NaF Positron Emission Tomography/Computed Tomography (PET/CT)Imaging to Assess Treatment Responsiveness to TAK-700 in Patients With Castrate Resistant Prostate Cancer (CRPC) With Bone Metastasis

Study Overview
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Brief Summary
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The purpose of this study is to assess whether NaF PET/CT scans can be used to evaluate treatment response in bone metastases in subjects with prostate cancer treated with the investigational drug, TAK-700.

Official Title
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A Pharmacodynamic Study Using NaF PET/CT Imaging to Assess Treatment Responsiveness to TAK-700 in Patients With Metastatic Castrate Resistant Prostate Cancer to Bone

Conditions
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Prostatic Neoplasms, Prostate Cancer

Intervention / Treatment
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* Drug: TAK-700
* Radiation: Fluorine F 18 Sodium Fluoride
* Procedure: Positron Emission Tomography
* Procedure: Computed Tomography


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male patients 18 years or older Voluntary written consent Histologically proven adenocarcinoma of the prostate Evidence of radiographic bone metastases May have received prior chemotherapy for metastatic disease, but prior chemotherapy is not a requirement for eligibility Eastern Cooperative Oncology Group performance status 0-2 Serum testosterone level is less than or equal to 50 ng/dL Has undergone orchiectomy or plan to continue receiving gonadotropin releasing hormone (GnRH) analogue therapy Adequate organ function as measured by screening laboratory values specified in the protocol Must agree to use appropriate contraceptives prior to study procedures, during duration of study participation and for 4 months after last dose of TAK 700 Must be able to lie flat for greater than or equal to 30 minutes during PET/CT imaging Screening calculated ejection fraction of greater than or equal to 50% by multigated radionuclide angiography (MUGA) scan or Echocardiogram Exclusion Criteria: Received Strontium-89, Samarium-153, or other radioisotope within 3 months of registration history of allergic reactions attributed to compounds similar to sodium fluoride F-18 (NaF) history of seizure disorder Known history of brain metastases Concurrent treatment with any herbal products within 7 days of study entry Received radiotherapy less than or equal to 4 weeks prior to registration Known hypersensitivity to TAK-700 or related compounds Prior therapy for treatment of metastatic castrate resistant prostate cancer with any androgen biosynthesis inhibitor or androgen signaling pathway inhibitor such as: enzalutamide (MDV-3100), abiraterone, ketoconazole, or aminoglutethimide Current bladder neck outlet obstruction Current spinal cord compression Current bilateral hydronephrosis History of adrenal insufficiency History of myocardial infarction, unstable symptomatic ischemic heart disease, ongoing arrhythmias (over grade 2), thromboembolic events, or any other cardiac condition within 6 months prior to first dose of study drug. Uncontrolled high blood pressure Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C Major surgery less than or equal to 4 weeks before the first dose of study drug Serious infection less than or equal to 2 weeks before the first dose of study drug Known gastrointestinal (GI) disease or GI procedure that could interfere with oral absorption or tolerance of TAK-700, including difficulty swallowing capsules

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: TAK-700<br>TAK-700 will be administered at 300 mg orally (PO)twice daily (BID) continuously on 28-day treatment cycles. The most common way of assessing bone metastasis is planar bone scintigraphy or single photon emission computed tomography (SPECT), though both lack high spatial resolution and thus make small metastases detection inaccurate. Positron emission tomography (PET) is a successful imaging modality with a higher resolution than SPECT, but has not been widely adopted in bone imaging. One of the most promising PET imaging agents for detection of bone metastasis is 18F-Sodium Fluoride (Fluorine F 18 Sodium Fluoride, or NaF). NaF uptake is characterized by high and rapid bone uptake accompanied by very rapid blood clearance, which results in a high bone-to-background ration in a short time. | Drug: TAK-700<br>* TAK-700 will be administered at 300mg twice per day on 28-day continuous cycles<br>* Other names: orteronel;Radiation: Fluorine F 18 Sodium Fluoride<br>* Undergo NaF F18 PET/CT scan<br>* Other names: F-18 NaF;Procedure: Positron Emission Tomography<br>* Undergo 18F NaF PET/CT scan<br>* Other names: PET;Procedure: Computed Tomography<br>* Undergo 18F NaF PET/CT scan<br>* Other names: CAT Scan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Change in Maximum NaF PET/CT Standardized Uptake Values | To measure changes in NaF PET/CT standardized uptake values (SUVmax) from prior to dosing with Tak-700 to12 weeks after starting treatment with TAK-700. Value at three months minus value at baseline. | Baseline and 3 months | 
| Number of Participants With Change in Prostate Specific Antigen (PSA) Response Rate | Measure prostate specific antigen (PSA) response rate in patients treated with TAK700, as measured by a decline in the PSA level from baseline to the month 3 assessment according to the Prostate Cancer Clinical Trials Working Group (PCWG2), at least a 50% decrease from baseline. Percent increase or decrease from month three compared to baseline. | Baseline and 3 months | 
| Number of Participants With a Change in Total NaF PET/CT Standardized Uptake Values | To measure changes in NaF PET/CT standardized uptake values (SUV total) from prior to dosing with Tak-700 to12 weeks after starting treatment with TAK-700. Percent change from three months to baseline; value at three months minus value at baseline. | Baseline and 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Who Experience Adverse Events While on Treatment With TAK 700 | The number of subjects experiencing adverse events per CTCAE 4.0 while on treatment. | Up to 12 months | 
| Number of Patients With a Measurable Change in PSA Kinetics With TAK700 From Baseline to Off Treatment | Stable: no change in PSA kinetics Decrease: less than baseline Increase: greater than baseline PSA data was gathered at baseline and off treatment. | Up to 14 months | 
| Number of Participants With Changes in NaF PET/CT Results in Response to TAK700 | This is an exploratory endpoint as we are planning to identify other new parameters during the PET/CT scanning that may be more predictive of response (such as SUV volume, or dynamic changes during the scanning period). Changes in results at week 12 compared to baseline. Value at 12 weeks minus value at baseline. | At baseline and 12 weeks | 
| Compare Changes on NaF PET/CT After Treatment With TAK700 With Standard Clinical Outcomes Including PSA Doubling Time, Response Evaluation Criteria in Solid Tumors (RECIST), and Radiographic Progression Free Survival. |  | Approximately 24 months | 
| Number of Participants With a Change in the Number of Circulating Tumor Cells Using One or More Methods (Epispot) | Baseline compared to 12 weeks. Value at three months minus value at baseline. | At baseline and 12 weeks | 
| Number of Participants With Change in the Number of Circulating Tumor Cells Using the Cell Search System (Veridex, LLC) Obtained Prior to Beginning Treatment With TAK 700, After Completing One Cycle and After Completing 3 Cycles | Change from baseline to one month and three month. | At baseline, one month, three months | 
| PSA Response Rate and Circulating Tumor Cell Counts of Subjects Receiving TAK700 to NaF PET/CT Imaging Results |  | Baseline, one month, 2 months, 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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prostate, prostate cancer