Neoantigen DNA Vaccine in Combination With Nivolumab/Ipilimumab and PROSTVAC in Metastatic Hormone-Sensitive Prostate Cancer
NCT ID: NCT03532217
Last Updated: 2022-08-05
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE1
19 participants
INTERVENTIONAL
2018-09-14
2022-07-25
Brief Summary
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Detailed Description
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Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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PROSTVAC/Ipilimumab/Nivolumab/Neoantigen DNA vaccine
* 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
PROSTVAC-V
-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-F
-Fowlpox virus which does not replicate in human cells and has been engineered to encode the same sequences present in PROSTVAC-V.
Nivolumab
-Nivolumab is a human monoclonal antibody (mAb)
Ipilimumab
-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 vaccine
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 System
-Electroporation device
Tumor biopsy
-Pre-treatment, post-treatment A (optional), and end of treatment
Peripheral blood
-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 samples
-Post chemo/pre-treatment A, post-treatment A, pre-treatment B, post-treatment B
Leukapheresis
* Post-treatment A/pre-treatment B
* Mid-Treatment B, after Cycle 9 Day 1 and prior to Cycle 10 Day 1
* End of treatment
Interventions
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PROSTVAC-V
-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-F
-Fowlpox virus which does not replicate in human cells and has been engineered to encode the same sequences present in PROSTVAC-V.
Nivolumab
-Nivolumab is a human monoclonal antibody (mAb)
Ipilimumab
-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 vaccine
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 System
-Electroporation device
Tumor biopsy
-Pre-treatment, post-treatment A (optional), and end of treatment
Peripheral blood
-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 samples
-Post chemo/pre-treatment A, post-treatment A, pre-treatment B, post-treatment B
Leukapheresis
* Post-treatment A/pre-treatment B
* Mid-Treatment B, after Cycle 9 Day 1 and prior to Cycle 10 Day 1
* End of treatment
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
* 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.
Exclusion Criteria
* 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
* 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.
18 Years
MALE
No
Sponsors
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Bristol-Myers Squibb
INDUSTRY
Prostate Cancer Foundation
OTHER
The Foundation for Barnes-Jewish Hospital
OTHER
Bavarian Nordic
INDUSTRY
Washington University School of Medicine
OTHER
Responsible Party
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Principal Investigators
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Russell Pachynski, M.D.
Role: PRINCIPAL_INVESTIGATOR
Washington University School of Medicine
Locations
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Washington University School of Medicine
St Louis, Missouri, United States
Countries
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Related Links
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Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
Other Identifiers
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CA209-9MW
Identifier Type: OTHER
Identifier Source: secondary_id
201808043
Identifier Type: -
Identifier Source: org_study_id
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