PROSTVAC in Combination With Nivolumab in Men With Prostate Cancer
Phase I/II Study of PROSTVAC in Combination With Nivolumab in Men With Prostate Cancer
2 other identifiers
interventional
24
1 country
1
Brief Summary
Background: The immune system is the cells and organs in the body that recognize and fight infection and cancer. The prostate specific antigen (PSA)/TRICOM (PROSTVAC) vaccine might teach the immune system to find and kill certain prostate cancer cells. Nivolumab is a drug that allows the immune system to fight tumors. It might help PROSTVAC work better. Objective: To test the safety and effectiveness of the combination of PROSTVAC and nivolumab. To test this for people with castration resistant prostate cancer and then for other people with localized prostate cancer who are candidates for surgical removal of the prostate. Eligibility: Men ages 18 and older with prostate cancer Design: Participants will be screened with: Medical history Physical exam Blood and urine tests Electrocardiogram Bone scan Computed tomography (CT) scan or magnetic resonance imaging (MRI) Tumor sample. This may be from a previous procedure. All participants will get a combination of the study drugs over 8 weeks. They will have 1 visit for the initial injection then 3 booster injection / nivolumab infusion visits. Blood will be tested at these visits. Over the next 4 weeks, some participants will have: An exam of the large intestine through the rectum. CT and bone scans Standard hormonal treatment Option to continue treatment every 3 weeks if their disease does not get worse. They will have scans every 12 weeks. Other participants will have surgery to remove the prostate in week 9. Participants will have a safety visit about a month after their last treatment. This will include a physical exam, blood tests, and possibly scans. If their cancer progresses, participants will leave the study and may enroll in a long-term follow-up study. They will be contacted once a year to ask about their cancer and treatment.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1 prostate-cancer
Started Apr 2017
Longer than P75 for phase_1 prostate-cancer
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 13, 2016
CompletedFirst Posted
Study publicly available on registry
October 14, 2016
CompletedStudy Start
First participant enrolled
April 18, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 20, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2023
CompletedResults Posted
Study results publicly available
May 31, 2024
CompletedMay 31, 2024
May 1, 2024
6.2 years
October 13, 2016
April 25, 2024
May 29, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Number of Participants With Clinically Important Immune-related Adverse Events (for the Lead-In Cohort)
Clinically important immune-related adverse events were defined as grade 3 or above inflammation requiring steroids or anti cytokine therapy or not resolving to grade 1 or less within 28 days. These immune-related adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). Grade 3 is severe, grade 4 is life-threatening, and grade 5 is death related to adverse event.
From treatment start throughout study completion, an average of 1.4 years.
Changes in T-cell Infiltration in the Tumor After Neoadjuvant Treatment (Only for the Neoadjuvant Cohort)
Changes in T-cell infiltration in the tumor after neoadjuvant treatment with PROSTVAC and nivolumab, is defined as difference in density of cytotoxic T lymphocytes (CD8 T) cells and clusters of differentiation 4 (CD4 T) cells infiltrate from baseline to post-treatment (radical prostatectomy performed at week 9), calculated utilizing computer automated staining analysis. The analysis was done per tissue compartment (normal region, intra-tumoral and invasive margin). We hypothesized an increase in T cell infiltration after treatment. Statistically significant changes in T-cell infiltration are those with p\<0.05; to 0.05. The changes are not statistically significant.
From baseline to radical prostatectomy (approximately week 9)
Secondary Outcomes (14)
Number of Participants With Clinically Important Immune-related Adverse Events (Only for Neoadjuvant Cohort)
From baseline throughout study completion, an average of 20 weeks.
Changes in Soluble Immune Mediating Factors (Soluble Cluster of Differentiation 27 (sCD27) in Sera
Week 4, week 10, and week 20 after therapy compared to baseline
Changes in Soluble Immune Mediating Factors (Tumor Necrosis Factor Alpha (TNFα) and Interleukin 10 (IL-10) in Sera
Week 4, week 10, and week 20 after therapy compared to baseline
Percent Change of Tumor Cells Expressing Programmed Death-ligand 1 (PDL-1) (for the Neo-adjuvant Cohort)
Baseline (biopsy before first PROSTVAC administration) and at time of radical prostatectomy (on week 9)
Changes in Immune Cell Subsets in the Peripheral Blood
Week 4 and week 10 after therapy compared to baseline.
- +9 more secondary outcomes
Other Outcomes (1)
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)
First study intervention, Study Day 1, to 30 days after participant received last study drug administration. Approximately 1.4 years for the metastatic castration-resistant prostate cancer cohort, and an average of 20 weeks for the neoadjuvant cohort.
Study Arms (2)
Lead-in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Cohort
EXPERIMENTALProstate-specific antigen (PSA)-TRICOM vaccinia (PROSTVAC)-V on week 0 followed by booster injection called PROSTVAC-F on week 2, 4, and 8. Nivolumab will be administered on week 2, 4, 6, 8 and 10. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Participants will undergo restaging scans on week 12. If no progressive disease (PD), option to continue treatment with nivolumab every 2 weeks and PROSTVAC-F every 4 weeks until intolerance or progression. Option to extend nivolumab interval to 4 weeks for participants who remain on protocol beyond 1 year.
Neoadjuvant Cohort
EXPERIMENTALProstate-specific antigen (PSA)-TRICOM vaccinia (PROSTVAC)-V on week 0 followed by booster injection called PROSTVAC-fowlpox (F) on 2, 4 and 8 weeks. Nivolumab will be administered on week 2, 4, and 8. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Participants will undergo prostatectomy on week 9.
Interventions
PROSTVAC-V (vaccinia) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 2x10\^8 infectious units. PROSTVAC-F (fowlpox) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 1x10\^9 infectious units.
Nivolumab is to be administered as a flat dose over approximately 30-minutes via intravenous (IV) infusion.
Participants in the neoadjuvant cohort will undergo a radical prostatectomy in week 9. (If surgery is scheduled earlier than 9 weeks after initial dosing, the 6 and 8 week dosing may be skipped, and surgery may be done as early as week 5.)
A baseline biopsy is performed for participants in the neoadjuvant cohort that do not have a previous collection of biopsy material.
Participants who experience aches or fever after vaccination may take Tylenol as directed.
Eligibility Criteria
You may qualify if:
- For the neoadjuvant cohort, 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. For the castration-resistant prostate cancer (CRPC) lead in cohort, if histopathological documentation is unavailable, a rising prostate specific antigen (PSA) and a clinical course consistent with prostate cancer would be acceptable.
- Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of PROSTVAC in combination with nivolumab, ipilimumab or both in participants \<18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Participants must not have other active invasive malignancies within the past 2 years (with the exception, of non-melanoma skin cancers) (for CRPC cohort only).
- Participants must be willing to travel to the study site for follow-up visits
- All participants who have received prior vaccination with vaccinia virus (for smallpox immunization) must not have a history of serious adverse reaction to the vaccine.
- The effects of PROSTVAC in combination nivolumab, ipilimumab or both on the developing human fetus are unknown. For this reason, men must agree to use adequate contraception (abstinence, vasectomy) or female partner must use (intrauterine device (IUD), hormonal \[birth control, pills, injections, or implants\], tubal ligation\] prior to study entry and for up to 7 months after the last dose.
- Participants must understand and sign informed consent that explains the neoplastic nature of their disease, the procedures to be followed, the experimental nature of the treatment, alternative treatments, potential risks and toxicities, and the voluntary nature of participation.
- Participants must have normal organ and marrow function as defined below:
- hemoglobin greater than or equal to 8 g/dL
- granulocytes greater than or equal to 1,500/mcL
- platelets greater than or equal to 100,000/mcL
- total bilirubin \< 1.5 mg/dL (or less than or equal to 3.0 mg/dL in patients with Gilbert syndrome)
- Aspartate aminotransferase (AST)serum glutamic oxaloacetic transaminase (SGOT)(SGOT)/alanine transaminase (ALT)serum glutamic-pyruvic transaminase (SGPT) less than or equal to 2.5 X institutional upper limit of normal
- creatinine less than or equal to 1.5 X ULN
- +10 more criteria
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
- Participants should have no evidence, as listed below, of being immunocompromised:
- Human immunodeficiency virus (HIV) positivity due to the potential for decreased tolerance and risk for severe side effects.
- Hepatitis B or C positivity.
- Concurrent use of systemic steroids or steroid eye drops. This is to avoid immunosuppression which may lead to potential complications with vaccinia (priming vaccination). Nasal, topical, or inhaled steroid use is permitted.
- Participants with known allergy to eggs or to compounds with a similar chemical or biologic composition to PROSTVAC, ipilimumab or nivolumab.
- No prior immune checkpoint inhibitors (e.g., anti-cytotoxic T-lymphocyte associated protein 4 (CTLA4), anti-programmed cell death protein 1 (PD-1) or anti-programmed death-ligand 1 (PDL1) are allowed.
- Other serious intercurrent illness.
- Participants 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.
- Participants with significant autoimmune disease that is active or potentially life threatening if activated.
- Participants with clinically significant cardiomyopathy requiring treatment.
- +11 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Related Publications (1)
Lassoued W, Madan RA, Xue E, Burnett D, Canubas KD, Bailey S, Marte JL, Tsai YT, Donahue RN, Turkbey IB, Papanicolau-Sengo A, Williams M, Hankin A, Manukyan M, Manu M, Kang Z, Pritchard C, Dahut W, Karzai F, Schlom J, Sater S, Pinto P, Gulley JL. Programmed death-1 inhibition increases vaccine-induced T-cell infiltration in patients with prostate cancer. J Immunother Cancer. 2025 Jun 22;13(6):e010851. doi: 10.1136/jitc-2024-010851.
PMID: 40550568DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. James L. Gulley
- Organization
- National Cancer Institute
Study Officials
- PRINCIPAL INVESTIGATOR
James L Gulley, M.D.
National Cancer Institute (NCI)
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
October 13, 2016
First Posted
October 14, 2016
Study Start
April 18, 2017
Primary Completion
June 20, 2023
Study Completion
December 1, 2023
Last Updated
May 31, 2024
Results First Posted
May 31, 2024
Record last verified: 2024-05
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol Genomic Data Sharing (GDS) plan for as long as database is active.
- Access Criteria
- Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI). Genomic data are made available via the database of Genotypes and Phenotypes (dbGaP) through requests to the data custodians.
All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request. All IPD recorded in the medical record will be shared with intramural investigators upon request. In addition, all large-scale genomic sequencing data will be shared with subscribers to the database of Genotypes and Phenotypes (dbGaP).