Prostate Cancer
Conditions
Keywords
liver metastasis, lung metastasis, metastatic castrate-resistant, prostate cancer
Brief summary
This research study is being done to measure the clinical benefit associated with cabozantinib (XL184) in men who have prostate cancer that has spread to visceral organs (organs other than bone or lymph nodes) and no longer responds to initial hormonal (castration) therapy. This type of prostate cancer is called metastatic, castrate-resistant prostate cancer.
Detailed description
Cabozantinib (XL184), a multi-targeted tyrosine kinase inhibitor, has demonstrated a powerful clinical phenotype in men with metastatic castrate resistant prostate cancer (mCRPC) both before and after chemotherapy. This phenotype consists of rapid reduction in pain (when present) and improvement in bone scans that may or may not be accompanied by decrease in serum prostate specific antigen (PSA) concentrations. In previous studies of cabozantinib in advanced prostate cancer, patients with visceral disease have been excluded. Hence, this protocol creates a unique opportunity to define the activity of this disease in the population of men with visceral disease - a marker for poorer prognosis in mCRPC. Primary Objectives: \- To assess the clinical benefit (complete response + partial response + stable disease) of cabozantinib in patients with mCRPC with visceral metastases. Secondary Objectives: * To assess the impact of cabozantinib on numbers live circulating tumor cells (CTCs) using NanoVelcro Chips * To test the feasibility of measuring variation in gene expression in circulating tumor cells (CTCs) in response to therapy. * To determine if there is an impact of cabozantinib on live circulating tumor cell (CTC) number and patterns of gene expression. * To measure the impact of cabozantinib on serum HGF (hepatocyte growth factor) and VEGF (vascular endothelial growth factor) levels in men with metastatic, castration-resistant prostate cancer (mCRPC). * To assess the safety and tolerability of lower doses (i.e. doses below 100 mg daily) of cabozantinib in mCRPC with visceral involvement. * To collect blood, urine, tissue, and plasma which may be used determine if there are germline genetic variations that correlate with toxicity. * To pilot correlations between molecular content between circulating tumor cells (CTCs), large oncosomes, and tumor tissue.
Interventions
DRUGCabozantinib
Cabozantinib 60 mg daily (oral). Subjects may continue to receive study treatment until they experience unacceptable drug-related toxicity or disease progression.
Sponsors
Edwin Posadas, MD
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
KEY INCLUSION CRITERIA \- mCRPC that includes visceral disease. Visceral metastatic disease is defined as solid organ infiltration that is not bone or lymph node metastases. KEY
Exclusion criteria
* Recent history (\<6 months) of gastrointestinal hemorrhage requiring blood transfusion. * Tumor involvement in the intestinal lining which the treating physician deems at risk for perforation with rapid tumor response.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Benefit Rate From Cabozantinib (XL184) | Baseline to 12 weeks after starting therapy | Clinical benefit rate is defined as the combination of complete response, partial response, and stable disease as defined by modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by CT imaging and Prostate Cancer Working Group 2 (PCWG2) criteria. Complete response (CR) defined as disappearance of all target lesions; Partial response (PR) \>=30% decrease in som of diameters of target lesions (taking as reference the baseline), and stable disease, neither sufficient shrinkage to qualify for PR nor increase to qualify for progressive disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Number of Circulating Tumor Cells (CTC) in Response to Cabozantinib | Baseline and 12 weeks | Change in number of CTC from baseline at 12 weeks |
| Number of Patients With NanoVelcro Appropriate for RNA in Circulating Tumor Cells | 12 weeks | This is to provide a measure of feasibility using NanoVelcro to measure RNA in circulating tumor cells (CTC) |
| Change in Levels of Serum Hepatocyte Growth Factor (HGF) and Vascular Endothelial Growth Factor (VEGF) Concentration | 12 weeks | Mean change from baseline in levels of HGF and VEGF |
| Number of Participants With Grade 3/4 Adverse Events Related to Cabozantinib as Assessed Using CTCAE (v.4) | Every 2 weeks for first 3 Cycles and every 4 weeks thereafter for an expected average of 28 weeks. | Each cycle is 28 days. Safety and tolerability was defined as related grade 3-4 AEs of doses of cabozantinib below 100 mg daily using common terminology criteria for adverse events (CTCAE) |
| Number of Patients With Evaluable Protein Content of Large Oncosomes From Baseline to First Documented Progression or Date of Death | From baseline until the date of first documented progression or date of death from any cause, whichever comes first, assessed for an expected average of 28 weeks. | This is a feasibility outcome to assess ability to measure protein content in large oncosomes in this population. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Cabozantinib) Cabozantinib 60mg orally daily until disease progression
Cabozantinib: Cabozantinib 60 mg daily (oral). Subjects may continue to receive study treatment until they experience unacceptable drug-related toxicity or disease progression. | 17 |
| Total | 17 |
Baseline characteristics
| Characteristic | Treatment (Cabozantinib) |
|---|---|
| Age, Continuous | 65 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 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 | 1 Participants |
| Race (NIH/OMB) White | 16 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 | — / — |
| other Total, other adverse events | 17 / 17 |
| serious Total, serious adverse events | 14 / 17 |
Outcome results
Primary
Clinical Benefit Rate From Cabozantinib (XL184)
Clinical benefit rate is defined as the combination of complete response, partial response, and stable disease as defined by modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by CT imaging and Prostate Cancer Working Group 2 (PCWG2) criteria. Complete response (CR) defined as disappearance of all target lesions; Partial response (PR) \>=30% decrease in som of diameters of target lesions (taking as reference the baseline), and stable disease, neither sufficient shrinkage to qualify for PR nor increase to qualify for progressive disease.
Time frame: Baseline to 12 weeks after starting therapy
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Cabozantinib) | Clinical Benefit Rate From Cabozantinib (XL184) | 10 Participants |
Secondary
Change in Levels of Serum Hepatocyte Growth Factor (HGF) and Vascular Endothelial Growth Factor (VEGF) Concentration
Mean change from baseline in levels of HGF and VEGF
Time frame: 12 weeks
Population: HGF was evaluable in 16 patients who had viable research samples. VEGF was evaluable in 15 patients who had viable research samples.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment (Cabozantinib) | Change in Levels of Serum Hepatocyte Growth Factor (HGF) and Vascular Endothelial Growth Factor (VEGF) Concentration | -322.96 pg/ml | Standard Deviation 1981.19 |
| Treatment (Cabozantinib) VEGF Levels | Change in Levels of Serum Hepatocyte Growth Factor (HGF) and Vascular Endothelial Growth Factor (VEGF) Concentration | 191.1 pg/ml | Standard Deviation 302.1 |
Secondary
Change in Number of Circulating Tumor Cells (CTC) in Response to Cabozantinib
Change in number of CTC from baseline at 12 weeks
Time frame: Baseline and 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment (Cabozantinib) | Change in Number of Circulating Tumor Cells (CTC) in Response to Cabozantinib | 53.2 CTCs/7.5 ml | Standard Deviation 217.8 |
Secondary
Number of Participants With Grade 3/4 Adverse Events Related to Cabozantinib as Assessed Using CTCAE (v.4)
Each cycle is 28 days. Safety and tolerability was defined as related grade 3-4 AEs of doses of cabozantinib below 100 mg daily using common terminology criteria for adverse events (CTCAE)
Time frame: Every 2 weeks for first 3 Cycles and every 4 weeks thereafter for an expected average of 28 weeks.
Population: All patients
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment (Cabozantinib) | Number of Participants With Grade 3/4 Adverse Events Related to Cabozantinib as Assessed Using CTCAE (v.4) | Lipase increased | 2 Participants |
| Treatment (Cabozantinib) | Number of Participants With Grade 3/4 Adverse Events Related to Cabozantinib as Assessed Using CTCAE (v.4) | Lymphocyte count decreased | 3 Participants |
| Treatment (Cabozantinib) | Number of Participants With Grade 3/4 Adverse Events Related to Cabozantinib as Assessed Using CTCAE (v.4) | Rectal Fistula | 1 Participants |
| Treatment (Cabozantinib) | Number of Participants With Grade 3/4 Adverse Events Related to Cabozantinib as Assessed Using CTCAE (v.4) | AST increased | 4 Participants |
| Treatment (Cabozantinib) | Number of Participants With Grade 3/4 Adverse Events Related to Cabozantinib as Assessed Using CTCAE (v.4) | Alkaline phosphatase increased | 2 Participants |
| Treatment (Cabozantinib) | Number of Participants With Grade 3/4 Adverse Events Related to Cabozantinib as Assessed Using CTCAE (v.4) | Anemia | 1 Participants |
| Treatment (Cabozantinib) | Number of Participants With Grade 3/4 Adverse Events Related to Cabozantinib as Assessed Using CTCAE (v.4) | Corneal Epithelial Defect | 1 Participants |
| Treatment (Cabozantinib) | Number of Participants With Grade 3/4 Adverse Events Related to Cabozantinib as Assessed Using CTCAE (v.4) | Dehydration | 1 Participants |
| Treatment (Cabozantinib) | Number of Participants With Grade 3/4 Adverse Events Related to Cabozantinib as Assessed Using CTCAE (v.4) | Diarrhea | 1 Participants |
| Treatment (Cabozantinib) | Number of Participants With Grade 3/4 Adverse Events Related to Cabozantinib as Assessed Using CTCAE (v.4) | GGT increased | 1 Participants |
| Treatment (Cabozantinib) | Number of Participants With Grade 3/4 Adverse Events Related to Cabozantinib as Assessed Using CTCAE (v.4) | Hematuria | 1 Participants |
| Treatment (Cabozantinib) | Number of Participants With Grade 3/4 Adverse Events Related to Cabozantinib as Assessed Using CTCAE (v.4) | Hypertension | 1 Participants |
| Treatment (Cabozantinib) | Number of Participants With Grade 3/4 Adverse Events Related to Cabozantinib as Assessed Using CTCAE (v.4) | Hyponatremia | 2 Participants |
| Treatment (Cabozantinib) | Number of Participants With Grade 3/4 Adverse Events Related to Cabozantinib as Assessed Using CTCAE (v.4) | Palmar-Plantar Erythrodysesthesia | 1 Participants |
Secondary
Number of Patients With Evaluable Protein Content of Large Oncosomes From Baseline to First Documented Progression or Date of Death
This is a feasibility outcome to assess ability to measure protein content in large oncosomes in this population.
Time frame: From baseline until the date of first documented progression or date of death from any cause, whichever comes first, assessed for an expected average of 28 weeks.
Population: Only 12 samples were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Cabozantinib) | Number of Patients With Evaluable Protein Content of Large Oncosomes From Baseline to First Documented Progression or Date of Death | 12 Participants |
Secondary
Number of Patients With NanoVelcro Appropriate for RNA in Circulating Tumor Cells
This is to provide a measure of feasibility using NanoVelcro to measure RNA in circulating tumor cells (CTC)
Time frame: 12 weeks
Population: There were 16 patients evaluable for this outcome (1 patient did not have RECIST measurable disease)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Cabozantinib) | Number of Patients With NanoVelcro Appropriate for RNA in Circulating Tumor Cells | 16 Participants |