Prostate Cancer
Conditions
Keywords
Metastatic, castrate-resistant prostate cancer, bone metastasis
Brief 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.
Interventions
DRUGZD4054
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
Sponsors
AstraZeneca
University of Wisconsin, Madison
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Subjects Whose Tumor Lesion Size Changed After 6 Weeks of Treatment With ZD4054 Using PET and MRI Scans. | Week 6 | 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. |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
Countries
United States
Participant flow
Recruitment details
Subjects were screened and enrolled at the University of Wisconsin Carbone Cancer Center from April 2010 until July 2011.
Participants by arm
| Arm | Count |
|---|---|
| ZD4054 ZD4054 + multimodal PET/MRI imaging | 6 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | ZD4054 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 5 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Prior Therapy Prior Antiandrogen and Cytotoxic Chemotherapy | 5 Participants |
| Prior Therapy Prior Antiandrogen Therapy (no prior chemo) | 1 Participants |
| Region of Enrollment United States | 6 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 6 / 6 |
| serious Total, serious adverse events | 4 / 6 |
Outcome results
Primary
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.
Time frame: Week 6
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ZD4054 | The Number of Subjects Whose Tumor Lesion Size Changed After 6 Weeks of Treatment With ZD4054 Using PET and MRI Scans. | 0 participants |
Secondary
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
Time frame: Week 6
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ZD4054 | 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 | 0 participants |
Secondary
Number of Subjects With PSA Response
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ZD4054 | Number of Subjects With PSA Response | 0 participants |
Secondary
The Number of Subjects Whose Tumor Lesion Size Changed Using Diffusion-weighted Imaging (DWI)-Magnetic Resonant Imaging (MRI) Alone
Time frame: Week 6
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ZD4054 | The Number of Subjects Whose Tumor Lesion Size Changed Using Diffusion-weighted Imaging (DWI)-Magnetic Resonant Imaging (MRI) Alone | 0 participants |
Secondary
The Number of Subjects Whose Tumor Lesion Size Changed Using Positron Emission Tomography (PET) Imaging Alone.
Time frame: Week 6
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ZD4054 | The Number of Subjects Whose Tumor Lesion Size Changed Using Positron Emission Tomography (PET) Imaging Alone. | 0 participants |