Neoadjuvant PROSTVAC-VF With or Without Ipilimumab for Prostate Cancer
Condition: Prostatic Neoplasms
MeSH terms: Prostatic Neoplasms
Intervention: PROSTVAC V/F; Ipilimumab
Intervention description: 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.
Intervention MeSH terms: Ipilimumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 15.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: prostate

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. 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.
    

Eligibility criteria:

        Inclusion Criteria:

        For a subject to be eligible for participation in this study, all of the following criteria
        must be satisfied:

          1. 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

          2. 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.

          3. Age ≥ 18 years

          4. Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

          5. 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

          6. No known history of human immunodeficiency virus (HIV) 1 and 2, human T-cell
             lymphotropic virus (HTLV)-I/II, and Hepatitis B and C.

          7. Ability to understand a written informed consent document, and the willingness to sign
             it.

          8. 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.

        Exclusion Criteria:

        A subject will not be eligible for participation in this study if any of the following
        criteria apply.

          1. Subject's biopsy specimen reveals neuroendocrine or small cell features.

          2. Subject has any evidence of metastatic disease (pre-operative staging will be
             undertaken per urologic standard of care) as deemed by the Investigator.

          3. 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.

          4. 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).

          5. Subject has received prior radiation therapy or chemotherapy for prostate cancer.

          6. 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.

          7. Active atopic dermatitis or skin condition that disrupts the epidermis

          8. Inflammatory eye disease requiring steroid treatment

          9. History of prior solid organ or bone marrow transplant

         10. Previous history of hypersensitivity to eggs or allergy or untoward reaction to prior
             vaccinia (smallpox) vaccination.

         11. Splenectomy

         12. 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

         13. Subject's close household contacts include children less than the age of three

         14. 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:

                    1. Hemoglobin A1C < 7.0, and

                    2. No evidence of end-organ damage due to diabetes, such as diabetic
                       retinopathy, nephropathy, or neuropathy

                    3. 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.

         15. 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.

         16. 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.

         17. Subject has a history of allergic reactions attributed to compounds of similar
             chemical or biologic composition to PROSTVAC-V/F or ipilimumab.

         18. 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.

         19. 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.

         20. 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.

         21. 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.