Clinical trial NCT04158245: 18F-fluciclovine PET in Metastatic Castration Resistant Prostate Cancer Treated With Life Prolonging Therapies
Official title: Changes in 18F-fluciclovine Positron Emission Tomography (PET) in Patients With Metastatic Castration Resistant Prostate Cancer Treated With With Life Prolonging Therapies: A Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Castration-resistant Prostate Cancer
Lead sponsor: Tulane University
Sponsor class: OTHER
Collaborators: name: Blue Earth Diagnostics
First posted: 2019-11-08
Enrollment: 10
Sex: MALE
Minimum age (years): 18
Maximum age (years): 18
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: OTHER

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Changes in 18F-fluciclovine PET scan for patients with mCRPC on treatment with Life Prolonging Therapies
timeFrame: 12 weeks
measure: PET scan vs. conventional CT and bone scan
timeFrame: 12 weeks
Secondary outcomes:
Other outcomes:
measure: Compare the PET scan results with the genomic alterations in circulating tumor deoxyribonucleic acid (ctDNA)
timeFrame: 12 weeks
Locations:
city: New Orleans
country: United States
facility: Tulane Cancer Center Clinic
state: Louisiana
Study officials:
affiliation: Tulane University School of Medicine
name: Brian Lewis, MD, MPH, FACP
role: PRINCIPAL_INVESTIGATOR
References: