A Phase II Study of Neoadjuvant rFowlpox-PSA (L155)-TRICOM (Prostvac-F/TRICOM) in Combination With rVaccinia-PSA (L155)-TRICOM (Prostvac-V/TRICOM) in Men With Prostate Cancer Undergoing Treatment With Radical Prostatectomy

Background:
- Some men with prostate cancer have their prostate glands removed. The cancer can still come back. Researchers want to know if receiving a vaccine before prostate removal surgery can lead to less recurrence.
Objective:
- To see if a vaccine and booster shots given to men with prostate cancer before surgery changes the immune cells in the prostate gland.
Eligibility:
- Men age 18 and older who have prostate cancer that has not spread, and who want to have their prostate glands removed as treatment.
Design:
Participants will be screened by their regular cancer care. They may have a small piece of prostate removed.
Participants must practice effective birth control before and during the study treatment and for 1 month after the last vaccine booster.
Participants will have a medical history, physical exam, and blood and liver tests. They will be asked about how they perform daily activities.
Participants will have a magnetic resonance imaging (MRI) scan of the prostate. The scanner is a metal cylinder in a strong magnetic field. Participants will lie on a table that slides in and out of the scanner.
Participants will be injected with the vaccine, most likely in the leg. They will be injected with the vaccine booster 3 times over several weeks.
At each booster visit, participants will have a medical history, physical exam, and blood and liver tests.
Participants will have another MRI. Then they will have surgery to remove their prostate.
Participants will have 2 follow-up visits during the year after surgery. They will have a medical history, physical exam, and blood test.

Start Date31 May 2014

Sponsor / Collaborator

National Cancer Institute

NCT00450619

/ CompletedPhase 2IIT

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

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.

Start Date01 Feb 2007

Sponsor / Collaborator

National Cancer Institute

NCT00087373

/ TerminatedPhase 2IIT

Phase II Study of Intratumoral Injection of rF-TRICOMTM in Patients With Metastatic Melanoma Who Have Detectable Tumor Associated T Cells

Vaccines may make the body build an immune response to kill tumor cells. Injecting a vaccine directly into a tumor may cause a stronger immune response and kill more tumor cells. This phase II trial is studying how well vaccine therapy works in treating patients with metastatic melanoma.

Start Date01 Jun 2004

Sponsor / Collaborator

National Cancer Institute

100 Clinical Results associated with Recombinant fowlpox-TRICOM vaccine(NCI)

100 Translational Medicine associated with Recombinant fowlpox-TRICOM vaccine(NCI)

100 Patents (Medical) associated with Recombinant fowlpox-TRICOM vaccine(NCI)

Literatures (Medical) associated with Recombinant fowlpox-TRICOM vaccine(NCI)

01 May 2014·Human Gene TherapyQ2 · MEDICINE

Results of a Randomized Phase I Gene Therapy Clinical Trial of Nononcolytic Fowlpox Viruses Encoding T Cell Costimulatory Molecules

Q2 · MEDICINE

Article

Author: Kim-Schulze, Seunghee ; Jagoda, Michael C. ; Kaufman, Howard L. ; Broucek, Joseph R. ; Kim, Dae Won ; Zloza, Andrew ; DeRaffele, Gail

Oncolytic viruses have shown promise as gene delivery vehicles in the treatment of cancer; however, their efficacy may be inhibited by the induction of anti-viral antibody titers. Fowlpox virus is a nonreplicating and nononcolytic vector that has been associated with lesser humoral but greater cell-mediated immunity in animal tumor models. To test whether fowlpox virus gene therapy is safe and can elicit immune responses in patients with cancer, we conducted a randomized phase I clinical trial of two recombinant fowlpox viruses encoding human B7.1 or a triad of costimulatory molecules (B7.1, ICAM-1, and LFA-3; TRICOM). Twelve patients (10 with melanoma and 2 with colon adenocarcinoma) enrolled in the trial and were randomized to rF-B7.1 or rF-TRICOM administered in a dose escalation manner (~3.7×10(7) or ~3.7×10(8) plaque-forming units) by intralesional injection every 4 weeks. The therapy was well tolerated, with only four patients experiencing grade 1 fever or injection site pain, and there were no serious adverse events. All patients developed anti-viral antibody titers after vector delivery, and posttreatment anti-carcinoembryonic antigen antibody titers were detected in the two patients with colon cancer. All patients developed CD8(+) T cell responses against fowlpox virus, but few responses against defined tumor-associated antigens were observed. This is the first clinical trial of direct (intratumoral) gene therapy with a nononcolytic fowlpox virus. Treatment was well tolerated in patients with metastatic cancer; all subjects exhibited anti-viral antibody responses, but limited tumor-specific T cell responses were detected. Nononcolytic fowlpox viruses are safe and induce limited T cell responses in patients with cancer. Further development may include prime-boost strategies using oncolytic viruses for initial priming.

15 Mar 2007·Clinical Cancer ResearchQ1 · MEDICINE

Combination Therapy of an Orthotopic Renal Cell Carcinoma Model Using Intratumoral Vector-Mediated Costimulation and Systemic Interleukin-2

Q1 · MEDICINE

Article

Author: Hodge, James W. ; Wiltrout, Robert ; Kudo-Saito, Chie ; Gruys, M. Eilene ; Wansley, Elizabeth K. ; Schlom, Jeffrey

AbstractPurpose: Interleukin (IL)-2 therapy is currently used for therapy of renal cell carcinoma (RCC). However, it is only effective in approximately 10% to 15% of patients, showing a need for additional therapies. We have previously described a replication-defective fowlpox vector encoding three costimulatory molecules (B7-1, ICAM-1, and LFA-3), designated rF-TRICOM. Here, we show that intratumoral administration of rF-TRICOM in an orthotopic RCC model effectively enhances tumor immunogenicity and reduces tumor burden in mice and the combination of rF-TRICOM and IL-2 is more effective than either therapy alone.Experimental Design: RCC cells were implanted under the capsule of the kidney, and mice were given rF-TRICOM intratumorally 14 days later. We compared the effect of rF-TRICOM, rF-granulocyte macrophage colony-stimulating factor (GM-CSF), and two doses of IL-2 and combinations of the above on antitumor efficacy and survival. Host CD4+ and CD8+ T-cell responses were also evaluated.Results: The results show that (a) systemic IL-2 therapy was moderately effective in the reduction of tumor burden in an orthotopic RCC model; (b) a single intratumoral injection of rF-TRICOM and rF-GM-CSF significantly reduced tumor burden; (c) the addition of systemic IL-2 to intratumoral rF-TRICOM/rF-GM-CSF administration resulted in further reduction of tumor burden, decrease in the incidence of metastasis, and extended survival in tumor-bearing mice above that seen with either treatment alone; and (d) CD8+ T cells played a critical role in the antitumor effect seen with rF-TRICOM/rF-GM-CSF + IL-2 therapy. Finally, the addition of systemic recombinant IL-15 or intratumoral vector-delivered IL-15 to intratumoral rF-TRICOM/rF-GM-CSF administration resulted in substantially more tumor-free mice than either therapy alone.Conclusions: These studies show that intratumoral administration of rF-TRICOM admixed with rF-GM-CSF is effective at reducing tumor burden in mice and the addition of IL-2 further contributes to this effect. These studies thus form the rationale for combination immunotherapy clinical trials in patients with RCC.

01 Aug 2005·Clinical Cancer ResearchQ1 · MEDICINE

Induction of Higher-Avidity Human CTLs by Vector-Mediated Enhanced Costimulation of Antigen-Presenting Cells

Q1 · MEDICINE

Article

Author: Schlom, Jeffrey ; Yang, Sixun ; Tsang, Kwong-Yok

AbstractThe efficacy of antigen-specific CD8+ CTLs depends not only on the quantity of CTLs generated but also perhaps, more importantly, on the avidity of the CTLs. To date, however, no strategy has been shown to preferentially induce higher-avidity human CTLs. In the present study, antigen-presenting cells (APC) generated from human peripheral blood mononuclear cells were infected with a recombinant avipox vector (rF-) containing the transgenes for a triad of costimulatory molecules (human B7.1, intercellular adhesion molecule-1, and LFA-3, designated as rF-TRICOM) and then used to elicit peptide-specific CTLs from autologous T cells. Compared with peptide-pulsed noninfected APCs or peptide-pulsed APCs infected with wild-type vector, peptide-pulsed APCs infected with rF-TRICOM induced not only more CTLs but also higher-avidity CTLs; this was shown by tetramer staining, tetramer dissociation, IFN-γ production, and cytolytic assays. Peptide-pulsed rF-TRICOM-infected dendritic cells were also shown to induce CTLs with a >10-fold higher avidity than CTLs induced using CD40L-matured dendritic cells; the use of peptide-pulsed CD40L-matured dendritic cells infected with rF-TRICOM as APCs induced CTLs of even greater avidity. To our knowledge, these studies are the first to show a methodology to induce higher-avidity human CTLs and have implications for the development of more efficient vaccines for a range of human cancers.

100 Deals associated with Recombinant fowlpox-TRICOM vaccine(NCI)

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Castration-Resistant Prostatic Cancer	Phase 2	United States	National Cancer Institute	01 Feb 2007
Malignant melanoma stage IV	Phase 2	United States	National Cancer Institute	01 Jun 2004
Melanoma recurrent	Phase 2	United States	National Cancer Institute	01 Jun 2004
Metastatic melanoma	Phase 2	United States	National Cancer Institute	01 Jun 2004
Bladder Squamous Cell Carcinoma	Phase 2	United States	National Cancer Institute	01 Oct 2003
Recurrent Bladder Cancer	Phase 2	United States	National Cancer Institute	01 Oct 2003
Urothelial Carcinoma of the Urinary Bladder	Phase 2	United States	National Cancer Institute	01 Oct 2003
Metastatic Solid Tumor	Phase 2	United States	National Cancer Institute	01 Dec 2001
Neoplasm Metastasis	Phase 2	United States	National Cancer Institute	01 Dec 2001

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02153918 (CTgov)	Phase 2	Castration-Resistant Prostatic Cancer	27	PROSTVAC-F/TRICOM	urimcjbiad(ogurfmhvwd) = xcsrtsvepm cjisdphgcc (aqaosdalth, lfedzawbhk - hqfultpvmw) View more	-	12 Oct 2018
NCT00450619 (CTgov)	Phase 2	Castration-Resistant Prostatic Cancer	44	Samarium Sm 153 lexidronam pentasodium+Recombinant fowlpox-TRICOM vaccine+Recombinant vaccinia-TRICOM vaccine+Sargramostim	cjrezantxz(gjizdhcfha) = afacraljqf yjkbpizimy (pprhrlsjbe, uuqxtmqruv - tbhmzyvsni) View more	-	01 Jul 2013
ASCO2004	Phase 1	Prostatic Cancer	15	recombinant Fowlpox-PSA (L155)-TRICOM (rF) (rF alone)	cjzqicsfzy(vxaebilbnu) = zxqxstjlps taajiizkjf (kpvjpztuxf ) View more	-	15 Jul 2004
ASCO2004	Phase 1	Prostatic Cancer	15	recombinant Fowlpox-PSA (L155)-TRICOM (rF) (rV followed by rF)	cjzqicsfzy(vxaebilbnu) = lgioxwrjce taajiizkjf (kpvjpztuxf ) View more	-	15 Jul 2004

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