Background:
Androgen deprivation therapy (ADT) and surveillance are treatment options for prostate cancer
patients with biochemical progression after localized therapy with either definitive
radiation or surgery (biochemically recurrent prostate cancer). A primary goal in these
patients is to prevent morbidity from their cancer that results from disease progression and
metastatic disease on conventional imaging.
Radium-223 has demonstrated the ability to improve survival in men with symptomatic
metastatic castration resistant prostate cancer (mCRPC) with a manageable toxicity profile,
particularly in patients who have not yet received docetaxel.
Radiation, even at low doses can impact immune recognition and immune cell killing of cancer
cells. Recent findings by the LTIB suggest that radium-223 potentiated T-cell killing of
prostate cancer cells.
Radium-223 may present an alternative option for patients with BRPC that is not associated
with substantial toxicity (as seen with ADT) and may have a lasting effect due to its
potential effect on the immune system and/or the bone microenvironment.
Emerging PET imaging studies will likely find evidence of micrometastatic disease, often in
the bones, in biochemically recurrent prostate cancer patients, although these patients will
have no standard of care that can be supported by prospective data.
Radium-223 has demonstrated the ability to improve survival in men with symptomatic prostate
cancer, but it remains unknown what the impact is in patients with micrometastatic or PET
positive prostate cancer in their bones
Preclinical data has suggested that radium-223 can impact the immune system.
In addition, changes in PSA kinetics, changes on PET scan findings, and safety and
tolerability of radium-223 in this population will also be evaluated.
Objective:
To determine statistically significant changes in immune cell populations compared to
baseline in participants with biochemically recurrent or 18F NaF PET scan positive prostate
cancer treated with radium-223
Eligibility:
Histologically confirmed adenocarcinoma of the prostate
Imaging showing positive findings on NaF PET, negative CT Scan and Tc-99m Bone Scan
Detectable PSA
ECOG 0-1
Design:
Single arm study
Participants will receive 6 injections of radium-223 with monthly assessments of PSA and
periodic immune response. NaF PET scans will be completed at screening then at 4 and 7 months
after the start of radium-223.
After completion of treatment participant will be followed every 6 (+/- 2 weeks).
- INCLUSION CRITERIA:
- Histopathological confirmation of prostate adenocarcinoma confirmed in either the
Laboratory of Pathology at the National Institutes of Health (NIH) Clinical Center, or
Walter Reed National Military Medical Center prior to enrollment. If no pathologic
specimen is available, participants may enroll with a pathologist s report showing a
histologic diagnosis of prostate cancer and a clinical course consistent with the
disease.
- Biochemical progression after definitive surgery or radiation define as follows:
- Participants must have a detectable PSA
- Negative CT scan/MRI and Tc99 bone scan for metastatic prostate cancer. (Only Tc99
will be used to detect bone lesions, CT/MRI would be used to detect soft tissue
lesions)
- Presence of findings on PET scan (i.e., NaF PET scan) suspicious for metastatic
prostate cancer in bone. Note: while lymph node findings would be allowed and provide
the opportunity for the assessment of any abscopal effects, PET scan findings
suggesting visceral disease will be excluded.
- Testosterone >= 100 ng/dL
- ECOG performance status of 0 1
- Recovery from acute toxicity related to prior therapy, including surgery and
radiation, (defined as no toxicity >= grade 2).
- Hematological eligibility parameters (within 16 days before treatment initiation):
- Granulocyte count >= 3,000/mm^3
- Absolute neutrophil count (ANC) >= 1,500/mm^3
- Platelet count >= 100,000/mm^3
- Hgb >= 10 g/dL
- Hepatic function eligibility parameters (within 16 days before treatment initiation)
-- Bilirubin <=1.5 mg/dL (OR in participants with Gilbert s syndrome, a total
bilirubin <= 3.0), AST and ALT <= 2.5 times upper limit of normal.
- Adequate renal function defined by eGFR within normal as predicted by the CKD-EPI
equation (>= 50 mL/min/1.73m^2) or by measure o f creatinine clearance from 24-hour
urine collection.
- No other active malignancies within 36 months of treatment initiation (with the
exception of nonmelanoma skin cancers or carcinoma in situ of the bladder)
- Participants must be >=18 years old. Currently, no dosing or adverse event data is
available on the use of radium in participants < 18 years of age; therefore, only
adults are included in this study.
- Ability of subject to understand and the willingness to sign a written informed
consent document.
- The effects radium-223 on the developing human fetus are unknown but based on the
mechanism of action, radium-223 has the potential to cause fetal harm. For this
reason, men must agree to use condoms for the duration of study therapy and at least 6
months
after the last treatment administration. Female partners of reproductive potential must use
a highly effective method of birth control during treatment and for 6 months after their
partner s last treatment administration. Should a woman become pregnant or suspect she
is pregnant while her partner is participating in this study, she should inform her
treating physician immediately.
EXCLUSION CRITERIA:
- Participants with immunocompromised status due to Human Immunodeficiency Virus (HIV)
infection or other immunodeficiency diseases because this is a trial with a primary
endpoint looking at immune response, requiring functional immune systems.
- Participants who test positive for HBV or HCV.
- Chronic administration (defined as daily or every other day for continued use > 14
days) of systemic corticosteroids within 28 days of treatment initiation. Use of
corticosteroids with minimal systemic absorption (e.g., inhaled steroids, nasal
sprays, intraarticular, and topical agents) is allowed.
- Receipt of any organ transplantation, including allogeneic stem-cell transplantation,
but with the exception of transplants that do not require immunosuppression (e.g.
corneal transplant, hair transplant).
- Serious intercurrent medical illness that, in the judgement of the investigator, would
interfere with participant's ability to carry out the treatment program.
- Subjects required other medications known to alter PSA including 5-alpha reductase
inhibitors (finasteride and dutasteride) and alternative therapies (e.g.,
phytoestrogens and saw palmetto).
- History of prior chemotherapy.
- History of prior systemic therapy with radionuclides (e.g., strontium-89,
samarium-153, rhenium-186, rhenium-188, or radium 223 dichloride).
- Receipt of an investigational agent within 28 days (or 56 days for an antibody-based
therapy) of treatment initiation.
- Major surgery within 28 days prior to treatment initiation.
- PET scan findings suggesting visceral disease.
