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Metastatic Hormone-Sensitive Prostate CancerPhase 1NCT03532217

Neoantigen DNA Vaccine in Combination With Nivolumab/Ipilimumab and PROSTVAC in Metastatic Hormone-Sensitive Prostate Cancer

A Phase 1 study testing PROSTVAC-V, PROSTVAC-F and Nivolumab in people with Metastatic Hormone-Sensitive Prostate Cancer, run by Washington University School of Medicine at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study study aims to elucidate the immune responses to a shared antigen vaccine (PROSTVAC) and tumor specific antigens generated DNA vaccine in combination with checkpoint blockade using nivolumab (anti-PD-1), and ipilimumab (anti-CTLA-4). Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
PROSTVAC-V, PROSTVAC-F and Nivolumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
19 participants
Where
1 siteUnited States
Study dates
14 Sep 2018to 25 Jul 2022
Phase
Phase 1
Are there results?
None posted in the registry

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

  • Histologically confirmed adenocarcinoma of the prostate.
  • High risk/volume metastatic disease, as defined by 4 or more sites of disease or the presence of visceral metastases.
  • Must have completed an adequate course of chemo-hormonal, first line therapy for metastatic hormone-sensitive prostate cancer, as determined by the investigator. Patients must remain on stable dose of ADT with castrate levels of testosterone (defined as testosterone < 50 ng/dL)
  • At least 18 years of age.
  • PSA may be undetectable after initial chemo-ADT.
  • ECOG performance status ≤ 2
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  • Normal bone marrow and organ function as defined below:
  • Leukocytes ≥ 2,000/ul
  • Absolute neutrophil count ≥ 1,500/ul
  • Platelets ≥ 100,000/ul
  • Hemoglobin ≥ 9.0 g/ul
  • Total bilirubin ≤ 1.5 x ULN (except subjects with Gilbert's syndrome who must have a total bilirubin level of ≤ 3.0 ULN)
  • AST(SGOT) ≤ 3.0 x ULN
  • ALT(SGPT) ≤ 3.0 x ULN
  • Creatinine ≤ 1.5 x ULN OR calculated creatinine clearance ≥ 40 mL/min using the Cockcroft-Gault formula
  • Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
  • Must have a biopsy of a metastatic site of disease (may be archival) available and adequate for evaluation and determination of neoantigens by genomic analyses.
  • Must have all AEs resolved to baseline prior to chemo-ADT, or if treatment related, resolved to grade 1 prior to enrollment.

Who cannot join

  • Significant small cell or neuroendocrine component or histology, as determined by the institution's reading pathologist.
  • Progression of disease as defined by a rising PSA (3 sequential values, at least 1 week apart) or radiographic progression based on RECIST1.1 or PCWG3 criteria.
  • Prior treatment with a checkpoint inhibitor, neoantigen vaccine, or PROSTVAC.
  • Participants with active, known or suspected autoimmune disease. Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment are permitted to enroll.
  • Diagnosis of atopic dermatitis or other active exfoliative skin condition
  • History of concurrent second cancers requiring active, ongoing systemic treatment
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  • Currently receiving any other investigational agents.
  • Known brain metastases. Prostate cancer patients with known brain metastases must be excluded from this clinical trial because of their poor prognosis, and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
  • A history of allergic reactions attributed to compounds of similar chemical or biologic composition to anti-PD-1, anti-CTLA-4, Prostvac-VF Tricom, DNA vaccines, or other agents used in the study.
  • Prior allergy or significant systemic reaction to vaccinia.
  • Prior reactions to monoclonal antibodies.
  • Received hematopoietic stem cell transplant < 24 months prior to enrollment to this study, or received hematopoietic stem cell transplant ≥ 24 months prior to enrollment to this study but has graft-versus-host disease or disease relapse.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, clinically significant congestive heart failure (NYHA Class III, IV), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that in the opinion of the investigator would limit compliance with study requirements.
  • Immunosuppressed status (e.g. HIV/AIDS, active HCV/HBV, high dose systemic steroids, etc.) as determined by the investigator; topical or inhaled steroids are acceptable.
  • History of syncopal or vasovagal episode as determined by medical record and history in the 12 month period prior to first vaccination administration.
  • Individuals in whom a skinfold measurement of the cutaneous and subcutaneous tissue for eligible injection sites (left and right medial deltoid region) exceeds 40 mm.
  • Individuals in whom the ability to observe possible local reactions at the eligible injection sites (deltoid region) is, in the opinion of the investigator, unacceptably obscured due to a physical condition or permanent body art.
  • Therapeutic or traumatic metal implant in the skin or muscle of either deltoid region.
  • Any chronic or active neurologic disorder, including seizures and epilepsy, excluding a single febrile seizure as a child.
  • Current use of any electronic stimulation device, such as cardiac demand pacemakers, automatic implantable cardiac defibrillator, nerve stimulators, or deep brain stimulators.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: A Pilot Trial of Neoantigen DNA Vaccine in Combination With Nivolumab/Ipilimumab and PROSTVAC in Metastatic Hormone-Sensitive Prostate Cancer

This study study aims to elucidate the immune responses to a shared antigen vaccine (PROSTVAC) and tumor specific antigens generated DNA vaccine in combination with checkpoint blockade using nivolumab (anti-PD-1), and ipilimumab (anti-CTLA-4). Additionally, the investigators will study the impact of the combination immunotherapy on peripheral T cell activation, as well as immune response in the tumor microenvironment. Finally, the investigators will evaluate the safety and tolerability to this novel personalized immunotherapy in combination with checkpoint blockade.

Being tested
PROSTVAC-V, PROSTVAC-F, Nivolumab, Ipilimumab, Neoantigen DNA vaccine

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PROSTVAC-VBiological

    -Replication-competent vaccinia virus which has been engineered to encode the sequences for a modified human prostate-specific antigen (PSA) and a triad of co-stimulatory molecules (TRICOM)

  • PROSTVAC-FBiological

    -Fowlpox virus which does not replicate in human cells and has been engineered to encode the same sequences present in PROSTVAC-V.

  • NivolumabDrug

    -Nivolumab is a human monoclonal antibody (mAb)

  • IpilimumabDrug

    -Ipilimumab is a mAb blocking the inhibitory signal mediated by cytotoxic T Lymphocyte-associated antigen 4 (CTLA-4), a protein receptor that downregulates the immune system.

  • Neoantigen DNA vaccineBiological

    Each DNA vaccination will be 1 mL vaccine administered intramuscularly. At each vaccination time point, patients will receive two injections at separate sites.

  • TriGrid Delivery SystemDevice

    Also called TDS-IM

    -Electroporation device

  • Tumor biopsyProcedure or surgery

    -Pre-treatment, post-treatment A (optional), and end of treatment

  • Peripheral bloodProcedure or surgery

    -At the time of pre-treatment biopsy, mid-treatment of chemo-ADT, at time of enrollment (prior to POSTVAC administration), mid-treatment A, mid-treatment B (multiple)

  • Fecal samplesProcedure or surgery

    -Post chemo/pre-treatment A, post-treatment A, pre-treatment B, post-treatment B

  • LeukapheresisProcedure or surgery

    • Post-treatment A/pre-treatment B
    • Mid-Treatment B, after Cycle 9 Day 1 and prior to Cycle 10 Day 1
    • End of treatment
Study groups in NCT03532217
Study groupRoleWhat they receive
PROSTVAC/Ipilimumab/Nivolumab/Neoantigen DNA vaccineExperimental* Within 60 days after the last chemo, patients will start a priming dose of PROSTVAC-V, and subsequent doses of PROSTVAC- F (weeks 0, 2, 5, 8, 11, 14, and 17). During "Treatment A" phase, subjects should receive nivolumab intravenously on Day 1 of each cycle every 3 weeks for 6 doses. Ipilimumab on Day 1 of each cycle every 3 weeks for 2 doses. * Patients will then receive a neoantigen DNA vaccine with continuous nivolumab treatment. The vaccine will be administered starting approximately week 21 by intramuscular injection for a total of 6 treatments every 28 days +/-7 days. Each DNA vaccination will be 4 mg vaccine administered intramuscularly using a TriGrid electroporation device. Patients will receive nivolumab at 480 mg every 28 days concurrently with neoantigen DNA vaccine. This is Treatment B. In the event the DNA vaccine production is delayed, patients will receive single agent nivolumab every 4 weeks beginning week 21 until the vaccine is ready
Receives: Biological: PROSTVAC-V; Biological: PROSTVAC-F; Drug: Nivolumab; Drug: Ipilimumab; Biological: Neoantigen DNA vaccine; Device: TriGrid Delivery System; Procedure: Tumor biopsy; Procedure: Peripheral blood; Procedure: Fecal samples; Procedure: Leukapheresis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety and tolerability of regimen as defined by incidence of adverse events

    -Adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0

    Measured: Through 100 days after completion of treatment (estimated to be 55 weeks)

  2. Immune response as measured by tetramers

    -MHC tetramers made against the identified neoantigens will be used to evaluate PBMC for neoantigen-reactive T cells

    Measured: Through completion of treatment (estimated to be 41 weeks)

  3. Immune response as measured by genomic studies

    -Laser capture microdissection will be performed to perform genomic studies on specific areas of tissue

    Measured: Through completion of treatment (estimated to be 41 weeks)

  4. Immune response as measured by flow cytometry

    -Multiparametric flow cytometry or CyTOF will be performed in parallel to evaluate for any shifts (in quality and quantity) in peripheral leukocyte subsets.

    Measured: Through completion of treatment (estimated to be 41 weeks)

  5. Safety and tolerability of regimen as defined by incidence of dose-limiting toxicities (DLTs)

    -DLT is defined as any unexpected, treatment-related grade 4 or 5 adverse event that occurs with increased severity or incidence outside of known, expected toxicities, that occur in the first 6 patients enrolled (safety lead-in cohort)

    Measured: Through 100 days after completion of treatment (estimated to be 55 weeks)

Secondary outcomes (8)

  1. Failure-free survival (FFS)

    -Defined as time from day 0 of treatment to evidence of at least one of the following: biochemical failure; radiographic or clinical progression either locally, in lymph nodes, or in distant metastases; or death from prostate cancer) compared to historical controls (ADT + docetaxel). Biochemical failure is defined as three consecutive rises (at lease one week apart) in PSA levels with the date of failure being the midpoint between the PSA nadir and the first PSA rise. Radiographic progression is defined as either RECIST1.1 or PCWG3 criteria.

    Measured: Through completion of follow-up (estimated to be 65 weeks)

  2. Milestone survival

    -Defined as the Kaplan-Meier survival probability

    Measured: Through completion of follow-up (estimated to be 65 weeks)

  3. Number of participants who have PSA responses at 30% reduction level

    • Baseline PSA prior to start of treatment will be compared to PSA nadir during treatment and then the investigators can calculate how many participants hit 30% reduction from pretreatment levels
    • Participants who enroll with no detectable PSA will be considered not evaluable for this outcome measure

    Measured: Through completion of treatment (estimated to be 41 weeks)

  4. Number of participants who have PSA responses at 50% reduction level

    • Baseline PSA prior to start of treatment will be compared to PSA nadir during treatment and then the investigators can calculate how many participants hit 50% reduction from pretreatment levels
    • Participants who enroll with no detectable PSA will be considered not evaluable for this outcome measure

    Measured: Through completion of treatment (estimated to be 41 weeks)

  5. Radiographic progression as determined by RECIST 1.1

    At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).

    Measured: Through completion of treatment (estimated to be 41 weeks)

  6. Radiographic progression as determined by Prostate Cancer Working Group 3 (PCWG3)

    • PCWG3 recommends that lymph nodes that were previously normal in size (< 1.0 cm) or pathologic in size must have grown by at least 5 mm in the short axis from baseline or nadir and be ≥ 1.0 cm in the short axis to be considered to have progressed. If the node progresses to ≥ 1.5 cm in the short axis, it is pathologic and measurable. Nodes that have progressed to between 1.0 and less than 1.5 cm are pathologic subject to clinical discretion and are nonmeasurable
    • The date of first metastasis is the date on which an unequivocal visceral lesion by RECIST 1.1 is determined
    • Documentation of radiographic evidence of metastatic disease should include the time of the unequivocal development of new sites on bone scintigraphy

    Measured: Through completion of treatment (estimated to be 41 weeks)

  7. Radiographic progression free survival (rPFS)

    -Radiographic progression-free survival (rPFS) is the time interval from baseline to the date when the first site of disease is found to progress (using a manifestation-specific definition of progression), or death, whichever occurs first. To better understand the effect of therapy on an individual site of disease, PCWG3 advises the date of progression in all specific sites be reported independently whether it is bone, nodes (pelvic or extrapelvic), visceral (lung, liver, adrenal, or CNS), or other.

    Measured: Through completion of treatment (estimated to be 41 weeks)

  8. Comparison of the immune correlates on matched tumor tissue and peripheral blood

    Laser capture microdissection will be performed to perform genomic studies on specific areas of tissue (eg tumor core, high TIL areas, tumor-stromal interface, etc). These will be correlated with multiplexed immunofluorescence studies, as well as assays on peripheral blood.

    Measured: Pre- and post-treatment (estimated to be 41 weeks)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 May 2018
  2. Study start14 Sep 2018
  3. Primary completion1 Apr 2022
  4. Study completion25 Jul 2022

Resources

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
19 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03532217
Sponsor's protocol ID
201808043
Other IDs
CA209-9MW
Status last verified
Aug 2022
First submitted
25 Apr 2018
Last updated
5 Aug 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
Yes
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing PROSTVAC-V, PROSTVAC-F and Nivolumab in people with Metastatic Hormone-Sensitive Prostate Cancer, run by Washington University School of Medicine 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 18 inclusion and 20 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: finished, as of the sponsor's last update on 5 Aug 2022. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Safety and tolerability of regimen as defined by incidence of adverse events (time frame: Through 100 days after completion of treatment (estimated to be 55 weeks)). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03532217.

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 5 Aug 2022.

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