Trial record 1 of 2 for:    Dasatinib and Abiraterone and Prostate
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Abiraterone Acetate and Prednisone With or Without Dasatinib in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by University of Southern California
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Southern California
ClinicalTrials.gov Identifier:
NCT01685125
First received: September 11, 2012
Last updated: January 27, 2014
Last verified: January 2014
  Purpose

This phase II trial studies how well giving abiraterone acetate and prednisone with or without dasatinib works in treating patients with metastatic, hormone-resistant prostate cancer. Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as abiraterone acetate, may lessen the amount of androgens made by the body. Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether abiraterone acetate and prednisone is more effective than abiraterone acetate, prednisone, and dasatinib in treating prostate cancer


Condition Intervention Phase
Hormone-resistant Prostate Cancer
Recurrent Prostate Cancer
Stage IV Prostate Cancer
Drug: abiraterone acetate
Drug: dasatinib
Drug: prednisone
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase II Trial of Dasatinib Plus Abiraterone Compared to Abiraterone Alone for Metastatic, Castration-Resistant Prostate Cancer Prior to Chemotherapy

Resource links provided by NLM:


Further study details as provided by University of Southern California:

Primary Outcome Measures:
  • Progression-free survival (PFS) [ Time Frame: From the start of abiraterone acetate until first evidence of disease progression or until death from any cause, whichever occurs first, assessed up to 3 years ] [ Designated as safety issue: No ]
    PFS defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. A one-sided, 0.05-level log rank test will be used to compare the two arms in terms of PFS. PFS will be estimated using the product-limit method of Kaplan and Meier.


Secondary Outcome Measures:
  • Overall response [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Overall response defined as the percent of subjects whose best response is a complete response or partial response based on RECIST version 1.1. Exact 95% confidence intervals will be calculated for this estimate.

  • PSA change response according to PSA Working Group Criteria 2 [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
    PSA changes will be summarized for each arm also using waterfall plots as well as standard descriptive statistics.

  • Overall survival [ Time Frame: From start of abiraterone acetate and/or dasatinib treatment until death due to any cause or time the patient was last known to be alive, assessed up to 3 years ] [ Designated as safety issue: No ]
    Estimated using the product-limit method of Kaplan and Meier. The probability of remaining alive at 6, 12, 18 and 24 months, with the associated Greenwood's standard errors, will be summarized.

  • Intent-to-treat analysis [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 96
Study Start Date: September 2012
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm A (abiraterone acetate, prednisone)
Abiraterone acetate 1000 mg PO QD and Prednisone 5 mg PO BID on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Drug: abiraterone acetate
Given PO
Other Names:
  • CB7630
  • Zytiga
Drug: prednisone
Given PO
Other Names:
  • DeCortin
  • Deltra
Experimental: Arm B (abiraterone acetate, prednisone, dasatinib)
Abiraterone acetate 1000 mg PO QD, Prednisone 5 mg PO BID, and dasatinib 100 mg PO QD on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Drug: abiraterone acetate
Given PO
Other Names:
  • CB7630
  • Zytiga
Drug: dasatinib
Given PO
Other Names:
  • BMS-354825
  • Sprycel
Drug: prednisone
Given PO
Other Names:
  • DeCortin
  • Deltra

Detailed Description:

PRIMARY OBJECTIVES:

I. To compare the progression-free survival of men with metastatic castration-resistant prostate cancer treated with abiraterone (abiraterone acetate) plus dasatinib to that of men treated with abiraterone alone.

SECONDARY OBJECTIVES:

I. To describe the toxicity profile of the combination, as well as the rate of prostate-specific antigen (PSA) response, objective responses, and changes in circulating tumor cell (CTC) numbers.

OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM A: Patients receive abiraterone acetate 1000 mg orally (PO) once daily (QD) and prednisone 5 mg PO twice daily (BID) on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive abiraterone acetate and prednisone as patients in arm A. Patients also receive dasatinib 100 mg PO QD on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

  Eligibility

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

Inclusion Criteria:

  • Metastatic, castration-resistant prostate cancer

    • Defined as evaluable radiographic disease with rising PSA x 2 (at least 1 week apart) or radiographic progression (new soft tissue/bone lesions or enlarging soft tissue lesions) despite medical or surgical castration
    • No limit on prior hormonal therapies (i.e. anti-androgens, ketoconazole) except that subject must not have received abiraterone previously
    • No limit on prior biologic therapies (i.e. immune therapy, antiangiogenic, targeted) except that patient should not have received dasatinib or other v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) (src)-targeted therapy
  • No prior chemotherapy for metastatic disease

    * Subjects who have received chemotherapy in the neoadjuvant or adjuvant setting will be eligible provided chemotherapy was completed > 6 months prior to enrollment

  • Eastern Cooperative Oncology Group (ECOG) 0-2
  • Total bilirubin =< 1.5 times the institutional upper limit of normal (ULN) except for Gilbert's syndrome
  • Hepatic enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT] ) =< 2.5 times the institutional ULN
  • Serum sodium (Na), potassium (K+), magnesium (Mg+), phosphate and calcium (Ca+) > lower limit of normal (LLN)
  • Serum creatinine =< 1.5 time the institutional ULN
  • Hemoglobin (Hb) >= 9
  • Platelets >= 100,000
  • Absolute neutrophil count (ANC) >= 1000
  • Ability to take oral medication (study medications must be swallowed whole)
  • Men with fathering potential must agree to use contraception throughout study treatment; acceptable methods include: condoms, sponge, intrauterine device (IUD), oral contraceptives
  • Concomitant medications * Patient agrees to discontinue St. Johns wort while receiving dasatinib therapy (discontinue St. Johns wort at least 5 days before starting dasatinib)

Exclusion Criteria:

  • Known hepatitis B or C or human immunodeficiency virus (HIV), regardless of viral load

    * Testing for the purposes of enrollment is not mandatory, however a documented history of these infections will be exclusionary due to concerns for drug-drug interactions with antivirals and potential for increased risk of liver toxicity

  • Radiation for palliation of bony metastases within the preceding 2 weeks
  • Prior chemotherapy for metastatic castration-resistant prostate cancer (CRPC)

    * Immune therapy with sipuleucel-T is allowed, provided the last infusion was >= 28 days prior to study therapy and there has been at least one documented PSA value rising after completion of sipuleucel-T therapy or progression of disease on imaging after sipuleucel-T

  • Malignancy (aside from prostate cancer) which required radiotherapy or systemic treatment within the past 5 years

    • Superficial bladder cancer treated with intravesical therapy and currently in remission will not be an exclusion
    • Skin cancers will not be an exclusion, except for melanoma with a thickness > 1 mm
  • Concurrent medical condition which may increase the risk of toxicity, including:

    • Pleural or pericardial effusion of any grade at the time of study entry
    • Cardiac symptoms; any of the following should be considered for exclusion: ** Uncontrolled angina, congestive heart failure or myocardial infarction (MI) within (6 months)

      • Diagnosed congenital long QT syndrome
      • Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes) ** Prolonged QTc/f interval on pre-entry electrocardiogram (> 450 msec)
      • Subjects with hypokalemia or hypomagnesemia if it cannot be corrected prior to abiraterone administration
  • History of significant bleeding disorder unrelated to cancer, including:

    • Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease)
    • Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies)
    • Ongoing or recent (=< 3 months) significant gastrointestinal bleeding
  • Prohibited treatments and/or therapies

    • Subjects should not be on any additional anti-cancer therapy except for luteinizing hormone-releasing hormone (LHRH) agonist/antagonist; specifically excluded medications include ketoconazole, estrogens, and anti-androgens
    • Category I drugs that are generally accepted to have a risk of causing Torsades de pointes including: (Patients must discontinue drug 7 days prior to starting dasatinib)

      • Quinidine, procainamide, disopyramide
      • Amiodarone, sotalol, ibutilide, dofetilide
      • Erythromycin, clarithromycin
      • Chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide
      • Cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine
  • Prisoners or subjects who are involuntarily incarcerated
  • Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness
  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: NCT01685125

Locations
United States, California
USC Norris Comprehensive Cancer Center Recruiting
Los Angeles, California, United States, 90033
Contact: Kristy Massopust    323-865-0843    Kristy.Massopust@med.usc.edu   
Principal Investigator: Tanya B. Dorff         
Sponsors and Collaborators
University of Southern California
Investigators
Principal Investigator: Tanya Dorff University of Southern California
  More Information

No publications provided

Responsible Party: University of Southern California
ClinicalTrials.gov Identifier: NCT01685125     History of Changes
Other Study ID Numbers: 4P-12-1, NCI-2012-01485
Study First Received: September 11, 2012
Last Updated: January 27, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Prostatic Neoplasms
Prostatic Diseases
Dasatinib
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
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
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014