Clinical Trial for Prostate Cancer: 07-C-0106: 1.888.NCI.1937

A Randomized Phase 2.5 Study of [153]Sm-EDTMP (Quadramet) With or Without a PSA TRICOM Vaccine in Men With Androgen-Insensitive Metastatic Prostate Cancer

Protocol # 07-C-0106

Why is this trial important?
Who is eligible for this trial?
What types of drugs or therapies are being used?
What is the treatment plan?
What is the frequency and duration of the visits?
What are the costs?
Who is the Principal Investigator?
Where is this trial taking place?
Who are the contacts for this trial?
Where can additional information be found?

Why is this trial important?

Previous studies have shown that PSA-TRICOM vaccines can stimulate immune and clinical responses in patients with metastatic prostate cancer. However, many cancer cells seem to be able to evade this immune response. Recent studies have shown that delivering radiation directly to the tumor can make it easier for the immune system to recognize and kill tumor cells—basically highlighting the cancer for the immune system. Quadramet is a radioactive drug that is engineered to specifically bind to bone metastasis and has been approved by the FDA to relieve pain in such tumors. Research has shown that standard doses can "highlight" the cancer, thus potentially improving the effectiveness of the vaccine. No therapies have been shown to improve disease control or survival in prostate cancer patients with prior chemotherapy. The goal of this trial is to see if vaccine with Quadramet can improve time to disease progression compared with Quadramet alone.

Who is eligible for this trial? (PDQ)

Histologically confirmed prostate cancer

Metastatic androgen independent disease with at least 2 bone lesions consistent with prostate cancer metastasis
Progressive disease defined by 1 of the following criteria:

Two rising PSA values separated by ≥ 1 week
New or enlarging lesions consistent with prostate cancer
Clinical progression

Previously treated with docetaxel for metastatic disease, unless unable to tolerate docetaxel
Concurrent medical castration therapy with testosterone-suppressing therapy (e.g., gonadotropin releasing hormone agonist) required unless patient has had prior surgical castration
Patients with soft tissue lesions thought to be due to prostate cancer, identified below, will not be eligible:

Hepatic lesions
Parenchymal lung lesions > 1 cm
Lymph node lesions > 3 cm
Other soft tissue lesions > 2 cm

No brain metastasis
No prior recombinant fowlpox-TRICOM vaccine or recombinant vaccinia-TRICOM vaccine; no prior samarium Sm 153 lexidronam pentasodium
No prior splenectomy
No systemic steroid or steroid eye drops within the past 2 weeks
Recovered from prior therapy, including surgery
≥ 18 years of age
ECOG 0–1
Granulocyte count ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
Hemoglobin ≥ 10 g/dL
AST and ALT < 2.5 x upper limit of normal (ULN)
Bilirubin < 1.5 mg/dL (≤ 3.0 mg/dL in patients with Gilbert's syndrome)
Creatinine normal OR creatinine clearance > 60 mL/min
Proteinuria < 1+ OR urine protein < 1,000 mg/24 hours
No other active malignancies within the past 12 months (with the exception of nonmelanoma skin cancers or carcinoma in situ of the bladder)
No life-threatening illnesses
No HIV, hepatitis B, or hepatitis C positivity
No autoimmune disease that requires or has required treatment
No concurrent medical conditions that would preclude study participation

What types of drugs or therapies are being used?

An experimental vaccine called PSA/ TRICOM can trigger the immune system to make cells that may be able to recognize and attack cancer cells that make PSA.
GM-CSF is an approved drug that helps stimulate the immune response to the vaccine.
Sm-EDTMP is an approved radioisotope: a type of radiation that has been approved to treat pain associated with cancer that has spread to bone. It is given by vein and targets tumors within bone. In this trial it is used to increase the level of certain proteins, making it easier for the immune system to identify and kill tumor cells.

What is the treatment plan? (PDQ)

This is a randomized, open-label, pilot study.

Patients will be randomized to 1 of the 2 treatment arms:

Arm I:

Patients receive ¹⁵³Sm-EDTMP IV over one minute on Day 8
Treatment with ¹⁵³Sm-EDTMP will be repeated every 12 weeks in the absence of disease progression or unacceptable toxicity

Arm II:

Patients receive PROSTAC-V/TRICOM subcutaneously (SC) on Day 1
Patients also receive ¹⁵³SM-EDTMP as in Arm I
Patients receive PROSTVAC-F/TRICOM vaccine SC on Days 15 and 29
Patients receive sargramostim (GM-CSF) SC on Days 1−4, 15−18, and 29−32
Treatment with recombinant fowlpox-TRICOM vaccine and GM-CSF repeats every 4 weeks in the absence of disease progression or unacceptable toxicity

Patients who are HLA-A2-positive undergo apheresis for immunological studies
Blood serum is analyzed for interferon gamma-releasing T cells specific to prostate-specific antigen (PSA)-3A as measured by ELISPOT assay as well as antibodies to PSA, vaccinia, fowlpox, and antinuclear antibody titer
Bone pain is assessed periodically
After completion of study treatment, patients are followed periodically for up to 15 years

What is the frequency and duration of the visits?

The initial new patient screening evaluation visit is usually 1 to 2 days. If patients wish to enroll at the screening visit, the need to complete baseline testing may extend the initial visit to 3 to 4 days. Follow-up visits are 1 to 2 days. All procedures are done on an outpatient basis.

What are the costs?

There is no charge for medical care received at the National Institutes of Health (NIH) Clinical Center. Patients will be responsible for travel costs for their initial screening visits. In most cases, once patients are enrolled in a trial, the National Cancer Institute (NCI) will pay the transportation costs for all subsequent trial-related visits for patients who do not live in the local area. In addition, these patients will receive a small per diem to help offset the costs of meals and lodging if they are being treated as outpatients.

It will be important to maintain your current insurance plan to cover all medical care that is provided away from the NIH Clinical Center.

No U.S. citizen or permanent U.S. resident residing in the U.S. who otherwise meets the eligibility requirements will be denied enrollment in clinical research protocols because of their inability to pay the costs of travel and subsistence.

Who is the Principal Investigator?

Dr. James L. Gulley is a board certified medical oncologist and Director of the Clinical Immunotherapy Group at the Laboratory of Tumor Immunology and Biology at the National Cancer Institute. He is a clinical investigator within the Medical Oncology Branch. He received his medical training at Loma Linda University in their medical scientist training program where he obtained a Ph.D. with his work in tumor immunology as well as an M.D. He went to Emory University for a residency in Internal Medicine and then to the National Cancer Institute for a fellowship in Medical Oncology. Following his fellowship, he was retained as senior staff within the NCI. Dr. Gulley has been running clinical trials in prostate cancer immunotherapy since 1999 and is an internationally recognized expert in this field

Where is this trial taking place?

NIH Clinical Center
National Institutes of Health
NCI Laboratory of Tumor Immunology and Biology
10 Center Drive
Bethesda, MD 20892

Who are the contacts for this trial?

James L. Gulley, M.D., Ph.D., F.A.C.P.
Principal Investigator
Phone: 301-435-2956
gulleyj@mail.nih.gov

Referrals:

Laura D. Otten, R.N., B.S.N., O.C.N.
Medical Oncology Referral Coordinator
Phone: 301-451-1228
1-866-611-6310 (Toll free)
Fax: 301-480-0919
ottenl@mail.nih.gov

Mary Pazdur, C.R.N.P.
Nurse Practitioner
Phone: 301-496-7870
Fax: 301-480-5094
pazdurm@mail.nih.gov