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

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

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.

Study Overview

• Status: Terminated
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: ZD4054

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Carbone Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 1; ZD4054 + multimodal PET/MRI imaging

Drug: ZD4054; 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

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Collaborators: AstraZeneca
• Investigators: Principal Investigator: Glenn Liu, M.D., University of Wisconsin, Madison

Publications and helpful links

General Publications

• Simoncic U, Perlman S, Liu G, Staab MJ, Straus JE, Jeraj R. Comparison of NaF and FDG PET/CT for assessment of treatment response in castration-resistant prostate cancers with osseous metastases. Clin Genitourin Cancer. 2015 Feb;13(1):e7-e17. doi: 10.1016/j.clgc.2014.07.001. Epub 2014 Jul 15.

Helpful Links

• University of Wisconsin Carbone Cancer Center

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): August 1, 2011
• Study Completion (Actual): November 1, 2011

Study Registration Dates

• First Submitted: May 5, 2010
• First Submitted That Met QC Criteria: May 6, 2010
• First Posted (Estimate): May 7, 2010

Study Record Updates

• Last Update Posted (Actual): November 21, 2019
• Last Update Submitted That Met QC Criteria: November 13, 2019
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Keywords: Metastatic; bone metastasis; castrate-resistant prostate cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: CO09805; A534260 (Other Identifier: UW Madison); SMPH/MEDICINE/MEDICINE*H (Other Identifier: UW Madison); NCI-2011-00736 (Registry Identifier: NCI Trial ID); H-2009-0160 (Other Identifier: Institutional Review Board)