Prostatic NeoplasmsPhase 2NCT02506114
Neoadjuvant PROSTVAC-VF With or Without Ipilimumab for Prostate Cancer
A Phase 2 study testing PROSTVAC V/F and Ipilimumab in people with Prostatic Neoplasms, run by Lawrence Fong at 1 site in United States.
Trial summary
This is a multicentered, open label, randomized phase II trial of PROSTVAC or ipilimumab or the combination of PROSTVAC and ipilimumab as neoadjuvant therapy in patients with localized prostate cancer. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostatic Neoplasms
- What is being tested?
- PROSTVAC V/F and Ipilimumab
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Oct 2016to 22 Apr 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- For a subject to be eligible for participation in this study, all of the following criteria must be satisfied:
- Patients must have histologically confirmed adenocarcinoma of the prostate without previous therapy for prostate cancer (PC).
- Treatment-naïve AND
- Undergoing radical prostatectomy (RP) as initial, locally definitive therapy for PC and
- Eligible for RP in a 3 month timeframe AND
- Consentable for RP
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- Subject's archival prostate biopsy specimen is available, and subject consents to provide tissue for study endpoint analysis. The prostate biopsy slides or blocks must be available prior to starting any study treatment.
- Age ≥ 18 years
- Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Subject has adequate organ function, defined as:
- White blood cell (WBC) count ≥ 3,000/microliter (mcL)
- Absolute neutrophil count (ANC) ≥ 1,500/mcL
- Platelet count ≥ 100,000/mcL
- Hemoglobin (Hgb) ≥ 10.0 g/dL
- Creatinine ≤ 1.5x institutional upper limit of normal (ULN)
- Total bilirubin ≤ 1.5 x institutional ULN
- Alanine aminotransferase (ALT) ≤ 1.5 x institutional ULN
- Aspartate aminotransferase (AST) ≤ 1.5 x institutional ULN
- Prothrombin time (PT) /International Normalized Ratio (INR), partial thromboplastin time (PTT) within institutional ULN
- No known history of human immunodeficiency virus (HIV) 1 and 2, human T-cell lymphotropic virus (HTLV)-I/II, and Hepatitis B and C.
- Ability to understand a written informed consent document, and the willingness to sign it.
- Because of the unknown potential risk to a gamete and/or developing embryo from these investigational therapies, subjects must agree to use adequate contraception (i.e. barrier method) for the duration of study participation, and for three months after discontinuing therapy.
Who cannot join
- A subject will not be eligible for participation in this study if any of the following criteria apply.
- Subject's biopsy specimen reveals neuroendocrine or small cell features.
- Subject has any evidence of metastatic disease (pre-operative staging will be undertaken per urologic standard of care) as deemed by the Investigator.
- Subject has prior use of any hormones, including luteinizing hormone-releasing hormone (LHRH) agonists, ketoconazole, antiandrogens (such as bicalutamide, flutamide, or nilutamide), or 5-α-reductase inhibitors.
- Subject has prior use of any anti-cancer treatment or product, such as PC-SPES (or any other PC-x product: PC-HOPE, PC-CARE, PC-PLUS, etc).
- Subject has received prior radiation therapy or chemotherapy for prostate cancer.
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- Chronic administration (defined as daily or every other day for continuous use >14 days) of systemic corticosteroids within 28 days of the first planned dose off PROSTVAC-V/F. Use of inhaled steroids, nasal sprays, and topical creams for small body areas are allowed.
- Active atopic dermatitis or skin condition that disrupts the epidermis
- Inflammatory eye disease requiring steroid treatment
- History of prior solid organ or bone marrow transplant
- Previous history of hypersensitivity to eggs or allergy or untoward reaction to prior vaccinia (smallpox) vaccination.
- Splenectomy
- Subject, or subject's close household contacts (defined as those who share housing or have close physical contact) have any of the following conditions during the screening and/or treatment periods:
- active or a history of atopic dermatitis, eczema or other eczematoid skin disorders that disrupt the epidermis
- other acute, chronic or exfoliative skin conditions (e.g., burns, impetigo, varicella zoster, severe acne or other open rashes or wounds) until condition resolves
- pregnant or nursing
- immunodeficient or immunosuppressed (by disease or therapy), including HIV infection
- Subject's close household contacts include children less than the age of three
- History of, or active autoimmune disease (e.g., autoimmune neutropenia, thrombocytopenia, or hemolytic anemia, systemic lupus erythematosis, Sjogren´s syndrome, scleroderma, myasthenia gravis, Goodpasture´s syndrome, Addison´s disease, Hashimotos´s thyroiditis, or Graves disease) as determined by the treating medical oncologist.
- Persons with vitiligo are not excluded.
- Diabetics are not excluded if the condition is well controlled:
- Hemoglobin A1C < 7.0, and
- No evidence of end-organ damage due to diabetes, such as diabetic retinopathy, nephropathy, or neuropathy
- Persons with type 2 diabetes are not excluded since this is not an autoimmune disease, and do not need to meet these criteria.
- Persons with hypothyroidism are not excluded if condition is well controlled, and condition is due to a non-autoimmune etiology.
- Subject has received treatment with any investigational immunotherapy within 2 years prior to study screening or has received treatment with any other investigational product within 28 days prior to study screening.
- Subject has participated in any previous study involving PROSTVAC-V/F, Sipuleucel-T or ipilimumab, regardless of whether the subject received PROSTVAC-V/F, Sipuleucel-T or ipilimumab.
- Subject has a history of allergic reactions attributed to compounds of similar chemical or biologic composition to PROSTVAC-V/F or ipilimumab.
- Subject has a history of stage III or greater cancer, excluding prostate cancer. Subjects with a history of basal or squamous cell skin cancers are allowed, provided that the subject was adequately treated and is disease-free at the time of study screening. Subjects with a history of stage I or II cancer must have been adequately treated and been disease-free for ≥ 3 years prior to study screening.
- Subject has any uncontrolled, concurrent illness including, but not limited to the following: ongoing or active infection (bacterial, viral, or fungal), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, stroke or myocardial infarction within 6 months, or psychiatric illness that would limit compliance with study requirements.
- Subject requires any medical intervention(s) or has any other condition(s) that, in the Investigator's opinion, will 1) make the administration of PROSTVAC or ipilimumab hazardous, 2) obscure the interpretation of adverse events (AEs), 3) compromise adherence with study requirements, or 4) otherwise compromise the study's objectives.
- Subject has high-risk features (e.g., based on Gleason score, PSA, clinical stage, % positive biopsies), and the treating physician feels the subject should undergo radical prostatectomy sooner than planned within the protocol.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, San Francisco
San Francisco, California, 94143
About this study
Official title: An Open Label, Randomized Phase 2 Trial of Prostvac and Ipilimumab as Monotherapy or in Combination for Men With Localized Prostate Cancer Undergoing Radical Prostatectomy
This is a multicentered, open label, randomized phase II trial of PROSTVAC or ipilimumab or the combination of PROSTVAC and ipilimumab as neoadjuvant therapy in patients with localized prostate cancer. Eligible patients will be randomized to PROSTVAC monotherapy (Arm A), ipilimumab monotherapy (Arm B), or combination therapy with both PROSTVAC and ipilimumab (Arm C), prior to RP. In arms A and C, PROSTVAC-V will be administered subcutaneously as the primary vaccine on Day 1, which will be followed 2 weeks later with a series of 2 PROSTVAC-F subcutaneous administrations, given 3 weeks apart. In arms B and C, ipilimumab will be administered twice, at a dose of 3mg/kg, 3 weeks apart. In the combination arm, ipilimumab administration will coincide with the PROSTVAC-F administration. In arm B, ipilimumab will begin on Day 1. In all three arms, radical prostatectomy (RP) will occur 21 days, or three weeks, following final treatment administration of PROSTVAC or ipilimumab. No further therapy will be administered on study following RP.
- Conditions
- Prostatic Neoplasms
- Being tested
- PROSTVAC V/F, Ipilimumab
- Keywords
- prostate
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PROSTVAC V/FBiological
PROSTVAC-V/F is a prostate-specific antigen(PSA)-based immunization strategy. It is intended to generate immune responses to prostate specific antigens and prostate cancer cells. It uses poxviral vectors to introduce modified PSA to the patient in an immunogenic manner to break self-tolerance, and thereby induce immune responses directed against prostate cancer cells.
IpilimumabDrug
| Study group | Role | What they receive |
|---|---|---|
| Arm A: PROSTVAC-V/F | Experimental | PROSTVAC-V: 2 x 10^8pfu; subcutaneous; Day 1. PROSTVAC-F: 1 x 10^9pfu; subcutaneous; Days 15, and 36. Receives: Biological: PROSTVAC V/F |
| Arm B: Ipilimumab Monotherapy | Experimental | Ipilimumab: 3 mg/kg; intravenously; Days 1 and 21. Receives: Drug: Ipilimumab |
| Arm C: Combined PROSTVAC-V/F + Ipilimumab | Experimental | PROSTVAC-V: 2 x 10^8pfu; subcutaneous; Day 1. PROSTVAC-F: 1 x 10^9pfu; subcutaneous; Days 15, and 36. Ipilimumab: 3 mg/kg; intravenously; Days 15 and 36. Receives: Biological: PROSTVAC V/F; Drug: Ipilimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of Participants With Positive CD3+ T Cell Immune Response
The proportion of participants who demonstrated a positive response following neoadjuvant therapy as measured by change from baseline in CD3+ T cell infiltration within prostate tumor tissue by immunohistochemistry (IHC) assessment following treatment will be reported. The change in the number of CD3+ T cell infiltration within prostate tissue between the biopsy and radical prostatectomy (RP) specimen will be quantified using immunohistochemistry (IHC),with a positive result if there is >=2 fold increase in the number of CD3+T cell infiltration.
Measured: Up to 2 years
Secondary outcomes (4)
Proportion of Participants With Any Positive Change in Immunologic Infiltration (CD3)
The proportion of participants who demonstrated any change in the number of infiltrating T cells/μm2 of CD3 within the prostatic tumor tissue from the diagnostic core biopsy specimens to the post treatment prostatectomy tissue specimens will be assessed, based upon IHC analysis following neoadjuvant PROSTVAC, ipilimumab, or the combination of the two treatments.
Measured: Up to 2 years
Proportion of Participants With Any Positive Change in Circulating Effector T Cells
The proportion of participants who demonstrated any change in the number of circulating effector T cells/μm2 within the prostatic tumor tissue from the diagnostic core biopsy specimens to the post treatment prostatectomy tissue specimens will be assessed, based upon IHC analysis following neoadjuvant PROSTVAC, ipilimumab, or the combination by flow cytometry assessment of peripheral blood mononuclear cells
Measured: Up to 2 years
Proportion of Participants With a Positive Change in Regulatory T Cells
The proportion of participants who demonstrated a change in the number of Regulatory T Cells/μm2 within the prostatic tumor tissue from the diagnostic core biopsy specimens to the post treatment prostatectomy tissue specimens will be assessed, based upon IHC analysis following neoadjuvant PROSTVAC, ipilimumab, or the combination by flow cytometry assessment of peripheral blood mononuclear cells
Measured: Up to 2 years
Number of Participants With Treatment-Related Adverse Events
Safety analyses will be performed for all participants having received at least one dose of study drug. The investigator will use the NCI Common Terminology Criteria for Adverse Events (CTCAE) v.4.03 for reporting the number of participants with treatment-related, non-hematologic, adverse events and modified criteria for hematologic adverse events defined as having an attribute of possible, probable, or definite by toxicity and treatment group.
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2015 (estimated)
- Study start6 Oct 2016
- Primary completion22 Apr 2020
- Study completion22 Apr 2020
Why it stopped: Low Accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Prostatic NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lawrence Fong
- Sponsor type
- University, hospital or other
- Collaborators
- Bavarian Nordic
- Responsible party
- Sponsor-investigator, Lawrence Fong, University of California, San Francisco
- Investigators
- Lawrence Fong, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02506114
- Sponsor's protocol ID
- 14559
- Other IDs
- NCI-2017-01679
- Status last verified
- Oct 2021
- First submitted
- 21 Jul 2015
- Last updated
- 24 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label, Randomized Phase 2 Trial of Prostvac and Ipilimumab as Monotherapy or in Combination for Men With Localized Prostate Cancer Undergoing Radical Prostatectomy
- ClinicalTrials.gov ID
- NCT02506114
- Acronym / sponsor ID
- 14559
- Conditions
- Prostatic Neoplasms
- Keywords
- prostate
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low Accrual
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Lawrence FongUniversity, hospital or other
- Collaborators
- Bavarian Nordic
- Study start
- 6 Oct 2016 (actual)
- Primary completion
- 22 Apr 2020 (actual)
- Study completion
- 22 Apr 2020 (actual)
- First posted
- 22 Jul 2015 (estimated)
- Results
- Posted 24 Nov 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a multicentered, open label, randomized phase II trial of PROSTVAC or ipilimumab or the combination of PROSTVAC and ipilimumab as neoadjuvant therapy in patients with localized prostate cancer. Eligible patients will be randomized to PROSTVAC monotherapy (Arm A), ipilimumab monotherapy (Arm B), or combination therapy with both PROSTVAC and ipilimumab (Arm C), prior to RP. In arms A and C, PROSTVAC-V will be administered subcutaneously as the primary vaccine on Day 1, which will be followed 2 weeks later with a series of 2 PROSTVAC-F subcutaneous administrations, given 3 weeks apart. In arms B and C, ipilimumab will be administered twice, at a dose of 3mg/kg, 3 weeks apart. In the combination arm, ipilimumab administration will coincide with the PROSTVAC-F administration. In arm B, ipilimumab will begin on Day 1. In all three arms, radical prostatectomy (RP) will occur 21 days, or three weeks, following final treatment administration of PROSTVAC or ipilimumab. No further therapy will be administered on study following RP.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm A: PROSTVAC-V/F | Experimental | Biological: PROSTVAC V/FPROSTVAC-V: 2 x 10^8pfu; subcutaneous; Day 1. PROSTVAC-F: 1 x 10^9pfu; subcutaneous; Days 15, and 36. |
| Arm B: Ipilimumab Monotherapy | Experimental | Drug: IpilimumabIpilimumab: 3 mg/kg; intravenously; Days 1 and 21. |
| Arm C: Combined PROSTVAC-V/F + Ipilimumab | Experimental | Biological: PROSTVAC V/F, Drug: IpilimumabPROSTVAC-V: 2 x 10^8pfu; subcutaneous; Day 1. PROSTVAC-F: 1 x 10^9pfu; subcutaneous; Days 15, and 36. Ipilimumab: 3 mg/kg; intravenously; Days 15 and 36. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- For a subject to be eligible for participation in this study, all of the following criteria must be satisfied:
- Patients must have histologically confirmed adenocarcinoma of the prostate without previous therapy for prostate cancer (PC).
- Subject's archival prostate biopsy specimen is available, and subject consents to provide tissue for study endpoint analysis. The prostate biopsy slides or blocks must be available prior to starting any study treatment.
- Age ≥ 18 years
- Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Key exclusion criteria (32 listed)
- A subject will not be eligible for participation in this study if any of the following criteria apply.
- Subject's biopsy specimen reveals neuroendocrine or small cell features.
- Subject has any evidence of metastatic disease (pre-operative staging will be undertaken per urologic standard of care) as deemed by the Investigator.
- Subject has prior use of any hormones, including luteinizing hormone-releasing hormone (LHRH) agonists, ketoconazole, antiandrogens (such as bicalutamide, flutamide, or nilutamide), or 5-α-reductase inhibitors.
- Subject has prior use of any anti-cancer treatment or product, such as PC-SPES (or any other PC-x product: PC-HOPE, PC-CARE, PC-PLUS, etc).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PROSTVAC V/FPROSTVAC-V/F is a prostate-specific antigen(PSA)-based immunization strategy. It is intended to generate immune responses to prostate specific antigens and prostate cancer cells. It uses poxviral vectors to introduce modified PSA to the patient in an immunogenic manner to break self-tolerance, and thereby induce immune responses directed against prostate cancer cells. | Biological | Arm A: PROSTVAC-V/F, Arm C: Combined PROSTVAC-V/F + Ipilimumab |
| Ipilimumab | Drug | Arm B: Ipilimumab Monotherapy, Arm C: Combined PROSTVAC-V/F + Ipilimumab |
Primary outcome
Proportion of Participants With Positive CD3+ T Cell Immune Response
Time frame: Up to 2 years
The proportion of participants who demonstrated a positive response following neoadjuvant therapy as measured by change from baseline in CD3+ T cell infiltration within prostate tumor tissue by immunohistochemistry (IHC) assessment following treatment will be reported. The change in the number of CD3+ T cell infiltration within prostate tissue between the biopsy and radical prostatectomy (RP) specimen will be quantified using immunohistochemistry (IHC),with a positive result if there is >=2 fold increase in the number of CD3+T cell infiltration.
4 secondary outcomes
Proportion of Participants With Any Positive Change in Immunologic Infiltration (CD3)
Time frame: Up to 2 years
Proportion of Participants With Any Positive Change in Circulating Effector T Cells
Time frame: Up to 2 years
Proportion of Participants With a Positive Change in Regulatory T Cells
Time frame: Up to 2 years
Number of Participants With Treatment-Related Adverse Events
Time frame: Up to 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lawrence Fong, MD principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing PROSTVAC V/F and Ipilimumab in people with Prostatic Neoplasms, run by Lawrence Fong at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 24 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Nov 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of Participants With Positive CD3+ T Cell Immune Response (time frame: Up to 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Nov 2021.