Metastatic Castration-resistant Prostate Cancer
Conditions
Brief summary
This is a pilot phase 2 single-arm study, of men with metastatic castration-resistant prostate cancer (mCRPC). Patients will be treated with any of the approved life-prolonging therapies: abiraterone 1000 mg daily plus prednisone 5 mg (or dexamethasone 0.5 mg) daily, enzalutamide 160 mg daily, or docetaxel 50 mg/m2 every two weeks or 75 mg/m2 every three weeks.
Detailed description
Prostate cancer is a hormonally-driven disease and androgens are key in the growth of both normal prostate and prostate cancer cells. Once mCRPC is evident, most patients receive a second-generation hormonal therapy to further suppress the synthesis or androgens (abiraterone) and to block androgen receptor (AR) activation, nuclear translocation and DNA binding (enzalutamide). Conventional imaging of prostate cancer has limitations in staging, restaging after biochemical relapse, and response assessment. Functional imaging with positron emission tomography (PET) can target various aspects of tumor biology and is clearly superior in the detection of extra-prostatic disease. 18F-fluciclovine is a synthetic amino acid transported across mammalian cell membranes by amino acid transporters that are upregulated in prostate cancer cells. 18F-fluciclovine is approved for PET imaging to identify sites of prostate cancer recurrence in men with rising prostate specific antigen (PSA) following prior definitive treatment. This study describes the changes in 18F-fluciclovine PET scan and compare these results with PSA and conventional computerized tomography (CT) and bone scans, in mCRPC patients treated with abiraterone acetate-prednisone, enzalutamide or docetaxel.
Interventions
DRUG18F-fluciclovine PET Scan
The use of 18F-fluciclovine PET scanning will allow a more sensitive assessment of mCRPC patients at the initiation of systemic therapy and changes observed in 18F-fluciclovine PET will correlate better with the serologic changes in PSA, allowing superior disease monitoring, as compared to conventional imaging modalities. In addition, 18F-fluciclovine PET will detect heterogeneity in disease response and thus identify potential lesions amenable to targeted therapy.
Sponsors
Blue Earth Diagnostics
Tulane University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Intervention model description
Describe the changes in the 18F-fluciclovine Positron Emission Tomography (PET) in patients with metastatic castration resistant prostate cancer treated with abiraterone acetate-prednisone, enzalutamide or docetaxel.
Eligibility
Sex/Gender
MALE
Age
18 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
1. Eastern Cooperative Oncology Group (ECOG) Performance status 0-2; 2. Age ≥ 18 years; 3. Histologically confirmed adenocarcinoma of the prostate; 4. Ongoing use of luteinizing hormone-releasing hormone (LHRH) required in the absence of surgical castration and castrate concentration of testosterone (\< 50 ng/dL); 5. Detectable PSA of at least 2 ng/dL; 6. Metastatic disease documented by CT or bone scan within 42 days of cycle 1 day 1; 7. Life expectancy of ≥ 6 months; 8. Must have disease progression despite a castrate concentration of testosterone of \< 50 ng/dL based on: A. PSA progression defined as increase in PSA of at least 2 ng/dL and 25% from nadir values of prior therapy, determined by 2 separate measurement taken at least 1 week apart; And/or B. Radiographic disease progression based on response evaluation criteria in solid tumors (RECIST) 1.1 for soft tissue disease and/or prostate cancer working group 3 (PCWG3) for bone only disease; 9. No prior life-prolonging therapies for mCRPC are allowed, except Sipuleucel-T; 10. The use of docetaxel in the metastatic hormone-sensitive prostate cancer (mHSPC) setting is allowed; 11. Low dose prednisone (10 mg or less) or equivalent is allowed; 12. Acceptable liver function (within 28 days from enrollment) defined as: A. Bilirubin \< 2.5 times upper limit of normal (ULN), except for patients with known Gilbert disease (in such cases bilirubin \< 5 times ULN); B. AST (SGOT) and ALT (SGPT) \< 3 times ULN 13. Acceptable renal function (within 28 days from enrollment): A. Serum creatinine ≤ 2.0 x ULN or creatinine clearance ≥ 30 mL/min 14. Acceptable hematologic status (within 28 days from enrollment): A. Absolute neutrophil count (ANC) ≥ 1000 cell/mm3 (100 x 109/L) B. Platelet count ≥ 100,000 platelet/mm3 (100 x 109/L) C. Hemoglobin ≥ 9 g/dL 15. At least 2 weeks since prior radiation before starting study treatment (cycle 1 day 1); 16. Able to understand and willing to sign a written informed consent document; 17. Patients who have partners of childbearing potential must be willing to use a method of birth control with adequate barrier protection as determined to be acceptable by the principal investigator and sponsor during the study and for 1 week after last dose of abiraterone acetate.
Exclusion criteria
1. Pathological findings consistent with small cell carcinoma of the prostate; 2. Prior treatment with docetaxel for metastatic castration-resistant prostate cancer (CRPC); 3. Patient with normal 18F-flucicolovine PET/CT scans at baseline; 4. Know allergies, hypersensitivity, or intolerance to abiraterone, prednisone, 18F-fluciclovine or their excipients; 5. Any chronic medical condition requiring ≥ 10 mg daily of systemic prednisone (or equivalent); 6. Major surgery (e.g., required general anesthesia) within 2 weeks before screening; 7. Uncontrolled active infection (including hepatitis B or C or AIDS). Patients with hepatitis B/C who have disease under control and no significant liver function impairment, and undetectable viral load will be allowed to participate. Similarly, patients with known HIV and ≥ 400 CD4 + T cells are allowed to participate; 8. Evidence of other metastatic malignancies within the last year; 9. Evidence of serious and/or unstable pre-existing medical, psychiatric or other condition (including laboratory abnormalities) that could interfere with patient safety or provision of informed consent to participate in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in 18F-fluciclovine PET Scan for Patients With mCRPC on Treatment With Life Prolonging Therapies | 12 weeks | To describe the 18F-fluciclovine PET findings for patients with mCRPC prior to starting treatment with Life Prolonging Therapies, and at 12 weeks after Life Prolonging Therapies treatment initiation. We have 4 categories that can be seen in the scan to measure the metabolic response using PERSIST 1.1, 1)stable disease, 2)progressive disease, 3)partial response and 4)complete response. |
| PET Scan vs. Conventional CT and Bone Scan | 12 weeks | A comparison of 18F-fluciclovine PET with conventional CT and bone scans for patients with mCRPC prior to starting treatment with life prolonging therapies, and at 12 weeks after starting life prolonging therapies; and to correlate these changes with PSA response and progression after starting life prolonging therapies. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 18F-fluciclovine PET Scan Single intravenous administration of 18F-fluciclovine for PET Scan.
18F-fluciclovine PET Scan: The use of 18F-fluciclovine PET scanning will allow a more sensitive assessment of mCRPC patients at the initiation of systemic therapy and changes observed in 18F-fluciclovine PET will correlate better with the serologic changes in PSA, allowing superior disease monitoring, as compared to conventional imaging modalities. In addition, 18F-fluciclovine PET will detect heterogeneity in disease response and thus identify potential lesions amenable to targeted therapy. | 9 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | 18F-fluciclovine PET Scan |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Age, Continuous | 62.56 Years STANDARD_DEVIATION 11.07 |
| Alkaline phosphatase | 95.78 IU/L STANDARD_DEVIATION 35.82 |
| Calcium | 9.31 mg/dL STANDARD_DEVIATION 0.5 |
| Creatinine | 1.15 mg/dL STANDARD_DEVIATION 0.56 |
| Haemoglobin | 12.23 g/dL STANDARD_DEVIATION 1.73 |
| Platelets | 257.56 cells/mcL STANDARD_DEVIATION 105.58 |
| Prostate-Specific Antigen | 150 ng/mL STANDARD_DEVIATION 399 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 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 | 5 Participants |
| Region of Enrollment United States | 9 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 9 Participants |
| Testosterone Testosterone detectable | 1 Participants |
| Testosterone Testosterone undetectable | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 9 |
| other Total, other adverse events | 0 / 9 |
| serious Total, serious adverse events | 0 / 9 |
Outcome results
Primary
Changes in 18F-fluciclovine PET Scan for Patients With mCRPC on Treatment With Life Prolonging Therapies
To describe the 18F-fluciclovine PET findings for patients with mCRPC prior to starting treatment with Life Prolonging Therapies, and at 12 weeks after Life Prolonging Therapies treatment initiation. We have 4 categories that can be seen in the scan to measure the metabolic response using PERSIST 1.1, 1)stable disease, 2)progressive disease, 3)partial response and 4)complete response.
Time frame: 12 weeks
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 18F-fluciclovine PET Scan | Changes in 18F-fluciclovine PET Scan for Patients With mCRPC on Treatment With Life Prolonging Therapies | Stable disease | 5 Participants |
| 18F-fluciclovine PET Scan | Changes in 18F-fluciclovine PET Scan for Patients With mCRPC on Treatment With Life Prolonging Therapies | Progressive disease | 0 Participants |
| 18F-fluciclovine PET Scan | Changes in 18F-fluciclovine PET Scan for Patients With mCRPC on Treatment With Life Prolonging Therapies | Partial response | 3 Participants |
| 18F-fluciclovine PET Scan | Changes in 18F-fluciclovine PET Scan for Patients With mCRPC on Treatment With Life Prolonging Therapies | Complete response | 0 Participants |
Primary
PET Scan vs. Conventional CT and Bone Scan
A comparison of 18F-fluciclovine PET with conventional CT and bone scans for patients with mCRPC prior to starting treatment with life prolonging therapies, and at 12 weeks after starting life prolonging therapies; and to correlate these changes with PSA response and progression after starting life prolonging therapies.
Time frame: 12 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 18F-fluciclovine PET Scan | PET Scan vs. Conventional CT and Bone Scan | PET scan positivity | 8 Participants |
| 18F-fluciclovine PET Scan | PET Scan vs. Conventional CT and Bone Scan | Conventional CT scan positivity | 3 Participants |
| 18F-fluciclovine PET Scan | PET Scan vs. Conventional CT and Bone Scan | Conventional bone scan positivity | 8 Participants |
| 18F-fluciclovine PET Scan | PET Scan vs. Conventional CT and Bone Scan | PSA response | 3 Participants |