NCT00113984

Vaccine and Antibody Treatment of Prostate Cancer

Completed Phase 1 Last updated 16 December 2019

What this trial tests

Phase 1 trial testing PROSTVAC-V/TRICOM in Prostatic Neoplasms in 30 participants. Completed in 1 December 2011.

Timeline

8 June 2005

Primary endpoint
1 February 2008

1 December 2011

Quick facts

Lead sponsor	National Cancer Institute (NCI)
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Primary purpose	treatment
Enrollment	30
Start date	8 June 2005
Primary completion	1 February 2008
Estimated completion	1 December 2011
Sites	1 location across United States

Drugs / interventions tested

• PROSTVAC-V/TRICOM — full drug profile →
• PROSTVAC-F/TRICOM
• MDX-010 — full drug profile →
• Sargramostim (SARGRAMOSTIM) — full drug profile →

Conditions studied

• Prostatic Neoplasms — all drugs for Prostatic Neoplasms →

Sponsor

National Cancer Institute (NCI)

Who can join

Adults 18 to 85, male only, with Prostatic Neoplasms. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Ipilimumab and a poxviral vaccine targeting prostate-specific antigen in metastatic castration-resistant prostate cancer: a phase 1 dose-escalation trial.
   Madan RA, Mohebtash M, Arlen PM, Vergati M, et al · · 2012 · cited 254× · PMID 22326924 · DOI 10.1016/s1470-2045(12)70006-2
2. Antigen-specific vaccines for cancer treatment.
   Tagliamonte M, Petrizzo A, Tornesello ML, Buonaguro FM, et al · · 2014 · cited 109× · PMID 25483639 · DOI 10.4161/21645515.2014.973317
3. Immune impact induced by PROSTVAC (PSA-TRICOM), a therapeutic vaccine for prostate cancer.
   Gulley JL, Madan RA, Tsang KY, Jochems C, et al · · 2014 · cited 104× · PMID 24778277 · DOI 10.1158/2326-6066.cir-13-0108
4. Overcoming drug resistance and treating advanced prostate cancer.
   Semenas J, Allegrucci C, Boorjian SA, Mongan NP, et al · · 2012 · cited 78× · PMID 22746994 · DOI 10.2174/138945012802429615
5. A combination trial of vaccine plus ipilimumab in metastatic castration-resistant prostate cancer patients: immune correlates.
   Jochems C, Tucker JA, Tsang KY, Madan RA, et al · · 2014 · cited 75× · PMID 24514956 · DOI 10.1007/s00262-014-1524-0
6. AR function in promoting metastatic prostate cancer.
   Augello MA, Den RB, Knudsen KE. · · 2014 · cited 72× · PMID 24425228 · DOI 10.1007/s10555-013-9471-3
7. Immune Checkpoint Inhibitors in Prostate Cancer.
   Venkatachalam S, McFarland TR, Agarwal N, Swami U. · · 2021 · cited 71× · PMID 34063238 · DOI 10.3390/cancers13092187
8. Soluble CD27-pool in humans may contribute to T cell activation and tumor immunity.
   Huang J, Jochems C, Anderson AM, Talaie T, et al · · 2013 · cited 61× · PMID 23677477 · DOI 10.4049/jimmunol.1300022