Phase 2
N=33
Abiraterone Acetate Dose-Escalation Study in Hormone Refractory Prostate Cancer
Prostate Neoplasms
Bottom Line
View on ClinicalTrials.gov: NCT00473746 ↗Enrolled (actual)
33
Serious AEs
19.7%
Results posted
Apr 2014
Primary outcome: Primary: Phase 1: Maximum Tolerated Dose (MTD) of Abiraterone Acetate — NA mg/day
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Abiraterone acetate (Drug); prednisone/prednisolone or dexamethasone (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- Male
- Sponsor
- Janssen Research & Development, LLC
- Primary completion
- Dec 2012
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Phase 1: Maximum Tolerated Dose (MTD) of Abiraterone Acetate |
NA | — |
| PRIMARY Phase 2: Participants With Greater Than or Equal to 50 Percent Decline in Prostate Specific Antigen (PSA) |
26; 2; 28 | — |
| SECONDARY Phase 1: Maximum Plasma Concentration (Cmax) of Abiraterone Acetate |
283.000; 330.633; 289.533; 509.500; 421.000; 676.000 | — |
| SECONDARY Phase 1: Time to Reach the Maximum Plasma Concentration (Tmax) of Abiraterone Acetate |
2.000; 1.500; 2.033; 1.833; 2.044; 2.667 | — |
| SECONDARY Phase 1: Area Under the Plasma-Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) of Abiraterone Acetate |
1329.178; 1625.059; 1565.659; 3039.937; 1310.715; 3624.781 | — |
| SECONDARY Phase 1: Area Under the Plasma-Concentration-time Curve From Time 0 to Infinite Time (AUCINF_obs) of Abiraterone Acetate |
1411.268; 1781.374; 1665.454; 3478.385; 1386.939; 3839.804 | — |
| SECONDARY Phase 1: Terminal Half-life (HL_Lambda_z) of Abiraterone Acetate |
5.284; 10.591; 7.066; 14.361; 5.125; 6.913 | — |
| SECONDARY Phase 1: Total Body Clearance (Cl_F_obs) of Abiraterone Acetate |
4288.456; 5440.949; 1518.748; 2649.954; 529.606; 391.046 | — |
| SECONDARY Phase 1: Volume of Distribution (Vz_F_obs) of Abiraterone Acetate |
653.745; 10252.077; 13688.367; 25494.398; 3940.400; 3418.280 | — |
| SECONDARY Phase 2: Radiographic Progression Free Survival (RAD-PFS) |
NA | — |
| SECONDARY Phase 2: PSA Progression Free Survival (PSA-PFS) |
473 | — |
| SECONDARY Phase 2: Radiographic Objective Response Rate (RAD-ORR) |
9; 1 | — |
| SECONDARY Phase 2: Time to PSA Progression |
497 | — |
| SECONDARY Phase 2: Duration of PSA Response |
477 | — |
| SECONDARY Phase 2: Participants With Change in Eastern Cooperative Oncology Group (ECOG) Performance Status Score |
20; 13; 0; 0; 0; 28 | — |
| SECONDARY Phase 2: Overall Survival |
NA | — |
| SECONDARY Phase 2: Duration of Objective Response |
NA | — |
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).
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 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 =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)
Data sourced from ClinicalTrials.gov (NCT00473746). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.