Clinical trial NCT00473746: Abiraterone Acetate Dose-Escalation Study in Hormone Refractory Prostate Cancer
Official title: Phase I/II Open Label Dose Escalation Study of the 17α-Hydroxylase/ C17,20-Lyase Inhibitor, Abiraterone Acetate in Hormone Refractory Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Prostate Neoplasms
Keywords: Prostate neoplasms
Hormone refractory prostate cancer
Abiraterone acetate
CB7630
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2007-05-15
Enrollment: 66
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety, pharmacokinetics, pharmacodynamics, and anti-tumor activities of abiraterone acetate (also referred to as CB7630) in patients with hormone refractory prostate cancer (HRPC).

Detailed description: This is an open-label (identity of assigned study drug will be known) study to evaluate the safety, pharmacokinetics (study of what the body does to a drug), pharmacodynamics (study of what a drug does to the body), and anti-tumor activities of abiraterone acetate (also known as CB7630) in patients with HRPC. The study will be conducted in 2 phases (Phase 1 and Phase 2). In the first part of the study (Phase 1), the maximum tolerated dose (MTD) of abiraterone acetate will be determined for use in the second part of the study (Phase 2) where the number of patients who achieve at least a 50% decrease in prostate specific antigen (PSA) during treatment with abiraterone acetate will be assessed (MTD from Phase 1). Abiraterone acetate will be taken orally (by mouth) in fed and fasted patients once daily. Doses of abiraterone acetate (starting at 250 mg up to a maximum of 2000 mg) will be taken for 28-day treatment periods to determine the MTD. Patients will take MTD of abiraterone acetate for up to twelve 28 day cycles (12 months; patients will be given the option of staying on abiraterone acetate treatment if they are deriving benefit). In Phase 2, prednisone or dexamethasone will be administered concurrently with abiraterone acetate. Serial pharmacokinetic and pharmacodynamic samples will be collected and safety will be monitored throughout the study.

Eligibility criteria: Inclusion Criteria:

Phase 1

* Histologically confirmed adenocarcinoma of the prostate
* No prior therapy with chemotherapy for prostate cancer
* Ongoing gonadal androgen deprivation therapy with luteinizing hormone-releasing hormone (LHRH) analogues or orchiectomy
* Testosterone \<50 ng/dL
* Progressive disease after androgen deprivation
* The presence of objective metastatic disease is NOT required for study eligibility
* Demonstrate disease progression after antiandrogen withdrawal
* Eastern Cooperative Oncology Group (ECOG) performance status score = 0-1
* Laboratory values within protocol-defined parameters
* Systolic blood pressure \<160 mmHg and diastolic blood pressure \<110mmHg documented on at least 3 different days
* Baseline adrenocorticotropic hormone (ACTH) stimulation test demonstrating a peak cortisol \>18 µg/dL
* Agrees to protocol-defined use of effective contraception
* Life expectancy of \>=12 weeks

Phase 2

* Same as Phase 1 criteria with addition of following criteria
* Neoadjuvant or adjuvant chemotherapy is only allowed if the last dose is \>1 year from Cycle 1 Day 1
* Target or non-target abnormalities must be present either on screening bone scan, computed tomography or magnetic resonance imaging
* No prior treatment with ketoconazole for the management of androgen independent prostate cancer

Exclusion Criteria:

Phase 1

* Therapy with other hormonal therapy, including any dose of megestrol acetate (Megace), finasteride (Proscar), dutasteride (Avodart) any herbal product known to decrease prostate specific antigen (PSA) levels (eg, saw palmetto and PC-SPES), or any systemic corticosteroid within 4 weeks prior to first dose of study drug
* Initiation of bisphosphonate therapy within 4 weeks prior to first dose of study drug
* Therapy with supplements or complementary medicines/botanicals within 4 weeks of first dose of study drug, except for any combination of the following: conventional multivitamin supplements, selenium, lycopene, soy supplements
* Prior radiation therapy completed \<4 weeks prior to enrollment
* Prior chemotherapy for hormone refractory prostate cancer
* Any currently active second malignancy, other than non-melanoma skin cancer
* Systolic blood pressure \>=160 mmHg or diastolic blood pressure \>=110 mmHg measured on at least 2 occasions
* NYHA Class III or IV congestive heart failure
* Myocardial infarction within the 6 months prior to the first dose of study drug
* Serious intercurrent infections or nonmalignant medical illnesses that are uncontrolled
* Active psychiatric illnesses/social situations that would limit compliance with protocol requirements
* Active or uncontrolled autoimmune disease that may require corticosteroid therapy during study

Phase 2

* Same as phase 1 with the following addition
* Abnormal electrocardiogram, including any finding which would interfere with assessment of intervals (patients with long QT syndrome, bundle branch blocks or hemiblocks are prohibited)

Primary outcomes:
measure: Phase 1: Maximum Tolerated Dose (MTD) of Abiraterone Acetate
timeFrame: Up to Cycle 12
measure: Phase 2: Participants With Greater Than or Equal to 50 Percent Decline in Prostate Specific Antigen (PSA)
timeFrame: Up to 12 weeks from start of treatment
Secondary outcomes:
measure: Phase 1: Maximum Plasma Concentration (Cmax) of Abiraterone Acetate
timeFrame: At hours 1, 2, 4, 6, 8, 12, 24 and 48 post dose and pre-dose on day 1, day 8, day 15 and day 22 cycle 1, day 1 cycle 2 and day 1 cycle 3.
measure: Phase 1: Time to Reach the Maximum Plasma Concentration (Tmax) of Abiraterone Acetate
timeFrame: At hours 1, 2, 4, 6, 8, 12, 24 and 48 post dose and pre-dose on day 1, day 8, day 15 and day 22 cycle 1, day 1 cycle 2 and day 1 cycle 3
measure: Phase 1: Area Under the Plasma-Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) of Abiraterone Acetate
timeFrame: At hours 1, 2, 4, 6, 8, 12, 24 and 48 post dose and pre-dose on day 1, day 8, day 15 and day 22 cycle 1, day 1 cycle 2 and day 1 cycle 3
measure: Phase 1: Area Under the Plasma-Concentration-time Curve From Time 0 to Infinite Time (AUCINF_obs) of Abiraterone Acetate
timeFrame: At hours 1, 2, 4, 6, 8, 12, 24 and 48 post dose and pre-dose on day 1, day 8, day 15 and day 22 cycle 1, day 1 cycle 2 and day 1 cycle 3
measure: Phase 1: Terminal Half-life (HL_Lambda_z) of Abiraterone Acetate
timeFrame: At hours 1, 2, 4, 6, 8, 12, 24 and 48 post dose and pre-dose on day 1, day 8, day 15 and day 22 cycle 1, day 1 cycle 2 and day 1 cycle 3
measure: Phase 1: Total Body Clearance (Cl_F_obs) of Abiraterone Acetate
timeFrame: At hours 1, 2, 4, 6, 8, 12, 24 and 48 post dose and pre-dose on day 1, day 8, day 15 and day 22 cycle 1, day 1 cycle 2 and day 1 cycle 3
measure: Phase 1: Volume of Distribution (Vz_F_obs) of Abiraterone Acetate
timeFrame: At hours 1, 2, 4, 6, 8, 12, 24 and 48 post dose and pre-dose on day 1, day 8, day 15 and day 22 cycle 1, day 1 cycle 2 and day 1 cycle 3
measure: Phase 2: Radiographic Progression Free Survival (RAD-PFS)
timeFrame: Up to 12 weeks from start of treatment
measure: Phase 2: PSA Progression Free Survival (PSA-PFS)
timeFrame: Up to 12 weeks from start of treatment
measure: Phase 2: Radiographic Objective Response Rate (RAD-ORR)
timeFrame: Up to 12 weeks from start of treatment
measure: Phase 2: Time to PSA Progression
timeFrame: Up to 12 weeks from start of treatment
measure: Phase 2: Duration of PSA Response
timeFrame: Up to 12 weeks from start of treatment
measure: Phase 2: Participants With Change in Eastern Cooperative Oncology Group (ECOG) Performance Status Score
timeFrame: Up to 12 weeks from start of treatment
measure: Phase 2: Overall Survival
timeFrame: Up to Month 60
measure: Phase 2: Duration of Objective Response
timeFrame: Up to 12 weeks from start of treatment
Other outcomes:
Locations:
city: San Francisco
country: United States
state: California
city: Boston
country: United States
state: Massachusetts
city: Houston
country: United States
state: Texas
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Aggarwal R, Harris A, Formaker C, Small EJ, Molina A, Griffin TW, Ryan CJ. Response to subsequent docetaxel in a patient cohort with metastatic castration-resistant prostate cancer after abiraterone acetate treatment. Clin Genitourin Cancer. 2014 Oct;12(5):e167-72. doi: 10.1016/j.clgc.2014.03.010. Epub 2014 Mar 28.