Bone Metastases, Castrate-resistant Prostate Cancer, Recurrent Prostate Cancer, Stage IV Prostate Cancer
Conditions
Keywords
castrate resistant prostate cancer, CRPC, cabozantinib, XL184
Brief summary
This study is being done to help researchers understand more about prostate cancer that has spread to the bones by using the newest magnetic resonance imaging (MRI) techniques and to better understand the effect of an experimental drug called XL184 (or cabozantinib) on bone disease. The other purposes of the study are to better understand the effect of XL184 on prostate cancer progression, bone pain, and on any cancer cells that patients may have circulating within the blood (called circulating tumor cells)
Detailed description
PRIMARY OBJECTIVES: I. To determine effect of XL184 on the functional MRI metrics Ktrans and apparent diffusion coefficient (ADC) within castrate resistant prostate cancer bone metastases. SECONDARY OBJECTIVES: I. To quantify progression free survival in men with castrate resistant prostate cancer (CRPC) treated with XL184 according to Prostate Cancer Working Group criteria. II. To correlate and changes in MRI based functional metrics with bone scan, prostate specific antigen (PSA), Response Evaluation Criteria in Solid Tumors (RECIST) response criteria, circulating tumor cells (CTC) number and with changes in pain. III. To explore c-MET, phospho-c-MET staining on circulating tumor cells as a predictive biomarker for response and duration of response to XL-184. OUTLINE: Patients receive cabozantinib orally (PO) once daily (QD). Treatment continues in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically.
Interventions
DRUGcabozantinib
Given PO
OTHERlaboratory biomarker analysis
Correlative studies
PROCEDUREmagnetic resonance imaging
Undergo MRI
Sponsors
Endeavor Health
University of Chicago
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
MALE
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed prostate cancer with progressive disease * Evidence of castration resistance defined as disease progression despite a testosterone level \< 50ng/dL (or surgical castration) * Evidence of metastatic disease to the bones within the lumbar spine, sacrum, or pelvic bones that is identifiable on screening pelvic MRI * If patient has had prior pelvis radiation therapy (RT), then bone metastases must be out of radiated port (e.g. lumbar or sacral spine) * Any prior therapy for castrate disease acceptable other than prior XL184 with a minimum washout of 28 days for any other anticancer therapy * Patients with castrate resistant disease post antiandrogen therapy/withdrawal must meet at least one of the following criteria: * Have not received docetaxel chemotherapy * Have received docetaxel chemotherapy but received less then 225mg/m2 cumulative dose * Have documented liver metastases * Have no pain or pain that does not require a long acting (SR) narcotic * Have received mitoxantrone chemotherapy in the past for CRPC
Exclusion criteria
* Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study * Patients who are receiving any other investigational agents * Prior treatment with other vascular endothelial growth factor (VEGF) or c-MET targeted therapies * History of hematemesis or hemoptysis * The subject has uncontrolled or significant intercurrent illness * The patient requires concomitant treatment, in therapeutic doses, with anticoagulants
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Functional MRI Metrics Ktrans Between 2 Weeks and Baseline | baseline, 2 weeks | Ktrans is a measurement calculating the volume transfer constant of the contrast reagent and essentially is a measurement of vascular perfusion. To determine the effect of XL184 on the functional MRI metrics Ktrans, Ktrans parameters were measured at baseline, two week time-point, 12 weeks, and 24 weeks for disease monitoring. Change between baseline and 2 weeks reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Bone Scan Response | baseline, 2 weeks | Bone Scan Response at weeks 2, 12, and 24 were collected. Change between baseline and 2 weeks are reported Bone Scan Response were measured as increase, decrease, or stable of bone lesions and scored as 1, -1, or 0, respectively, where higher values represent a worse outcome. |
| Correlation of Percent Change in the Functional MRI Metrics to RECIST Tumor Measurements | baseline, 12 weeks, and 24 weeks | The protocol proposed to collect RECIST tumor measurements at weeks 0, 12, and 24. However, the data were not collected |
| Association of Progression Free Survival (PFS) With Ktrans and ADC | From start of treatment to time of progression or death, whichever occurs first, assessed up to 1 year | Time to progression or progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. The approximate survival after standard therapies in this setting is bleak and in the order of months. Too few events for a meaningful statistical analysis; no significant results were obtained in Cox regression analyses. Therefore, we calculated the median PFS time and its 95% confidence interval. |
| Correlation of Percent Change in the Functional MRI Metrics With CTC | baseline, 12 weeks, and 24 weeks | The protocol proposed to collect CTC measurements at weeks 0, 12, and 24. However, the data were not collected |
| Change in Pain Scale Between 12 Weeks and Baseline | baseline,12 weeks | Pain scores are measured at baseline and weeks 12, and 24. Change between baseline and 12 weeks are reported . In the pain score ranged from 0 to 10. 10 denotes most pain. |
| Change of PSA Between 12 Weeks and Baseline | baseline, 12 weeks | PSA at weeks 0, 12, and 24 were collected. Change between baseline and 12 weeks are reported |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Enzyme Inhibitor Therapy) Patients receive cabozantinib PO QD. Treatment continues in the absence of disease progression or unacceptable toxicity.
cabozantinib: Given PO
laboratory biomarker analysis: Correlative studies
magnetic resonance imaging: Undergo MRI | 17 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
Baseline characteristics
| Characteristic | Treatment (Enzyme Inhibitor Therapy) |
|---|---|
| Age, Continuous | 68 years |
| 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 | 16 Participants |
| Region of Enrollment United States | 17 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 17 |
| other Total, other adverse events | 15 / 17 |
| serious Total, serious adverse events | 4 / 17 |
Outcome results
Primary
Change in the Functional MRI Metrics Ktrans Between 2 Weeks and Baseline
Ktrans is a measurement calculating the volume transfer constant of the contrast reagent and essentially is a measurement of vascular perfusion. To determine the effect of XL184 on the functional MRI metrics Ktrans, Ktrans parameters were measured at baseline, two week time-point, 12 weeks, and 24 weeks for disease monitoring. Change between baseline and 2 weeks reported.
Time frame: baseline, 2 weeks
Population: 2 individuals had missing values for Ktrans from baseline to 24 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Treatment (Enzyme Inhibitor Therapy) | Change in the Functional MRI Metrics Ktrans Between 2 Weeks and Baseline | 0.026 per minute (or min-1) | Standard Deviation 0.005 |
Comparison: The least square means of ktrans at different time points (baseline, 2 weeks, 12 weeks, 24 weeks) are estimated by a linear mixed model. Comparison of means at different time points were performed. The primary result reported below is for the difference of means between 2 weeks and baseline.p-value: 0.0016Mixed Models Analysis
Secondary
Association of Progression Free Survival (PFS) With Ktrans and ADC
Time to progression or progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. The approximate survival after standard therapies in this setting is bleak and in the order of months. Too few events for a meaningful statistical analysis; no significant results were obtained in Cox regression analyses. Therefore, we calculated the median PFS time and its 95% confidence interval.
Time frame: From start of treatment to time of progression or death, whichever occurs first, assessed up to 1 year
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Enzyme Inhibitor Therapy) | Association of Progression Free Survival (PFS) With Ktrans and ADC | 5.100 month |
Secondary
Change in Pain Scale Between 12 Weeks and Baseline
Pain scores are measured at baseline and weeks 12, and 24. Change between baseline and 12 weeks are reported . In the pain score ranged from 0 to 10. 10 denotes most pain.
Time frame: baseline,12 weeks
Population: At 12 weeks, 3 individual have missing pain score data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment (Enzyme Inhibitor Therapy) | Change in Pain Scale Between 12 Weeks and Baseline | -1.35714 score on a scale | Standard Deviation 3.77455 |
p-value: 0.5828t-test, 2 sided
Secondary
Change of PSA Between 12 Weeks and Baseline
PSA at weeks 0, 12, and 24 were collected. Change between baseline and 12 weeks are reported
Time frame: baseline, 12 weeks
Population: At 12 weeks, 4 individual have missing PSA data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment (Enzyme Inhibitor Therapy) | Change of PSA Between 12 Weeks and Baseline | 453.04 ng/mL | Standard Deviation 998.62 |
p-value: 0.2006t-test, 2 sided
Secondary
Changes in Bone Scan Response
Bone Scan Response at weeks 2, 12, and 24 were collected. Change between baseline and 2 weeks are reported Bone Scan Response were measured as increase, decrease, or stable of bone lesions and scored as 1, -1, or 0, respectively, where higher values represent a worse outcome.
Time frame: baseline, 2 weeks
Population: 6 individual have missing bone lesions data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment (Enzyme Inhibitor Therapy) | Changes in Bone Scan Response | -0.43750 score on a scale | Standard Deviation 0.72744 |
p-value: 0.3291t-test, 2 sided
Secondary
Correlation of Percent Change in the Functional MRI Metrics to RECIST Tumor Measurements
The protocol proposed to collect RECIST tumor measurements at weeks 0, 12, and 24. However, the data were not collected
Time frame: baseline, 12 weeks, and 24 weeks
Population: Data on RECIST tumor measurements were not collected
Secondary
Correlation of Percent Change in the Functional MRI Metrics With CTC
The protocol proposed to collect CTC measurements at weeks 0, 12, and 24. However, the data were not collected
Time frame: baseline, 12 weeks, and 24 weeks
Population: data on CTC were not collected