Trial of Dasatinib (Sprycel®) in Subjects With Hormone-refractory Prostate Cancer
Condition: Hormone-refractory Prostate Cancer; Adenocarcinoma of the Prostate; Hormone-resistant Prostate Cancer; Prostate Cancer; Recurrent Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Dasatinib
Intervention description: 150mg (3 pills) orally daily for as long as the drug benefits
Intervention MeSH terms: Dasatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 38.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: prostate

Summary:

      The purpose of this research study is to find out if a new anti-cancer drug, dasatinib
      (Sprycel®), previously approved for treatment of some forms of leukemia, will be safe and
      helpful in treating patients with hormone-refractory prostate cancer.

      This is a research study because the study drug, dasatinib (Sprycel®), has not been evaluated
      for safety or effectiveness in patients with hormone-refractory prostate cancer. The drug is
      approved by the Food and Drug Administration for treatment of some forms of leukemia; thus,
      dasatinib (Sprycel®) is not an investigational drug. It has been given safely to hundreds of
      patients already. However its safety and usefulness in this study population (prostate
      cancer) is unknown.

      Subjects who agree to participate will take 150mg (3 pills) of dasatinib (Sprycel®) daily by
      mouth for as long as the drug benefits them. During this time, the subject will periodically
      return to the office for blood/urine tests, X-rays, imaging scans, and/or to complete
      questionnaires.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Must have biopsy-proven adenocarcinoma of the prostate

          -  Must have hormone-refractory prostate cancer, defined as an increasing PSA by >= 3
             ng/ml from androgen-blockade nadir, or new measurable or evaluable lesion on imaging
             studies, after treatment with orchiectomy, luteinizing hormone-releasing hormone
             (LHRH) agonist, antiandrogen or diethylstilbestrol (DES)

          -  Subjects must have received at least one cycle of single-agent or combination
             chemotherapy for hormone refractory prostate cancer (HRPC), last administered at least
             4 weeks prior to the start of dasatinib

          -  Subjects may not have received more than one type (single agent or combination) of
             chemotherapy regimen; subjects may include (but are not limited to) the following:
             HRPC subjects who were treated with palliative chemotherapy and either failed to
             respond, or responded for a period of time but now have worsening disease (i.e.
             relapsed/refractory to chemotherapy); HRPC subjects who were treated with palliative
             chemotherapy but stopped treatment because of toxicity (i.e. intolerant of
             chemotherapy); HRPC subjects who have been treated with palliative chemotherapy with
             response, whose chemotherapy has been interrupted, and who now have evidence of
             progressive disease (i.e. potentially chemotherapy responsive but subject does not
             desire to restart cytotoxic drugs)

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

          -  Life expectancy of at least 8 weeks, based on clinical judgment of the treating
             physician

          -  Adequate hematologic, renal and liver function as evidenced by the following (subjects
             may have lower hematologic parameters if the cytopenias are thought by the treating
             physician to be secondary to marrow involvement by prostate cancer):

          -  white blood cell count (WBC) > 2.0 bil/L; grade 0-1

          -  absolute neutrophil count (ANC) > 1.0 bil/L; grade 0-1

          -  Platelets > 100 bil/L; grade 0-1

          -  Hemoglobin > 8.0gm/dL

          -  Creatinine < 1.5x upper limit of normal (ULN)

          -  Prothrombin time (PT), Partial Thromboplastin Time (PTT) < 1.2 x ULN; grade 0-1

          -  Total bilirubin < 2x ULN

          -  aspartate aminotransferase (AST), alanine aminotransferase (ALT) < 2.5x ULN

          -  Na, K, Mg, P, Ca >= lower limit of normal

          -  Elevated PSA level (at least 3 ng/mL), or measurable prostate cancer by CT or MRI
             scans (PSA level must have shown two consecutive increases [at >= 14 day intervals]
             since the previous nadir)

          -  Ability to take oral medication (dasatinib must be swallowed whole)

          -  Subjects of reproductive potential must agree to use an adequate method of
             contraception throughout treatment and for at least 4 weeks after study drug is
             stopped

          -  Signed informed consent documents including Health Insurance Portability and
             Accountability Act (HIPAA) according to institutional guidelines

          -  Concomitant Medications: Patient agrees to discontinue St. Johns Wort while receiving
             dasatinib therapy (in addition Patient agrees that IV bisphosphonates will be withheld
             for the first 8 weeks of dasatinib therapy due to risk of hypocalcemia)

        Exclusion Criteria:

          -  Subjects should have had no chemotherapy within 4 weeks of the start of treatment with
             dasatinib

          -  Prior localized radiotherapy for metastatic disease is permitted, provided the
             treatment volume is less than25% of potential marrow space (the radiotherapy must have
             been completed 6 weeks prior to enrollment)

          -  Systemic radiotherapy with samarium-153 must have been completed at least 2 months
             prior to enrollment (subjects may not have received prior strontium-89 [Metastron]
             therapy)

          -  At least 6 weeks have elapsed from the last dose of cytotoxic or targeted therapeutics
             to the time of prescreening; if the subject has received a combination regimen of
             standard chemotherapy plus an investigational agent, a 6 week washout period is
             required

          -  Subjects may not have received treatment with any kinase inhibitor

          -  At least 2 months must have elapsed from time of dosing with vaccines to the time of
             prescreening

          -  No malignancy, other than prostate cancer, that required radiotherapy or systemic
             treatment within the past 5 years

          -  Subjects may not have any of the following: Clinical evidence of uncontrolled heart
             failure, myocardial infarction, or angina within the previous 6 months; prolonged QT
             interval Fridericia's (QTcF) > 450msec; history of unstable ventricular arrhythmias
             (ventricular tachycardia, ventricular fibrillation, or torsades de pointes);
             concomitant use of drugs known to cause torsades de pointes [quinidine, procainamide,
             disopyramide, amiodarone, sotalol, ibutilide, dofetilide, erythromycins,
             clarithromycin, chlorpromazine, haloperidol, mesoridazine,thioridazine, pimozide,
             cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone,
             halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine] (these agents must
             have been discontinued at least 7 days prior to starting dasatinib); subjects with
             hypokalemia or hypomagnesemia are excluded if the electrolyte anomaly cannot be
             corrected

          -  Subjects may not be enrolled with any of the following: History of a significant
             bleeding disorder unrelated to cancer, including diagnosed congenital bleeding
             disorders (e.g., von Willebrand's disease), and diagnosed acquired bleeding disorder
             within one year (e.g., acquired anti-factor VIII antibodies); GI bleeding from any
             cause within 3 months; Concomitant use of anticoagulants, except for low-dose warfarin
             (for prophylaxis to prevent catheter thrombosis) or heparin flushes (for IV lines), is
             prohibited (Note that chronic use of aspirin is prohibited)

          -  Subjects must meet the following restrictions: Subjects may not have a concurrent
             medical condition which may increase the risk of toxicity, including pleural or
             pericardial effusion of any grade, or uncontrolled hypertension; Concomitant use of H2
             blockers or proton pump inhibitors with dasatinib is not recommended (The use of
             antacids should be considered in place of H2 blockers or proton pump inhibitors in
             patients receiving dasatinib therapy); Patient must discontinue St. Johns Wort while
             receiving dasatinib therapy; Subjects must not use intravenous bisphosphonates during
             the first 8 weeks of dasatinib therapy due to risk of hypocalcemia; Subjects may not
             be receiving any restricted cytochrome P450 3A4 (CYP3A4) inhibitors (If the
             investigator feels that any of these agents should be given as uniquely useful for a
             clear diagnosis, the situation should be discussed with the Principal Investigator,
             and a clear monitoring program should be planned)

          -  Subjects may not have evidence of untreated intracranial metastases, or untreated
             prostate cancer producing spinal cord compression