ZD4054 With Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) for Prostate Cancer

Study Overview
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Brief Summary
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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.

Official Title
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Pharmacodynamic Response Assessment With PET/MRI Imaging in Patients With Metastatic Prostate CAncer to Bone Treated With ZD4054

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: ZD4054


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men > 18 years of age. Histologically proven adenocarcinoma of the prostate. Presence of radiographic bone metastasis with at least one which is amenable to serial imaging using MRI/PET imaging. Patients must have evidence of progressive disease by either radiographic progression or a rising PSA within 4 weeks prior to registration. Patients must have had prior treatment with bilateral orchiectomy or other primary androgen-deprivation therapy. 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. Prior therapy is permitted as long as it was given > 4 weeks prior to registration, and evidence for disease progression is met. Patients must not have had prior radiotherapy < 4 weeks prior to registration. 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). Patient cannot have had prior Strontium 89, Samarium 153, or other radioisotope. No concurrent use of estrogen, or estrogen-like agents Patients must have adequate organ function ECOG performance status 0-2. Exclusion Criteria: 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. Prior therapy with endothelin receptor antagonists or family history of hypersensitivity to endothelin antagonists. History of past or current epilepsy, epilepsy syndrome, or other seizure disorder. 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. QT interval corrected for heart rate (by Bazett's correction) (QTcB) >470 msec. 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. Major surgery within 6 weeks of registration. Hemoglobin (Hb) <9 g/dL. Concomitant use of erythropoietin or blood transfusions is allowed. Inability to take or absorb oral medications.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>ZD4054 + multimodal PET/MRI imaging | Drug: ZD4054<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Subjects Whose Tumor Lesion Size Changed After 6 Weeks of Treatment With ZD4054 Using PET and MRI Scans. | Multimodal Positron Emission Tomography (PET) and Magnetic Resonant Imaging (MRI) imaging were used to evaluate changes in the tumor lesion size following 6 weeks of treatment with ZD4054. | Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Subjects Whose Tumor Lesion Size Changed Using Positron Emission Tomography (PET) Imaging Alone. |  | Week 6 | 
| The Number of Subjects Whose Tumor Lesion Size Changed Using Diffusion-weighted Imaging (DWI)-Magnetic Resonant Imaging (MRI) Alone |  | Week 6 | 
| Number of Subjects Whose Tumor Lesion Size Changed Using Iterative Decomposition of Water and Fat With Echo Asymmetry and Least-squares Estimation (IDEAL)-MRI Imaging Alone |  | Week 6 | 
| Number of Subjects With PSA Response |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic, castrate-resistant prostate cancer, bone metastasis