A Safety Study of Abiraterone Acetate Administered in Combination With Docetaxel in Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Cougar Biotechnology, Inc.
ClinicalTrials.gov Identifier:
NCT01400555
First received: July 21, 2011
Last updated: August 11, 2014
Last verified: August 2014
  Purpose

The purpose of this study is to evaluate the maximum safe dose of abiraterone acetate administered in combination with docetaxel plus prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC).


Condition Intervention Phase
Prostate Neoplasms
Prostate Cancer
Drug: Cohort 4
Drug: Cohort 3
Drug: Cohort 2
Drug: Cohort 1
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1b Safety Study of Abiraterone Acetate (JNJ-212082) and Docetaxel in Subjects With Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Resource links provided by NLM:


Further study details as provided by Cougar Biotechnology, Inc.:

Primary Outcome Measures:
  • Proportion of patients with a dose-limiting toxicity [ Time Frame: Up through Week 6 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Proportion of patients with prostate-specific antigen (PSA) response [ Time Frame: Up to Month 36 ] [ Designated as safety issue: No ]
  • Time to PSA progression [ Time Frame: Up to Month 36 ] [ Designated as safety issue: No ]
  • Objective response rate [ Time Frame: Up to Month 36 ] [ Designated as safety issue: No ]
  • Radiographic progression-free survival [ Time Frame: Up to Month 36 ] [ Designated as safety issue: No ]
  • Survival [ Time Frame: Up to Month 36 ] [ Designated as safety issue: No ]

Enrollment: 22
Study Start Date: September 2011
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 001
Cohort 1 Docetaxel 60 mg/m2 administered once every 3 weeks + abiraterone acetate 500 mg/day + prednisone 10 mg/day
Drug: Cohort 1
Docetaxel 60 mg/m2 administered once every 3 weeks + abiraterone acetate 500 mg/day + prednisone 10 mg/day
Experimental: 002
Cohort 2 Docetaxel 75 mg/m2 administered once every 3 weeks + abiraterone acetate 500 mg/day + prednisone 10 mg/day
Drug: Cohort 2
Docetaxel 75 mg/m2 administered once every 3 weeks + abiraterone acetate 500 mg/day + prednisone 10 mg/day
Experimental: 003
Cohort 3 Docetaxel 75 mg/m2 administered once every 3 weeks + abiraterone acetate 1000 mg/day + prednisone 10 mg/day
Drug: Cohort 3
Docetaxel 75 mg/m2 administered once every 3 weeks + abiraterone acetate 1000 mg/day + prednisone 10 mg/day
Experimental: 004
Cohort 4 Docetaxel 75 mg/m2 administered once every 3 weeks + abiraterone acetate 750 mg/day + prednisone 10 mg/day
Drug: Cohort 4
Docetaxel 75 mg/m2 administered once every 3 weeks + abiraterone acetate 750 mg/day + prednisone 10 mg/day

Detailed Description:

This is an open-label (patients and their doctors will know the identity of study drug administered), uncontrolled (patients are not assigned to treatment by chance), multicenter safety study of escalating dose levels of abiraterone acetate administered in combination with docetaxel plus prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC). This study is conducted in 2 parts. Part I consists of Screening, Treatment, assessment of dose-limiting toxicity (DLT), and determination of the maximum tolerated dose (MTD). Participants are enrolled in sequential 6-subject cohorts (groups) and administered combination therapy (abiraterone acetate and docetaxel plus prednisone) according to a dose-escalation schedule. The abiraterone acetate dose in this study will escalate from 500 mg to 1000 mg daily until the MTD is determined. The MTD is the highest combination dose among the dose combinations investigated in this study at which no more than 2 (33%) of the patients in a cohort experience a DLT. A DLT is defined by an adverse event occurring from Day 1 Week 2 (first dose of abiraterone acetate) to the day before the Day 1 Week 7 docetaxel infusion (3 weeks after the second docetaxel infusion); non-hematological toxicity >=Grade 3; Grade 4 neutropenia lasting more than 5 days, neutropenia complicated by fever, or systemic infection; thrombocytopenia <25,000/mcL, or any thrombocytopenia requiring platelet transfusion; and, any subjectively intolerable toxicity. Part II of the study consists of Continuing Treatment, when patients remain at the allocated dose level, escalate to the combination MTD, or discontinuation of docetaxel (if toxicity or intolerability develops) and continue abiraterone acetate (up to 1000 mg/day) plus prednisone, until disease progression; End of Treatment, when posttreatment efficacy and safety will be documented; and Follow-Up, when survival status and new antitumor therapy are monitored. Blood samples for pharmacokinetic and efficacy measurements will be collected at selected times during the study. Safety will be monitored. The total duration of study participation may be up to 36 months. Oral abiraterone acetate will be administered as a single daily dose (500, 750, or 1000 mg). Docetaxel will be administered once every 3 weeks as an intravenous (IV) infusion (60 or 75 mg/m2) over 1 hour. Study participants will premedicate with oral dexamethasone 8 mg 1, 3, and 12 hours before the start of each docetaxel IV infusion. Oral prednisone 5 mg will be administered twice daily.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adenocarcinoma of the prostate
  • Metastatic disease documented by bone, computed tomography (CT), or magnetic resonance image (MRI) scan
  • Surgical or medical castration with testosterone less than 50 ng/dL
  • Prostate cancer progression documented by 1 of the following: PSA progression according to Prostate Cancer Working Group 2 (PCWG2) criteria, radiographic progression by modified Response Evaluation Criteria in Solid Tumors (RECIST) or bone scan
  • Absolute neutrophil count >1,500 cells/mm3
  • Platelets >100,000/µl
  • Hemoglobin >=10.0 g/dL
  • Eastern Cooperative Group (ECOG) status score of <=2.

Exclusion Criteria:

  • Elevated liver function tests (LFTs): Serum bilirubin >upper limit of normal (ULN), alanine (ALT) or aspartate (AST) aminotransferase > 1.5 ULN concomitant with alkaline phosphatase > 2.5 ULN
  • Small cell carcinoma of the prostate
  • Pulmonary or brain metastasis, liver metastasis is allowed if LFTs are not elevated
  • Pre-existing neuropathy or severe fluid retention
  • Prior cytotoxic chemotherapy for metastatic prostate cancer
  • Prior therapy with other CYP17 inhibitor(s) or investigational agent(s) targeting the androgen receptor for metastatic prostate cancer
  • Treatment of primary tumor within 4 weeks of Day 1 Week 1 with surgery, radiation, chemotherapy or immunotherapy
  • Use of investigational drug within 4 weeks of Day 1 Week 1 or current enrollment in an investigational drug or device study
  • Prior ketoconazole for prostate cancer
  • Recent history of ischemic heart disease, electrocardiogram (ECG) abnormalities, or atrial fibrillation.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01400555

Locations
United States, California
Los Angeles, California, United States
United States, New York
New York, New York, United States
United States, Wisconsin
Madison, Wisconsin, United States
Sponsors and Collaborators
Cougar Biotechnology, Inc.
Investigators
Study Director: Cougar Biotechnology, Inc. Clinical Trial Cougar Biotechnology, Inc.
  More Information

No publications provided by Cougar Biotechnology, Inc.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Cougar Biotechnology, Inc.
ClinicalTrials.gov Identifier: NCT01400555     History of Changes
Other Study ID Numbers: CR018712, COU-AA-206
Study First Received: July 21, 2011
Last Updated: August 11, 2014
Health Authority: United States: Food and Drug Administration
United States: Federal Government

Keywords provided by Cougar Biotechnology, Inc.:
Prostate Cancer
Metastatic Castration-Resistant Prostate Cancer
Abiraterone Acetate
Docetaxel
Prednisone
Dexamethasone

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Docetaxel
Prednisone
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal

ClinicalTrials.gov processed this record on October 01, 2014