Hormone-Resistant Prostate Cancer, Metastatic Malignant Neoplasm in the Bone, Recurrent Prostate Carcinoma, Stage IV Prostate Cancer
Conditions
Brief summary
This phase II trial is studying how well fluorine F 18 sodium fluoride positron emission tomography (PET) works in evaluating response to dasatinib in patients with prostate cancer and bone metastases. Diagnostic procedures, such as fluorine F 18 sodium fluoride PET, may help doctors predict a patient's response to treatment and help plan the best treatment.
Detailed description
PRIMARY OBJECTIVES: I. Determine if changes in regional fluoride incorporation, measured by 18F-fluoride PET (SUV and Ki), occur in both castration-resistant prostate cancer bone metastases and normal bone as a response to treatment with dasatinib. SECONDARY OBJECTIVES: I. Determine if changes in 18F-fluoride transport (K1), an indicator of blood flow, and therefore, an indirect marker of angiogenesis, occur in both castration-resistant prostate cancer bone metastases and normal bone as a response to treatment with dasatinib. OUTLINE: This is a multicenter study. Patients undergo fluorine F 18 sodium fluoride PET scan at baseline and then at 12 weeks after initiation of treatment with dasatinib. PET parameters (SUV, Ki, and Kl) are also analyzed.
Interventions
RADIATIONFluorine F 18 Sodium Fluoride
Undergo fluorine F 18 sodium fluoride PET scan
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Must be able to provide a written informed consent * Men 18 years or older with metastatic castration-resistant prostate cancer enrolling onto the Febbo clinical trial with dasatinib therapy (must meet all inclusion criteria for dasatinib treatment study and comply with requirements of that specific clinical trial) * Histologic confirmation of original prostate cancer diagnosis * Presence of at least one convincing bone metastasis as defined by bone scintigraphy, computed tomography (CT) scan (magnetic resonance imaging \[MRI\] if indicated), or plain X-ray * Must currently have castrate testosterone levels (\< 50 ng/dL) from orchiectomy or maintenance on a luteinizing hormone-releasing hormone (LHRH) agonist or LHRH antagonist
Exclusion criteria
* On the nilutamide-only arm (Arm A of the clinical therapeutic trial) * Note: However, if a patient crosses-over from nilutamide at the time of progression to add dasatinib therapy, he may be eligible for 18F-fluoride PET imaging protocol if he meets all inclusion criteria for this trial * Any condition that would alter the patient's mental status, prohibiting the basic understanding and/or authorization of informed consent * A serious underlying medical condition that would otherwise impair the patient's ability to receive treatment and imaging studies * Expected lifespan of 12 weeks or less * Extremely poor intravenous access, prohibiting the placement of a peripheral IV line for injection of radiotracer * Initiation of bisphosphonate therapy less than 4 weeks from the first PET scan * Radiation treatment to bone less than 4 weeks from first PET scan * Radiopharmaceutical treatment to bone less than 4 weeks from first PET scan * Treatment with granulocyte-macrophage colony stimulating factor (GM-CSF) or granulocyte CSF (G-CSF) within 4 weeks prior to first PET scan * Inability to lie still for the imaging * Weight \> 300 lbs. (due to equipment specifications)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in 18F-fluoride PET (SUV) - Tumor Bone | Baseline and 12 weeks | Investigation of changes between baseline and 12 weeks in regional fluoride incorporation as measured by 18F-fluoride PET in tumor bone as measured by SUVmax |
| Changes in 18F-fluoride PET SUV - Normal Bone | Baseline and 12 weeks | Investigation of changes between baseline and 12 weeks in regional fluoride incorporation as measured by 18F-fluoride PET (SUV) in normal bone as measured by SUVmax |
| Changes in 18F-fluoride Ki - Tumor Bone | Baseline and 12 weeks | Investigation of changes between baseline and 12 weeks in regional fluoride incorporation as measured by 18F-fluoride PET (Ki) in tumor bone. Ki represents the net uptake of fluoride to the bone mineral compartment and reflects the level of osteoblastic activity in bone |
| Changes in 18F-fluoride Ki - Normal Bone | Baseline and 12 weeks | Investigation of changes between baseline and 12 weeks in regional fluoride incorporation as measured by 18F-fluoride PET (Ki) in normal bone. Ki represents the net uptake of fluoride to the bone mineral compartment and reflects the level of osteoblastic activity in bone |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in 18F-fluoride Transport (by Patlak Flux) - Tumor | Baseline and 12 weeks | Investigation of changes in regional fluoride incorporation as measured by 18F-fluoride transport (Patlak flux) in Tumor. This measurement uses the Patlak method for determining the influx constant. |
| Changes in 18F-fluoride Transport (by Patlak Flux) - Normal | Baseline and 12 weeks | Investigation of changes in regional fluoride incorporation as measured by 18F-fluoride transport (Patlak flux) in normal bone. Palak flux is an indicator of blood flow and an indirect marker of angiogenesis. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Overall Participants receiving 100mg PO QD Dasatinib with F18 Sodium Fluoride PET scans at baseline | 18 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Disease progression | 3 |
| Overall Study | Post-Tx scan uninterpretable | 2 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Overall |
|---|---|
| Age, Continuous | 69 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 17 Participants |
| Region of Enrollment United States | 18 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 18 |
| serious Total, serious adverse events | 0 / 18 |
Outcome results
Primary
Changes in 18F-fluoride Ki - Normal Bone
Investigation of changes between baseline and 12 weeks in regional fluoride incorporation as measured by 18F-fluoride PET (Ki) in normal bone. Ki represents the net uptake of fluoride to the bone mineral compartment and reflects the level of osteoblastic activity in bone
Time frame: Baseline and 12 weeks
Population: Analysis population consists of 37 bone locations in 12 participants who were eligible for the study and had interpretable Pre- and Post-Treatment PET scans
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 18F-Fluoride PET | Changes in 18F-fluoride Ki - Normal Bone | 0.0 mL/min/mL | Standard Deviation 0.01 |
p-value: 0.53Generalized Estimating Equation
Comparison: H0: influx(Ki) is the same in normal and tumor bonesp-value: 0.1095Generalized estimating equations
Primary
Changes in 18F-fluoride Ki - Tumor Bone
Investigation of changes between baseline and 12 weeks in regional fluoride incorporation as measured by 18F-fluoride PET (Ki) in tumor bone. Ki represents the net uptake of fluoride to the bone mineral compartment and reflects the level of osteoblastic activity in bone
Time frame: Baseline and 12 weeks
Population: Analysis population consists of 37 Tumor bone locations in 12 participants who were eligible for the study and had interpretable Pre- and Post-Treatment PET scans
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 18F-Fluoride PET | Changes in 18F-fluoride Ki - Tumor Bone | -0.02 mL/min/mL | Standard Deviation 0.07 |
p-value: 0.16Generalized Estimating Equations
Primary
Changes in 18F-fluoride PET SUV - Normal Bone
Investigation of changes between baseline and 12 weeks in regional fluoride incorporation as measured by 18F-fluoride PET (SUV) in normal bone as measured by SUVmax
Time frame: Baseline and 12 weeks
Population: Analysis population consists of 37 normal bone locations in 12 participants who were eligible for the study and had interpretable Pre- and Post-Treatment PET scans
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 18F-Fluoride PET | Changes in 18F-fluoride PET SUV - Normal Bone | 0.31 SUVmax | Standard Deviation 1.17 |
p-value: 0.32Generalized Estimating Equation
Comparison: H0: No difference in uptake b/w normal \& tumor bonesp-value: <0.001Generalized Estimating Equations
Primary
Changes in 18F-fluoride PET (SUV) - Tumor Bone
Investigation of changes between baseline and 12 weeks in regional fluoride incorporation as measured by 18F-fluoride PET in tumor bone as measured by SUVmax
Time frame: Baseline and 12 weeks
Population: Analysis population consists of 37 bone locations in 12 participants who were eligible for the study and had interpretable Pre- and Post-Treatment PET scans
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 18F-Fluoride PET | Changes in 18F-fluoride PET (SUV) - Tumor Bone | -6.67 SUVmax | Standard Deviation 8.98 |
Comparison: This was an exploratory study and no a priori assumptions were employed.p-value: <0.001GEE
Secondary
Changes in 18F-fluoride Transport (by Patlak Flux) - Normal
Investigation of changes in regional fluoride incorporation as measured by 18F-fluoride transport (Patlak flux) in normal bone. Palak flux is an indicator of blood flow and an indirect marker of angiogenesis.
Time frame: Baseline and 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 18F-Fluoride PET | Changes in 18F-fluoride Transport (by Patlak Flux) - Normal | 0.01 mL/min/mL | Standard Deviation 0.01 |
p-value: 0.0033Generalized Estimating Equations
Comparison: H0: Change Patlak Flux from TP1 to TP2 is the same in normal and tumor bonesp-value: 0.067Generalized estimating equations
Comparison: H0: %Change in Patlak Flux between timepoint 1 and 2 is the same for Normal and Tumor bonesp-value: 0.0278Generalized estimating equations
Secondary
Changes in 18F-fluoride Transport (by Patlak Flux) - Tumor
Investigation of changes in regional fluoride incorporation as measured by 18F-fluoride transport (Patlak flux) in Tumor. This measurement uses the Patlak method for determining the influx constant.
Time frame: Baseline and 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 18F-Fluoride PET | Changes in 18F-fluoride Transport (by Patlak Flux) - Tumor | -0.01 mL/min/mL | Standard Deviation 0.06 |
Comparison: the difference in Patlak flux in tumor bone between baseline and 12 weeks, accounting for the fact that each participant could contribute more than one tumor bone.p-value: 0.1945GEE