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
PC. 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, 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.
- Patients must have histologically confirmed adenocarcinoma of the prostate without
previous therapy for PC.
- Treatment-naïve AND
- Undergoing RP as initial, locally definitive therapy for PC AND
- Eligible for RP in a 3 month timeframe AND
- Consentable for RP
- Subject's prostate tissue biopsy, with a minimum of 6 cores, is available and
appropriate for IHC evaluation, and subject consents to provide tissue for study
- Age ≥ 18 years
- Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- Subject has adequate organ function, defined as:
- White blood cell (WBC) count ≥ 3,000/mcL
- Absolute neutrophil count (ANC) ≥ 1,500/mcL
- Platelet count ≥ 100,000/mcL
- Hemoglobin (Hgb) ≥ 10.0 g/dL
- Creatinine ≤ 1.5x institutional ULN
- Total bilirubin ≤ 1.5 x institutional ULN
- Alanine aminotransferase (ALT) ≤ 1.5 x institutional ULN
- Aspartate aminotransferase (AST) ≤ 1.5 x institutional ULN
- PT/INR, 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
- 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).
- 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 at any time prior to study
- 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.
- 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.
- 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
- Persons with vitiligo are not excluded.
- Diabetics are not excluded if the condition is well controlled
- Hemoglobin A1C < 7.0
- No evidence of end-organ damage due to diabetes, such as diabetic retinopathy,
nephropathy, or neuropathy
- 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
- 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-V/F or
ipilimumab hazardous, 2) obscure the interpretation of 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.