Phase 2 N=44 Randomized Treatment

153Sm-EDTMP With or Without a PSA/TRICOM Vaccine To Treat Men With Androgen-Insensitive Prostate Cancer

Prostate Cancer

Bottom Line

View on ClinicalTrials.gov: NCT00450619 ↗

Enrolled (actual)

Serious AEs

23.3%

Results posted

Jul 2013

Primary outcome: Primary: Number of Patients With Stable Disease at 4 Months. — 2; 5 participants

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Samarium Sm 153 lexidronam pentasodium (Radiation); Sargramostim (Biological); Recombinant vaccinia-TRICOM vaccine (Biological); Recombinant fowlpox-TRICOM vaccine (Biological)
Age: Adult, Older Adult · 18+ yrs
Sex: Male
Sponsor: National Cancer Institute (NCI)
Primary completion: Nov 2012

Outcome Measures

Outcome	Result	p-value
PRIMARY Number of Patients With Stable Disease at 4 Months.	2; 5	—
PRIMARY Progression Free Survival (PFS)	1.7; 3.7	0.041 sig
SECONDARY Toxicity	19; 22	—
SECONDARY Number of Participants With Prostate-Specific Antigen (PSA) ≥ 30%	0; 4	—
SECONDARY Number of Participants With Prostate-Specific Antigen (PSA) ≥50%	0; 3	—
SECONDARY Overall Survival	8.1; 9.2	0.30
SECONDARY Arm A: Prostate-Specific Antigen (PSA) T-cell Responses Post-vs. Pre-treatment	0; 0; 0; 0; 0; 0	—
SECONDARY Arm B: Prostate-Specific Antigen (PSA) T-cell Responses Post-vs. Pre-treatment	0; 786; 0; 374; 5269; 453	—
SECONDARY Objective Response (Complete Response + Partial Response)	0; 0; 0; 0	—
SECONDARY Palliation: Pain at Baseline	10; 8	—
SECONDARY Palliation: Improvement in Baseline Pain	6; 5	—

Summary

Background: * No treatment is known to improve survival for prostate cancer patients who have not been helped by previous treatments with hormones and chemotherapy. * An experimental vaccine called prostate specific antigen (PSA)/TRICOM contains genes for a protein produced by prostate cancer cells called prostate-specific antigen (PSA). The vaccine can trigger the immune system to make cells that may be able to recognize and attack the cancer cells that make PSA. * Granulocyte macrophage colony stimulating factor (GM-CSF) is an approved drug that is usually given to increase a patient's white blood cell count or to stimulate the immune system. * 1Samarium-153-ethylene diamine tetramethylene phosphonate (53Sm-EDTMP) is a radioactive drug that has been approved for many years to treat advanced prostate cancer. It is given through a vein and can be targeted directly to tumors in the bone where it can relieve pain caused by bone lesions. Radiation also increases the level of certain proteins inside the tumor, making it easier for the immune system to find and kill the tumor cells. * When laboratory mice were given just vaccine, just radiation, or a combination of both, the combination was most effective in treating tumors. Objectives: -To determine if combined treatment with PSA/TRICOM vaccine and 153Sm-EDTMP radiation can delay progression of prostate cancer better than radiation alone. Eligibility: -Patients who have advanced prostate cancer that has worsened despite treatments with hormones, have two or more bone lesions related to their prostate cancer, and have had prior treatment with docetaxel chemotherapy. Design: * Patients are randomly assigned to receive radiation alone (Arm A) or radiation with vaccine and sargramostim (Arm B). * Arm A receives 153Sm-EDTMP radiation starting on study day 8 and repeated every 12 weeks. * Arm B receives a priming vaccine on study day 1 and radiation on day 8. Radiation therapy is repeated every 12 weeks. Boosting vaccines are given on days 15 and 29 and then monthly. GM-CSF is given with each vaccination (on the day of the vaccination and for the next 3 days) to enhance the immune response. Vaccinations and GM-CSF are given as injections under the skin, usually in the thigh. Radiation therapy is given through a vein. * Patients are monitored regularly with physical examinations, blood and urine tests, and scans to evaluate safety and treatment response. * Patients who are human leukocyte antigen serotype within HLA-A A serotype group (HLA-A2)-positive undergo apheresis, a procedure similar to donating blood, for obtaining immune cells called lymphocytes to measure the immune response to the vaccine.

Eligibility Criteria

INCLUSION CRITERIA:

A. Histopathological documentation of prostate cancer confirmed in the Laboratory of Pathology at the National Institutes of Health (NIH) Clinical Center, National Institutes of Health (NIH), the National Naval Medical Center, or Walter Reed Army Medical Center; or participating Institute's Department of Pathology prior to starting this study. If no pathologic specimen is available, patients may enroll with a pathologist's report showing a histologic diagnosis of prostate cancer and a clinical course consistent with the disease.

B. Must have metastatic castration resistant prostate cancer (CRPC) with at least 2 bone lesions consistent with prostate cancer metastasis and progressive disease (2 rising PSA values separated by at least one week, new or enlarging lesions consistent with prostate cancer, or clinical progression) on docetaxel for metastatic prostate cancer or inability to tolerate docetaxel.

C. Life expectancy greater than or equal to 6 months.

D. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

E. No systemic steroid or steroid eye drop use within 2 weeks prior to initiation of experimental therapy.

F. Hematological eligibility parameters (within 16 days of starting therapy).

Granulocyte count greater than or equal to 1,500/mm^3
Platelet (PLT) count greater than or equal to 100,000/mm^3
Hemoglobin (Hgb) greater than or equal to 10 Gm/dL (Transfusion may be given to accomplish this)

G. Biochemical eligibility parameters (within 16 days of starting therapy)

-Hepatic function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than 2.5 times upper limit of normal; bilirubin less than 1.5 mg/dL OR in patients with Gilbert's syndrome, a total bilirubin less than or equal to 3.0 mg/dL.

H. No other active malignancies within the past 12 months (with the exception of nonmelanoma skin cancers or carcinoma in situ of the bladder and treated with curative intent) or life-threatening illnesses.

I. Willing to travel to the National Institutes of Health (NIH) or participating Institute for follow-up visits.

J. 18 years of age or greater.

K. Able to understand and sign informed consent.

L. Agree to use adequate contraception prior to study entry and for at least 4 months following the last vaccine injection.

M. Patients must remain on medical castration therapy with testosterone-suppressing therapy (e.g., gonadotropin releasing hormone (GnRH) agonist), unless they have had surgical castration.

N. Patients must have recovered from acute toxicities related to prior therapy or surgery. For chemotherapy, typically this is 3 to 4 weeks.

O. Patients who are incontinent of urine should be willing to undergo bladder catheterization to minimize the risk of radioactive contamination of clothing, bed linen, and the patient's environment.

P. Concurrent treatment with bisphosphonates is allowed. If bisphosphonates have been given within 2 weeks prior to planned (153)Sm-EDTMP, then a 99Tc whole-body scintigraphy (bone scan) will be performed to confirm uptake into lesions. Bisphosphonates will not be given within 48 hours after (153)Sm-EDTMP administration.

Q. Serum creatinine less than or equal to 1.5 times upper limit of normal OR creatinine clearance on a 24-h urine collection of greater than or equal to 60 mL/min.

EXCLUSION CRITERIA

A. Patients should have no evidence, as listed below, of being immunocompromised:

Human immunodeficiency virus (HIV) positivity due to the potential for decreased tolerance and risk for severe side effects.
Hepatitis B or C positivity.
Concurrent use of topical steroids (including steroid eye drops) or systemic steroids. This is to avoid immunosuppression which may lead to potential complications with vaccinia (priming vaccination). Nasal or inhaled steroid use is permitted.

B. Patients should have no autoimmune diseases that have required treatment, such as Addison's disease, Hashimoto's thyroiditis, systemic

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Data sourced from ClinicalTrials.gov (NCT00450619). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.