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Neoadjuvant PROSTVAC-VF With or Without Ipilimumab for Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02506114
Recruitment Status : Active, not recruiting
First Posted : July 22, 2015
Last Update Posted : August 26, 2019
Information provided by (Responsible Party):
Lawrence Fong, University of California, San Francisco

Tracking Information
First Submitted Date  ICMJE July 21, 2015
First Posted Date  ICMJE July 22, 2015
Last Update Posted Date August 26, 2019
Actual Study Start Date  ICMJE June 7, 2016
Actual Primary Completion Date May 6, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 21, 2015)
CD3+ T cell Immune response [ Time Frame: Up to 2 years ]
Immunohistochemistry (IHC)
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02506114 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 21, 2015)
  • Immunologic infiltration [ Time Frame: Up to 2 years ]
    IHC assessment (CD4+, CD8+, CD56+, FOXP3, etc.)
  • Circulating effector T cells [ Time Frame: Up to 2 years ]
    flow cytometry assessment of peripheral blood mononuclear cells
  • Regulatory T cells [ Time Frame: Up to 2 years ]
    flow cytometry assessment of peripheral blood mononuclear cells
  • Adverse Events [ Time Frame: Up to 2 years ]
    NCI CTCAE v.4.03
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Neoadjuvant PROSTVAC-VF With or Without Ipilimumab for Prostate Cancer
Official Title  ICMJE 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
Brief 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 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Prostatic Neoplasms
Intervention  ICMJE
  • Biological: PROSTVAC V/F
    PROSTVAC-V/F is a PSA (prostate-specific antigen)-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.
  • Drug: Ipilimumab
Study Arms  ICMJE
  • Experimental: Arm A
    PROSTVAC-V: 2 x 10^8pfu; subcutaneous; Day 1. PROSTVAC-F: 1 x 10^9pfu; subcutaneous; Days 15, and 36.
    Intervention: Biological: PROSTVAC V/F
  • Experimental: Arm B
    Ipilimumab: 3 mg/kg; intravenously; Days 1 and 21.
    Intervention: Drug: Ipilimumab
  • Experimental: Arm C
    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.
    • Biological: PROSTVAC V/F
    • Drug: Ipilimumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: August 21, 2019)
Original Estimated Enrollment  ICMJE
 (submitted: July 21, 2015)
Estimated Study Completion Date  ICMJE December 31, 2019
Actual Primary Completion Date May 6, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 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
  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/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
  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 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT02506114
Other Study ID Numbers  ICMJE 14559
NCI-2017-01679 ( Registry Identifier: NCI Clinical Trials Reporting Program (CTRP) )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Lawrence Fong, University of California, San Francisco
Study Sponsor  ICMJE University of California, San Francisco
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Lawrence Fong, MD University of California, San Francisco
PRS Account University of California, San Francisco
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP