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

• Sponsor: University of Wisconsin, Madison (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01119118
• Collaborator: AstraZeneca (Industry)
• Enrollment: 6
• Location: 1
• Arm: 1
• Duration (Months): 19
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: ZD4054	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pharmacodynamic Response Assessment With PET/MRI Imaging in Patients With Metastatic Prostate CAncer to Bone Treated With ZD4054
• Study Start Date: Apr 1, 2010
• Actual Primary Completion Date: Aug 1, 2011
• Actual Study Completion Date: Nov 1, 2011

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. The Number of Subjects Whose Tumor Lesion Size Changed Using Positron Emission Tomography (PET) Imaging Alone. [Week 6]

2. The Number of Subjects Whose Tumor Lesion Size Changed Using Diffusion-weighted Imaging (DWI)-Magnetic Resonant Imaging (MRI) Alone [Week 6]

3. 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]

4. Number of Subjects With PSA Response [6 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin	United States	53792

Sponsors and Collaborators

• University of Wisconsin, Madison
• AstraZeneca

Investigators

• Principal Investigator: Glenn Liu, M.D., University of Wisconsin, Madison

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• University of Wisconsin Carbone Cancer Center

Publications

None provided.

• Responsible Party: University of Wisconsin, Madison
• ClinicalTrials.gov Identifier: NCT01119118
• Other Study ID Numbers: CO09805; NCI-2011-00736; A534260; SMPH/MEDICINE/MEDICINE*H; H-2009-0160
• First Posted: May 7, 2010
• Last Update Posted: Nov 21, 2019
• Last Verified: Mar 1, 2013

• Keywords provided by University of Wisconsin, Madison: Metastatic; castrate-resistant prostate cancer; bone metastasis
• Additional relevant MeSH terms: Prostatic Neoplasms

Study Results

Participant Flow

Recruitment Details	Subjects were screened and enrolled at the University of Wisconsin Carbone Cancer Center from April 2010 until July 2011.

Arm/Group Title	ZD4054
Arm/Group Description	ZD4054 therapy at the starting dose of 10 mg PO with multimodal PET/MRI imaging
Period Title: Overall Study
STARTED	6
COMPLETED	5
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	ZD4054
Arm/Group Description	ZD4054 + multimodal PET/MRI imaging
Overall Participants	6
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	1 16.7%
>=65 years	5 83.3%
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	6 100%
Region of Enrollment (participants) [Number]
United States	6 100%
Prior Therapy (Number) [Number]
Prior Antiandrogen and Cytotoxic Chemotherapy	5 83.3%
Prior Antiandrogen Therapy (no prior chemo)	1 16.7%

Outcome Measures

1. Primary Outcome

Title	The Number of Subjects Whose Tumor Lesion Size Changed After 6 Weeks of Treatment With ZD4054 Using PET and MRI Scans.
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ZD4054
Arm/Group Description	ZD4054 therapy at the starting dose of 10 mg PO with multimodal PET/MRI imaging
Measure Participants	6
Number [participants]	0 0%

2. Secondary Outcome

Title	The Number of Subjects Whose Tumor Lesion Size Changed Using Positron Emission Tomography (PET) Imaging Alone.
Time Frame	Week 6

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ZD4054
Arm/Group Description	ZD4054 therapy at the starting dose of 10 mg PO with multimodal PET/MRI imaging
Measure Participants	6
Number [participants]	0 0%

3. Secondary Outcome

Title	The Number of Subjects Whose Tumor Lesion Size Changed Using Diffusion-weighted Imaging (DWI)-Magnetic Resonant Imaging (MRI) Alone
Time Frame	Week 6

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ZD4054
Arm/Group Description	ZD4054 therapy at the starting dose of 10 mg PO with multimodal PET/MRI imaging
Measure Participants	6
Number [participants]	0 0%

4. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ZD4054
Arm/Group Description	ZD4054 therapy at the starting dose of 10 mg PO with multimodal PET/MRI imaging
Measure Participants	6
Number [participants]	0 0%

5. Secondary Outcome

Title	Number of Subjects With PSA Response
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ZD4054
Arm/Group Description	ZD4054 therapy at the starting dose of 10 mg PO with multimodal PET/MRI imaging
Measure Participants	6
Number [participants]	0 0%

Adverse Events

Time Frame	14 months
Arm/Group Title	ZD4054
Arm/Group Description	ZD4054 + multimodal PET/MRI imaging
All Cause Mortality
	ZD4054
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	ZD4054
	Affected / at Risk (%)	# Events
Total	4/6 (66.7%)
Cardiac disorders
Supraventricular and nodal arrhythmia - Atrial fibrillation	1/6 (16.7%)	1
Gastrointestinal disorders
Anorexia	1/6 (16.7%)	1
Dehydration	1/6 (16.7%)	1
Diarrhea	2/6 (33.3%)	2
Distension/bloating, abdominal	1/6 (16.7%)	1
Nausea	1/6 (16.7%)	1
General disorders
Fatigue (asthenia, lethargy, malaise)	1/6 (16.7%)	1
Other (Not Including Serious) Adverse Events
	ZD4054
	Affected / at Risk (%)	# Events
Total	6/6 (100%)
Blood and lymphatic system disorders
Lymphopenia	1/6 (16.7%)	1
Cardiac disorders
Cardiac Arrhythmia	2/6 (33.3%)	2
Gastrointestinal disorders
Diarrhea	3/6 (50%)	3
Distension/bloating, abdominal	2/6 (33.3%)	2
Dry mouth/salivary gland (xerostomia)	1/6 (16.7%)	1
Gastritis	1/6 (16.7%)	1
Gastrointestinal - Other	1/6 (16.7%)	1
Nausea	3/6 (50%)	3
Taste alteration (dysgeusia)	1/6 (16.7%)	1
Vomiting	1/6 (16.7%)	1
Hemorrhage, GI - Upper GI NOS	1/6 (16.7%)	1
General disorders
Fatigue (asthenia, lethargy, malaise)	2/6 (33.3%)	2
Fever	3/6 (50%)	3
Edema: limb	1/6 (16.7%)	1
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils - Bronchus	1/6 (16.7%)	1
Investigations
Weight loss	1/6 (16.7%)	1
AST increased	1/6 (16.7%)	1
Albumin, serum-low	1/6 (16.7%)	1
Calcium, serum-low (hypocalcemia)	1/6 (16.7%)	1
Sodium, serum-low (hyponatremia)	2/6 (33.3%)	2
Metabolism and nutrition disorders
Anorexia	3/6 (50%)	3
Musculoskeletal and connective tissue disorders
Muscle weakness	1/6 (16.7%)	1
Musculoskeletal/Soft Tissue - Other	1/6 (16.7%)	1
Pain - Back	1/6 (16.7%)	1
Pain - Bone	2/6 (33.3%)	4
Pain - Extremity-limb	1/6 (16.7%)	1
Pain - Head/headache	2/6 (33.3%)	2
Pain - Joint	1/6 (16.7%)	1
Psychiatric disorders
Insomnia	1/6 (16.7%)	1
Mood alteration - Depression	1/6 (16.7%)	1
Neurology - Other	1/6 (16.7%)	1
Reproductive system and breast disorders
Gynecomastia	1/6 (16.7%)	1
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)	2/6 (33.3%)	2
Cough	1/6 (16.7%)	1
Hypoxia	1/6 (16.7%)	1
Pulmonary/Upper Respiratory - Other	1/6 (16.7%)	1
Vascular disorders
Hematoma	1/6 (16.7%)	1
Hemorrhage/Bleeding - Other	1/6 (16.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.