Study of Abiraterone Acetate and Prednisone in Combination With Cabazitaxel in Patients With Prostate Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Janssen Services, LLC
Information provided by (Responsible Party):
University of Colorado, Denver
ClinicalTrials.gov Identifier:
NCT01845792
First received: April 29, 2013
Last updated: May 6, 2014
Last verified: May 2014
  Purpose

Patients are being asked to take place in this research study because they have advanced prostate cancer that has gotten worse after other treatments. If they join this study they will receive a new combination of drugs that are used to treat prostate cancer.


Condition Intervention Phase
Prostate Cancer
Drug: Cabazitaxel with Abiraterone Acetate and Prednisone
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Study of Abiraterone Acetate and Prednisone in Combination With Cabazitaxel in Patients With Metastatic Castrate Resistant Prostate Cancer That is Refractory to Docetaxel

Resource links provided by NLM:


Further study details as provided by University of Colorado, Denver:

Primary Outcome Measures:
  • Safety and efficacy of Cabazitaxel in combination with Abiraterone acetate and Prednisone [ Time Frame: Every 3 weeks for duration of study treatment ] [ Designated as safety issue: Yes ]

    Phase I dose escalation portion:

    To determine the maximum tolerated dose, dose limiting toxicities, safety, and recommended phase 2 dose of cabazitaxel, administered as a single intravenous dose every 3 weeks, in combination with abiraterone acetate and prednisone taken daily, to patients with castrate-resistant prostate cancer.

    Phase II portion:

    To assess the anti-cancer efficacy of the combination in patients with Castrate Resistant Prostate Cancer (CRPC), as determined by a prostatic specific antigen (PSA) decline of 50% or more from baseline during the first 6 cycles (18 weeks), measured every 3 weeks while on study.



Secondary Outcome Measures:
  • Pharmacokinetics [ Time Frame: First 4 weeks of treatment ] [ Designated as safety issue: No ]
    To evaluate the plasma pharmacokinetics of cabazitaxel when administered in combination with daily abiraterone acetate and prednisone.

  • Efficacy [ Time Frame: Every 3 weeks throughout study treatment duration ] [ Designated as safety issue: No ]

    Phase I dose escalation portion:

    • To describe anti-tumor activity and PSA decline by dose cohort

    Phase II portion:

    • To assess the anti-cancer efficacy of the combination in patients with CRPC, as determined by maximum PSA decline at anytime during study treatment, time to PSA and radiographic progression, radiographic objective response, progression-free survival, overall survival



Estimated Enrollment: 72
Study Start Date: July 2013
Estimated Study Completion Date: July 2019
Estimated Primary Completion Date: July 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cabazitaxel with Abiraterone Acetate and Prednisone
Phase I dose escalation: Cabazitaxel administered as a single intravenous dose every 3 weeks, in combination with abiraterone acetate and prednisone taken daily.
Drug: Cabazitaxel with Abiraterone Acetate and Prednisone
Cabazitaxel intravenously every 3 weeks, in combination with abiraterone acetate and prednisone orally daily.
Other Names:
  • Jevtana
  • Zytiga

Detailed Description:

Abiraterone acetate and cabazitaxel have been approved by the United States Food and Drug Administration (FDA) to treat prostate cancer that has spread to other parts of the body such as the lymph nodes or bone. These drugs are approved individually for use when the cancer has become resistant to other treatments, including chemotherapy with docetaxel. The combination of these two drugs has not been approved, so the research team will study the safety and effectiveness of the combination.

Patients are being asked to participate in this study because their tumor has grown or spread during therapy. Patients may benefit from a new combination of drugs to treat it. Abiraterone acetate and prednisone have been shown to prevent the growth of prostate cancer cells by lowering the level of testosterone in the blood. It works in different areas of the body to block the production of this hormone that signals the cancer cells to grow. Cabazitaxel and prednisone prevent cancer cells from growing by blocking certain structures from functioning properly in the cell. These structures help cells divide and therefore grow. By blocking their function, the cell will not be able to divide and will die.

  Eligibility

Ages Eligible for Study:   18 Years to 95 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent has been obtained.
  • Adults over 18 years of age.
  • Histologically or cytologically proven adenocarcinoma of the prostate.
  • Stage IV disease as evidenced by soft tissue, visceral and/or bony metastasis must be Response Evaluation Criteria in Solid Tumors (RECIST) evaluable on CT scan and/or bone scan
  • Progressive disease while receiving hormonal therapy or after surgical castration documented by at least one of the following: (1) Increase in measurable disease per RECIST 1.1. (2) Appearance of new lesions on bone scan consistent with progressive prostate cancer (>2 new lesions on bone scans if this is the only measure of PD) (3) rising PSA defined as 2 sequential increases above a previous lowest reference value. Each value must be obtained at least 1 week apart.
  • PSA at least 2 ng/mL
  • Received prior docetaxel chemotherapy
  • Received prior abiraterone, but not within the 3 months prior to study drug dosing. Prior therapy with abiraterone is not required for enrollment in the phase I study.
  • Testosterone level <50 ng/mL. Patients receiving Leutinizing hormone releasing hormone (LHRH) agonists must be continued to maintain castrate levels of testosterone while on study.
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
  • Adequate hematologic function (platelet >100, 000/uL; neutrophil count of >1500 cell/mm3; hemoglobin >9.0 g/dL)
  • Adequate renal function (Creatinine clearance >60 mL/min)
  • Adequate potassium level > 3.5 mEq/dL
  • Adequate hepatic function (bilirubin < 1.5 X upper limit of normal (ULN), alanine aminotransferase (ALT) < 1.5 X ULN, aspartate aminotransferase (AST) < 1.5 X ULN. Have a serum albumin of ≥ 3.0 g/dL
  • Must be able to take oral medication without crushing, dissolving or chewing tablets
  • Willing to take abiraterone acetate on empty stomach; no food should be consumed at least two hours before and for at least one hour after the dose of abiraterone acetate is taken
  • Patients must be willing and able to adhere to the prohibitions and restrictions specified in the protocol.
  • Written authorization for use and release of health and research study information has been obtained.
  • Patients who have partners of childbearing potential must be willing to use a method of birth control with adequate barrier protection during the study and for 1 week after the last dose of abiraterone acetate.

Exclusion Criteria:

  • Surgery or radiation therapy within 2 weeks. Cytotoxic anti-cancer therapy within 3 weeks. Non-cytotoxic anti-cancer therapy within 2 weeks, or 5 half-lives (whichever is longer) of Study Day 1.
  • Use of an investigational therapeutic within 30 days
  • Have a history of gastrointestinal disorders (medical disorders or extensive surgery) that may interfere with the absorption of the study agents
  • Prior treatment with cabazitaxel
  • Known chronic infection with human immunodeficiency virus (HIV)
  • Known active, or symptomatic, brain metastasis
  • Blood pressure >140/90 on average (3 separate readings taken at screening visit in a relaxed clinical environment and averaged)
  • History of autoimmune disorder requiring daily corticosteroid therapy of greater than prednisone 10mg daily, or its equivalent
  • Baseline peripheral edema > grade 3
  • Pre-existing diarrhea uncontrolled with supportive care; prior hemorrhagic diarrhea due to ulcerative colitis, inflammatory bowel disease or other cause; active, uncontrolled peptic ulcer disease even in the setting of proton-pump inhibitor or Histamine2-blocker use.
  • Pre-existing peripheral neuropathy grade > 2
  • Documented hypersensitivity (CTCAE grade > 2) to any drug containing polysorbate 80
  • Have known allergies, hypersensitivity, or intolerance to abiraterone acetate or prednisone or their excipients
  • Contraindications to steroid use
  • Need for medications that strongly induce or inhibit cytochrome P450 3A4 (CYP3A4) or cytochrome P450 2D6 (CYP2D6) activity
  • Serious infection requiring parenteral antibiotics within 14 days of enrollment
  • Poorly controlled diabetes (HgbA1C >9)
  • Active or symptomatic viral hepatitis or chronic liver disease
  • History of pituitary or adrenal dysfunction
  • Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association Class III-IV heart disease or cardiac ejection fraction measurement of <50% at baseline.
  • Consumption of food or beverages containing grapefruit juice within 7 days of study drug dosing
  • Use of a first-generation anti-androgen such as bicalutamide within 6 weeks of study drug dosing. Use of flutamide within 4 weeks of study dosing with a continued rise in PSA.
  • Have any condition that, in the opinion of the investigator, would compromise the well-being of the subject or the study or prevent the subject from meeting or performing study requirements
  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: NCT01845792

Locations
United States, Colorado
University of Colorado Cancer Center
Aurora, Colorado, United States, 80045
Sponsors and Collaborators
University of Colorado, Denver
Janssen Services, LLC
Investigators
Principal Investigator: Elaine Lam, MD University of Colorado, Denver
  More Information

No publications provided

Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT01845792     History of Changes
Other Study ID Numbers: 13-1489.cc, NCI-2013-01356
Study First Received: April 29, 2013
Last Updated: May 6, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Colorado, Denver:
Metastatic Castrate Resistant Prostate Cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Prednisone
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents

ClinicalTrials.gov processed this record on August 26, 2014