Vaccine and Antibody Treatment of Prostate Cancer

Prostatic Neoplasms Clinical Trial

Official title: Phase I Trial of a PSA Based Vaccine and an Anti-CTLA-4 Antibody in Adults With Metastatic Androgen Independent Prostrate Cancer

Status Completed

Clinical Trial Summary

This study will evaluate the side effects of a fixed dose of vaccine and GM-CSF with increasing doses of anti-CTLA-4 antibody in patients with advanced prostate cancer. The vaccine consists of a "priming vaccine" called PROSTVAC/TRICOM, made from vaccinia virus, and a "boosting vaccine" called PROSTVAC-F/TRICOM, made from fowlpox virus. GM-CSF is a chemical that boosts the immune system, and anti-CTLA-4 antibody is a protein that may improve anti-tumor activity and the response to the vaccines. DNA is inserted into the priming and boosting vaccine viruses to cause production of proteins that enhance immune activity and also to produce prostate specific antigen (PSA)-a protein that is normally produced by the patient's tumor cells.

Patients 18 years of age and older with androgen-insensitive prostate cancer that has spread beyond the original site may be eligible for this 7-month study. Candidates must have disease that has worsened despite treatments with hormones and up to one chemotherapy regimen. Their tumor must produce PSA, and they must have no history of allergy to eggs or egg products Candidates are screened with a medical history and physical examination, blood and urine tests, electrocardiogram, pathological confirmation of the diagnosis and presence of the PSA marker, chest x-rays, imaging studies to assess the extent of tumor, and, if clinically indicated, a cardiologic evaluation.

Participants receive the priming vaccination on study day 1. After 2 weeks and then again every 4 weeks while on the study, they receive a boosting vaccine. All vaccines are injected under the skin. On the day of each vaccination and daily for the next 3 days, patients receive an injection of GM-CSF to increase the number of immune cells at the vaccination site. On the day of the first six boosting vaccinations, they receive anti-CTLA-4 antibody as an infusion through a vein over 90 minutes.

Patients are monitored for safety and treatment response with the following tests and procedures:

• Blood and urine tests monthly, or more often if needed, to monitor liver, kidney, and other organ function.

• Imaging studies to assess the tumor before starting treatment, again around study days 99 and 183, and then every 3 months after that while on study.

• Apheresis (a procedure for collecting immune cells called lymphocytes) to measure the immune response to treatment. Apheresis is done three times: before starting the study and again around study days 99 and 183. For this procedure, blood is collected through a needle in an arm vein. The blood circulates through a machine that separates it into its components by spinning, and the lymphocytes are extracted. The rest of the blood is returned to the patient through the same needle. This will only be done in participants who have the tissue marker HLA-A2 (about 50% of patients).

Patients whose disease responds to treatment and who do not develop severe side effects may continue treatment beyond the initial 7-month study period on vaccine alone (without the antibody). After treatment is completed, patients are monitored for up to 15 years. This includes a medical history and physical examination for 5 years following the last vaccination. Information beyond 5 years is collected once a year by telephone.

Clinical Trial Description

Background:

• Adenocarcinoma of the prostate is the most common cancer diagnosis in American males, and the second leading cause of cancer death.

• The proposed vaccine strategy represents a third-generation design that elicits a T-cell immune response to cells expressing PSA and has been shown to break tolerance to this self-antigen, and cause objective response and PSA declines in patients with metastatic AIPC.

• This strategy also utilizes an antibody to CTLA-4 that may block the normal signals to down regulate the immune response following active vaccination.

• Anti CTLA-4 antibodies have been associated with autoimmune events that are generally manageable and have been associated with clinical response.

Objectives:

• To determine the safety and tolerability of a combination of a fixed dose of vaccine and anti-CTLA4, which will be dose escalated.

• To evaluate immunologic response (as measured by an increase in PSA specific T-cells measured by ELISPOT in HLA-A2+ patients), and clinical response (as measured by RECIST and PSA consensus criteria).

Eligibility:

• Must have metastatic androgen insensitive prostate cancer with no bone pain requiring narcotics and have had no more prior chemotherapy.

• Life expectancy greater than or equal to 6 months. ECOG 0-1

• Should have no autoimmune diseases; no evidence of being immunocompromised; no serious intercurrent medical illness; no cardiac disease; no prior splenectomy.

• No prior treatment with MDX-010 (Ipilimumab).

• No brain metastasis, history of seizures, encephalitis, or multiple sclerosis.

• No serious hypersensitivity reaction to egg products.

Design:

• This is an open label, phase I safety trial with sequential cohorts of patients all receiving a fixed dose of PSA-TRICOM vaccines and sargramostim, with dose escalation of MDX-010 (Ipilimumab).

• PROSTVAC -V/TRICOM (vaccinia) 2 x 10(8) pfu subcutaneously will be administered as the initial priming vaccine on day 1 of cycle 1 only.

• PROSTVAC -F/TRICOM (fowlpox) 1 x 10(9) pfu subcutaneously starting on day 15 followed by monthly boosting vaccination. Sargramostim 100 mcg per day will be administered subcutaneously at the vaccination site on days 1-4 of each vaccine cycle (prime and boost).

• MDX-010 (Ipilimumab) will be administered, as per the assigned dose level, as a 90-minute intravenous infusion on the same day as the monthly boosting vaccinations with PROSTVAC-F/TRICOM (fowlpox). After 6 courses of MDX-010, patients may receive Maintenance dose of MDX-010 every 3 months until there is evidence of disease progression or toxicity, for up to an additional 12 months (equivalent to 4 additional MDX-010 courses).

• Monthly boosting vaccinations with PROSTVAC-F/TRICOM (fowlpox) and sargramostim may then continue until patients meet off study criteria. ;

Related Conditions & MeSH terms

• Prostatic Neoplasms

• NCT number: NCT00113984
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Completed
• Phase: Phase 1
• Start date: June 8, 2005
• Completion date: December 1, 2011