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

• ClinicalTrials.gov Identifier: NCT01845792
• Recruitment Status: Terminated
• First Posted: May 3, 2013
• Results First Posted: June 4, 2018
• Last Update Posted: June 4, 2018
• Sponsor: University of Colorado, Denver
• Collaborator: Janssen Services, LLC
• Information provided by (Responsible Party): University of Colorado, Denver

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Prostate Cancer	Drug: Cabazitaxel with Abiraterone Acetate; Drug: Cabazitaxel	Phase 2

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 evaluated, so the research team will study the safety and effectiveness of the combination.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 7 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Abiraterone Acetate and Prednisone in Combination With Cabazitaxel, Compared to Cabazitaxel Alone, in Patients With Metastatic Castrate Resistant Prostate Cancer.
• Actual Study Start Date: July 2013
• Actual Primary Completion Date: February 2017
• Actual Study Completion Date: February 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cabazitaxel with Abiraterone Acetate; Cabazitaxel administered as a single intravenous dose every 3 weeks, in combination with abiraterone acetate and prednisone taken daily.	Drug: Cabazitaxel with Abiraterone Acetate; Cabazitaxel intravenously every 3 weeks, in combination with abiraterone acetate and prednisone orally daily.; Other Names: Jevtana; Zytiga
Active Comparator: Cabazitaxel Alone; Cabazitaxel administered as a single intravenous dose every 3 weeks	Drug: Cabazitaxel; Cabazitaxel intravenously every 3 weeks; Other Name: Jevtana

Outcome Measures

Primary Outcome Measures :

1. Progression-Free Survival [ Time Frame: 3 months ]
   Progression-free survival at 3 months.

Secondary Outcome Measures :

1. PSA Response [ Time Frame: 2 years ]
   Prostate specific antigen (PSA) decline by 50% or more from baseline.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 95 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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 acetate, but not within the 3 months prior to study drug dosing.
• Testosterone level <50 ng/mL. Patients receiving Leutinizing Hormone Releasing Hormone (LHRH) agonists or antagonists must be continued to maintain castrate levels of testosterone while on study.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.

• Adequate hematologic function:

  1. platelet >100, 000/uL;
  2. neutrophil count of >1500 cell/mm3;
  3. hemoglobin >9.0 g/dL)
• Adequate renal function (Creatinine clearance > 50 mL/min)
• Adequate potassium level (> 3.5 mEq/dL)

• Adequate hepatic function

  1. bilirubin < 1.5 X upper limit of normal (ULN),
  2. alanine aminotransferase (ALT) < 1.5 X ULN,
  3. aspartate aminotransferase (AST) < 1.5 X ULN.
  4. serum albumin of ≥ 3.0 g/dL.
• Controlled blood pressure, defined as blood pressure ≤ 140/90 on average (3 separate readings taken at screening visit in a relaxed clinical environment and averaged)
• Must be able to take oral medication without crushing, dissolving or chewing tablets

• Willing to take abiraterone acetate on empty stomach;

  (1) 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 this 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, or
• Cytotoxic anti-cancer therapy within 3 weeks, or
• Non-cytotoxic anti-cancer therapy within 2 weeks, or 5 half-lives (whichever is shorter) of Study Day 1.
• Prior radiotherapy to ≥ 40% of bone marrow.
• Prior treatment with Radium 223.
• Use of an investigational therapeutic agent 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 or hypersensitivity 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. (see section 7.2.3 for details)
• Serious infection requiring parenteral antibiotics within 14 days of enrollment.
• Poorly controlled diabetes (Hgb A1C >9).
• Active or symptomatic viral hepatitis or Chronic liver disease, including Child-Pugh Class B and C liver disease.
• History of pituitary or adrenal dysfunction.

• Clinically significant heart disease as evidenced by:

  1. myocardial infarction, or
  2. arterial thrombotic events in the past 6 months,
  3. severe or unstable angina, or
  4. New York Heart Association Class III-IV heart disease, or
  5. 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:

  1. bicalutamide within 6 weeks of study drug dosing, or
  2. flutamide within 4 weeks of study dosing.
• 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

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

  Study Documents (Full-Text)

Documents provided by University of Colorado, Denver:

Study Protocol and Statistical Analysis Plan  [PDF] June 28, 2016

More Information

• Responsible Party: University of Colorado, Denver
• ClinicalTrials.gov Identifier: NCT01845792
• Other Study ID Numbers: 13-1489.cc; NCI-2013-01356 ( Other Identifier: National Cancer Institute )
• First Posted: May 3, 2013
• Results First Posted: June 4, 2018
• Last Update Posted: June 4, 2018
• Last Verified: May 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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; Prostatic Diseases; Abiraterone Acetate; Antineoplastic Agents; Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Cytochrome P-450 Enzyme Inhibitors