Vaccine Plus Booster Shots in Men With Prostate Cancer Undergoing Treatment With Radical Prostatectomy

NCT02153918 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 14011214-C-0112
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Prostate Cancer; Prostatic Neoplasms; Neoplasms, Prostate

Keywords

Surgery; Neoadjuvant; CD8 Cell Infiltrate Response; CD4 Cell Infiltrate Response; Vaccine

Outcome Measures

Primary Outcomes (1)

• Changes From Baseline to After Surgery of Cluster of Differentiation 4 (CD4) and Cluster of Differentiation 8 (CD8) Cell Infiltrates

  Immunologic CD4 and CD8 cell infiltrate response of a neoadjuvant prime/boost vaccine strategy in prostatectomy specimens. Prostate biopsy specimens are collected and stained for CD4 and CD8 cells. Quantification is reported as the number of stained cells per micron squared of surface area. Change will be noted by utilizing computer automated staining analysis. Density of cell infiltrate will be calculated and the pre and post vaccine values will be compared to determine response to vaccine.

  Baseline (pre vaccination) and approximately week 10

Secondary Outcomes (5)

• Count of Participants With Change in Peripheral Prostatic Specific Antigen (PSA)-Specific T Cell Responses

  Baseline (pre vaccination) and week 10

• Intraprostatic Treg Cell Infiltration With Cluster of Differentiation 4 (CD4)+Forkhead Box P3 (FOX-P3) Staining

  Baseline (pre vaccination) and post surgery after last dose of vaccine, approximately week 10

• Prostatic Specific Antigen (PSA) Changes Secondary to Vaccination

  Baseline (pre vaccination) and approximately week 10

• Magnetic Resonance Imaging (MRI) Changes Secondary to Vaccination

  Baseline (pre vaccination) and approximately week 10

• Count of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)

  Date treatment consent signed to date off study, approximately 33 months and 5 days

Study Arms (1)

Vaccine Plus Booster Shots

EXPERIMENTAL

PROSTVAC-V/TRICOM followed by PROSTVAC-F/ TRICOM boost monthly until radical prostatectomy or off therapy PROSTVAC

Biological: PROSTVAC-V/TRICOM; Biological: PROSTVAC-F/TRICOM

Interventions

PROSTVAC-V/TRICOM BIOLOGICAL

A recombinant vaccinia virus vector vaccine containing the genes for human prostatic specific antigen (PSA) and three co-stimulatory molecules.

Vaccine Plus Booster Shots

PROSTVAC-F/TRICOM BIOLOGICAL

A recombinant fowlpox virus vector vaccine containing the genes for human PSA and three co-stimulatory molecules.

Vaccine Plus Booster Shots

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histopathological documentation of adenocarcinoma of the prostate prior to starting this study and evaluable biopsy tissue (e.g., unstained slides or blocks) available for analysis. If evaluable tissue is not available, the patient must agree to undergo a pre-vaccination prostate biopsy on study as an alternative to having available tissue available.
• Patients must be a surgical candidate for radical prostatectomy based on standard workup of prostatic specific antigen (PSA), biopsy results, and if necessary supplemental imaging.
• Patients must have chosen radical prostatectomy as their definitive treatment of choice for management of their prostate cancer.
• Patients must have a performance status of 0 to 1 according to the Eastern Cooperative Oncology Group (ECOG) criteria
• No systemic steroid or steroid eye drop use within 2 weeks prior to initiation of experimental therapy. Limited doses of systemic steroids to prevent intravenous (IV) contrast, allergic reaction or anaphylaxis (in patients who have known contrast allergies) are allowed.
• Hematological eligibility parameters (within one month of starting therapy):
• Granulocyte count greater than or equal to 1,500/mm(3)
• Platelet count greater than or equal to 50,000/mm(3)
• Hemoglobin (Hgb) greater than or equal to 8 g/dL
• Biochemical eligibility parameters (within one month of starting therapy):
• Hepatic function: Bilirubin \< 1.5 mg/dl (OR in patients with Gilbert's syndrome, a total bilirubin less than or equal to 3.0 mg/dL), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 2.5 times upper limit of normal.-. Creatinine less than or equal to 1.5 X ULN
• Creatinine less than or equal to 1.5 X ULN
• Patients must be test negative for human immunodeficiency virus (HIV), Hepatitis B and C.
• Patients must not have other active invasive malignancies within the past 2 years (with the exception of non-melanoma skin cancers) or life threatening illnesses.
• Patients must be willing to travel to the study site for follow-up visits.

You may not qualify if:

• Prior splenectomy.
• The recombinant vaccinia vaccine should not be administered if the following apply to either recipients or, for at least 3 weeks after vaccination, their close household contacts (Close household contacts are those who share housing or have close physical contact):
• Persons with active or a history of eczema or other eczematoid skin disorders
• Those with other acute, chronic or exfoliative skin conditions (e.g., atopic dermatitis, burns, impetigo, varicella zoster, severe acne or other open rashes or wounds) until condition resolves
• Pregnant or nursing women; children under 3 years of age
• Patients should have no evidence, as listed below, of being immunocompromised:
• 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.
• Patients with known allergy to eggs.
• Other serious intercurrent illness.
• Patients with a history of unstable or newly diagnosed angina pectoris, recent myocardial infarction (within 6 months of enrollment) or New York Heart Association class II-IV congestive heart failure.
• Patients with significant autoimmune disease that is active or potentially life threatening if activated.
• Patients with clinically significant cardiomyopathy requiring treatment.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• DiPaola RS, Plante M, Kaufman H, Petrylak DP, Israeli R, Lattime E, Manson K, Schuetz T. A phase I trial of pox PSA vaccines (PROSTVAC-VF) with B7-1, ICAM-1, and LFA-3 co-stimulatory molecules (TRICOM) in patients with prostate cancer. J Transl Med. 2006 Jan 3;4:1. doi: 10.1186/1479-5876-4-1.

  PMID: 16390546 BACKGROUND

• Gulley JL, Heery CR, Madan RA, Walter BA, Merino MJ, Dahut WL, Tsang KY, Schlom J, Pinto PA. Phase I study of intraprostatic vaccine administration in men with locally recurrent or progressive prostate cancer. Cancer Immunol Immunother. 2013 Sep;62(9):1521-31. doi: 10.1007/s00262-013-1448-0. Epub 2013 Jul 9.

  PMID: 23836412 BACKGROUND

• Kantoff PW, Schuetz TJ, Blumenstein BA, Glode LM, Bilhartz DL, Wyand M, Manson K, Panicali DL, Laus R, Schlom J, Dahut WL, Arlen PM, Gulley JL, Godfrey WR. Overall survival analysis of a phase II randomized controlled trial of a Poxviral-based PSA-targeted immunotherapy in metastatic castration-resistant prostate cancer. J Clin Oncol. 2010 Mar 1;28(7):1099-105. doi: 10.1200/JCO.2009.25.0597. Epub 2010 Jan 25.

  PMID: 20100959 BACKGROUND

• Abdul Sater H, Marte JL, Donahue RN, Walter-Rodriguez B, Heery CR, Steinberg SM, Cordes LM, Chun G, Karzai F, Bilusic M, Harmon SA, Turkbey IB, Choyke PL, Schlom J, Dahut WL, Madan RA, Pinto PA, Gulley JL. Neoadjuvant PROSTVAC prior to radical prostatectomy enhances T-cell infiltration into the tumor immune microenvironment in men with prostate cancer. J Immunother Cancer. 2020 Mar;8(1):e000655. doi: 10.1136/jitc-2020-000655.

  PMID: 32269146 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Prostatic Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Dr. Peter Pinto
• Organization: National Cancer Institute

pintop@nih.gov

301-496-6353

Study Officials

• Peter A Pinto, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 31, 2014
• First Posted: June 3, 2014
• Study Start: May 31, 2014
• Primary Completion: July 28, 2017
• Study Completion: January 16, 2018
• Last Updated: October 12, 2018
• Results First Posted: October 12, 2018

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)