50% following 12 weeks of therapy for patients treated with the combination of BEZ235 and Abiraterone Acetate plus Prednisone (Phase II outcome measure).

Study was terminated during Phase I, Dose level 1 due to toxicity, therefore no Phase II data is available.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Beginning of study up to 15 months

Population: Dose could not be determined. Study was terminated during Phase I, Dose level 1 due to toxicity.

Maximum Tolerated Dose (MTD) for BEZ235 + Abiraterone Acetate (to be determined during Phase I). The MTD of BEZ235 will be the dose when given in combination results in less than 33% dose limiting toxicities (DLT).

Outcome measures

Measure	Phase II Phase II: BEZ235 at MTD Prednisone 5 mg twice daily Abiraterone 1,000 mg daily	BEZ235 n=6 Participants Trough concentration of BEZ235 when used in combination with Abiraterone plus Prednisone.	Abiraterone Acetate Trough concentration of Abiraterone acetate when used in combination with BEZ235 plus Prednisone.	Phase I: BEZ235 400 mg Dose level 3: 400 mg BEZ235 orally (PO) twice a day (BID) Prednisone: 10/mg po daily. Prednisone can be modified at the investigator's discretion, but should not be discontinued. Abiraterone acetate: 1000 mg, po.
Maximum Tolerated Dose for BEZ235 + Abiraterone Acetate (Phase I).	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Beginning of study up to 15 months

Population: Concentrations could not be determined. Study was terminated during Phase I, Dose level 1 due to toxicity.

Trough concentrations of BEZ235 and Abiraterone Acetate plus Prednisone when used in combination during Phase I.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Beginning of Phase II up to 15 months

Population: PFS in Phase II could not be determined. Study was terminated during Phase I, Dose level 1 due to toxicity.

Progression Free Survival (PFS) of the combination of BEZ235 plus Abiraterone Acetate/prednisone as determined by Prostate-Specific Antigen Working Group 2 criteria (PSAWG2 ) during Phase II.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Beginning of Phase II up to 15 months

Population: Time to PSA progression could not be determined. Study was terminated during Phase I, Dose level 1 due to toxicity.

Determination of the time to PSA progression in Phase II based on PSAWG2 criteria.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From beginning of Phase II up to 15 months

Population: ORR could not be determined. Study was terminated during Phase I, Dose level 1 due to toxicity.

Proportion of patients achieving an objective response to BEZ235 + Abiraterone Acetate/prednisone according to RECIST criteria.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Beginning of Phase II up to 15 months

Population: No Adverse Events were collected in Phase II. Study was terminated during Phase I, Dose level 1 due to toxicity.

Number of reported Adverse Events in BEZ235 and Abiraterone Acetate plus Prednisone when used in combination (Phase II).

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: post study

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: post study

Outcome measures

Outcome data not reported

Adverse Events

Phase I: Abiraterone/Prednisone + BEZ235 200 mg

Serious events: 3 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Measure	Phase I: Abiraterone/Prednisone + BEZ235 200 mg n=6 participants at risk Study was terminated during Phase I, Dose level 1 due to toxicity.
Respiratory, thoracic and mediastinal disorders Pneumonitis	16.7% 1/6
Gastrointestinal disorders Mucositis	16.7% 1/6
Vascular disorders Hypotension	16.7% 1/6

Other adverse events

Measure	Phase I: Abiraterone/Prednisone + BEZ235 200 mg n=6 participants at risk Study was terminated during Phase I, Dose level 1 due to toxicity.
Blood and lymphatic system disorders Anemia	16.7% 1/6
Gastrointestinal disorders Bloating	33.3% 2/6
Gastrointestinal disorders Diarrhea	66.7% 4/6
Gastrointestinal disorders Dyspepsia	16.7% 1/6
Gastrointestinal disorders Mucositis oral	66.7% 4/6
Gastrointestinal disorders Nausea	50.0% 3/6
Gastrointestinal disorders Vomiting	16.7% 1/6
General disorders Fatigue	50.0% 3/6
General disorders Malaise	16.7% 1/6
Endocrine disorders Creatinine increased	16.7% 1/6
Endocrine disorders Serum amylase increased	16.7% 1/6
General disorders Weight loss	33.3% 2/6
Metabolism and nutrition disorders Anorexia	66.7% 4/6
Metabolism and nutrition disorders Hypocalcemia	16.7% 1/6
Musculoskeletal and connective tissue disorders Bone pain	16.7% 1/6
Respiratory, thoracic and mediastinal disorders Dyspnea	33.3% 2/6
Respiratory, thoracic and mediastinal disorders Pneumonitis	33.3% 2/6
Respiratory, thoracic and mediastinal disorders Sore throat	16.7% 1/6
Skin and subcutaneous tissue disorders Photosensitivity	16.7% 1/6
Skin and subcutaneous tissue disorders Rash acneiform	33.3% 2/6
Skin and subcutaneous tissue disorders Skin hyperpigmentation	16.7% 1/6
Cardiac disorders Hypotension	16.7% 1/6

Additional Information

Charles Ryan, MD

University of California, San Francisco

Phone: 877-827-3222

Email: clinicaltrials@ucsf.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place