ZD4054 With Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) for Prostate Cancer
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: ZD4054
Intervention description: All patients will be treated with ZD4054 at 10 mg PO daily, repeated in four week cycles (1 cycle = 28 days). All patients will initially undergo NaF and FDG PET/CT and MRI imaging at baseline (scan#1), and then again after 4 weeks (scan#2) of ZD4054 exposure. Subsequently, ZD4054 will be held for 2 weeks followed by the final NaF and FDG-PET/CT and MRI acquisition (scan#3). After the final PET/MRI is obtained, patients will resume ZD4054 and be assessed for safety prior to each new cycle of therapy. Standard disease evaluation assessments will be conducted after cycle#3, and repeated after every third cycle (sooner if clinically indicated). Therapy will continue until radiographical/clinical disease progression or unacceptable toxicity
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Metastatic; castrate-resistant prostate cancer; bone metastasis

Summary:

      The purpose of this research study is to assess the effects of ZD4054 on prostate cancer that
      has spread to the bones by using new imaging techniques. In particular, this study will use
      fluorodeoxyglucose (FDG) and 18F-Sodium Fluoride (NaF) PET/computed tomography (CT) and MRI
      scans to look for changes in bone metastasis after ZD4054 therapy.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Men > 18 years of age.

          2. Histologically proven adenocarcinoma of the prostate.

          3. Presence of radiographic bone metastasis with at least one which is amenable to serial
             imaging using MRI/PET imaging.

          4. Patients must have evidence of progressive disease by either radiographic progression
             or a rising PSA within 4 weeks prior to registration.

          5. Patients must have had prior treatment with bilateral orchiectomy or other primary
             androgen-deprivation therapy.

          6. For patients previously treated with flutamide (Eulexin), Nilutamide (Nilandron), or
             bicalutamide (Casodex): Patients must have discontinued flutamide > 4 weeks prior to
             registration with continued evidence of progressive disease. For bicalutamide or
             nilutamide, patients must have discontinued the drug > 6 weeks prior to registration
             with evidence of progressive disease.

          7. Prior therapy is permitted as long as it was given > 4 weeks prior to registration,
             and evidence for disease progression is met.

          8. Patients must not have had prior radiotherapy < 4 weeks prior to registration.

          9. Prior use of bisphosphonates allowed only if started at least 12 or more weeks prior
             to registration (can continue current dose/schedule while on study).

         10. Patient cannot have had prior Strontium 89, Samarium 153, or other radioisotope.

         11. No concurrent use of estrogen, or estrogen-like agents

         12. Patients must have adequate organ function

         13. ECOG performance status 0-2.

        Exclusion Criteria:

          1. Use of potent CYP450 inducers (such as phenytoin, rifampicin, carbamazepine and
             phenobarbitone, St. John's Wort) within 2 weeks prior to start of study treatment.

          2. Prior therapy with endothelin receptor antagonists or family history of
             hypersensitivity to endothelin antagonists.

          3. History of past or current epilepsy, epilepsy syndrome, or other seizure disorder.

          4. Stage II, III or IV cardiac failure (classified according to New York Heart
             Association (NYHA) classification), myocardial infarction within 6 months prior to
             study entry, or have left ventricular function (LVEF) below the institutional normal
             limit.

          5. QT interval corrected for heart rate (by Bazett's correction) (QTcB) >470 msec.

          6. Previous history or presence of another cancer, other than prostate cancer or treated
             squamous/basal cell carcinoma of the skin, within the last 5 years.

          7. Major surgery within 6 weeks of registration.

          8. Hemoglobin (Hb) <9 g/dL. Concomitant use of erythropoietin or blood transfusions is
             allowed.

          9. Inability to take or absorb oral medications.