Treatment of Castration Resistant Prostate Cancer Using Multi-Targeted Recombinant Ad5 PSA/MUC1/Brachyury Based Immunotherapy Vaccines
Condition: Prostatic Neoplasms; Prostatic Cancer
MeSH terms: Prostatic Neoplasms
Intervention: ETBX-071; adenoviral PSA vaccine; ETBX-061; adenoviral MUC1 vaccine; ETBX-051; adenoviral brachyury vaccine
Intervention description: 5 x 10 to the eleventh power VP (standard dose), 1 x 10 to the eleventh power VP (DL-1), or 5 x 10 to the tenth power VP (DL-2) subcutaneous injection every 3 weeks for 3 immunizations.; 5 x 10 to the eleventh power VP (standard dose), 1 x 10 to the eleventh power VP (DL-1), or 5 x 10 to the tenth power VP (DL-2) subcutaneous injection every 3 weeks for 3 immunizations.; 5 x 10 to the eleventh power VP (standard dose), 1 x 10 to the eleventh power VP (DL-1), or 5 x 10 to the tenth power VP (DL-2) subcutaneous injection every 3 weeks for 3 immunizations.
Intervention MeSH terms: Vaccines
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: mCRPC; Therapeutic Cancer Vaccines; ETBX-071; ETBX-061; ETBX-051

Summary:

      Background:

      Metastatic castration resistant prostate cancer (mCRPC) keeps growing even when the amount of
      testosterone in the body is reduced to very low levels. mCRPC is incurable. Researchers want
      to develop vaccines to teach the immune system to target and kill cancer cells. They want to
      test three of these vaccines (ETBX-071, ETBX-061, and ETBX-051) against mCRPC.

      Objective:

      To test the safety of combination ETBX-071, ETBX-061, and ETBX-051 and to study their effects
      on the immune system.

      Eligibility:

      People ages 18 and older with mCRPC that has not responded to standard therapies

      Design:

      Participants will be screened with:

      Medical history

      Physical exam

      Blood, urine, and heart tests

      Computed tomography (CT) or magnetic resonance imaging (MRI) scans

      Bone scan

      Participants will get the vaccines as shots under the skin every 3 weeks for 3 doses. They
      may then have the shots every 8 weeks for up to 1 year.

      Participants will keep a diary to record any symptoms from the vaccines.

      Participants will have blood tests each time they get the vaccines. They will also have scans
      and other tests to measure the effect the vaccines have on their tumors.

      Participants will have a visit within 28 days after their last treatment. This includes a
      physical exam and blood and urine tests.

      Participants will then be contacted by phone every 3 months for the first year, every 6
      months for the next 2 years, and every 12 months for another 2 years.

      Participants will be asked to join a long-term follow up study.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

          -  Age more than or equal to 18 years (male).

          -  Ability to understand and provide signed informed consent that fulfills Institutional
             Review Board (IRB)s guidelines.

          -  Cytologically or histologically confirmed prostate cancer for which no curative
             standard approved therapy is available by either the Laboratory of Pathology at the
             National Institutes of Health (NIH) Clinical Center or Walter Reed National Military
             Medical Center at Bethesda prior to starting this study. If no pathologic specimen is
             available, patients may enroll with a pathologists report showing a histological
             diagnosis of prostate cancer and a clinical course consistent with the disease.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

          -  Subjects who have received prior prostate specific antigen (PSA), mucin1 (MUC1),
             and/or brachyury-targeted immunotherapy (e.g. vaccine) are eligible for this trial if
             this treatment was discontinued at least 3 months prior to enrollment.

          -  Resolution of all toxic side effects of prior chemotherapy, radiotherapy, or surgical
             procedures to National Cancer Institute (NCI) Common Terminology Criteria for Adverse
             Events (CTCAE) Grade less than or equal to1.

          -  Adequate hematologic function at screening, as follows:

          -  Absolute neutrophil count (ANC) greater than or equal to x 10 to the ninth power/L

          -  Hemoglobin more than or equa to 9 g/dL

          -  Platelets more than or equal to 75,000/microliter.

          -  Prothrombin (PT)-international normalized ratio (INR) < 1.5.

          -  Partial thromboplastin time (PTT) < 1.5 x upper limit of normal (ULN).

          -  Adequate renal and hepatic function at screening, as follows:

             --Serum creatine less than or equal to 1.5x upper limit of normal (ULN) OR creatinine
             clearance (CrCl) more than or equal to 40mL/min (if using the Cockcroft-Gault formula
             below):

               1. Female CrCl = [(140 - age in years) x weight in kg x 0.85] / [72 x serum
                  creatinine in mg/dL]

               2. Male CrCl = [(140 - age in years) x weight in kg x1.00] / [72 x serum creatinine
                  in mg/dL]

          -  Total bilirubin less than or equal to 1.5 x ULN OR in subjects with Gilberts syndrome,
             a total bilirubin less than or equal to x ULN

          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal
             to 2.5 x ULN, unless liver metastasis are present, then values must be less than or
             equal to 5 x ULN)

          -  The effects of ETBX-051, ETBX-061 and ETBX-071 vaccines on the developing human fetus
             are unknown. For this reason subjects must agree to use a condom and acceptable
             contraceptive method with their partner during the study and for one month after the
             last dose of vaccines.

          -  Ability to attend required study visits and return for adequate follow up, as required
             by this protocol.

          -  Castrate testosterone level (<50ng/dl or 1.7nmol /L)

          -  Metastatic disease documented by at least one of the following:

          -  Metastatic bone disease on an imaging study, or

          -  Soft tissue disease documented by computed tomography (CT)/magnetic resonance imaging
             (MRI)

          -  Progressive disease at study entry defined as one or more of the following criteria
             occurring in the setting of castrate levels of testosterone:

          -  Radiographic progression defined as any new or enlarging bone lesions or growing lymph
             node disease, consistent with prostate cancer

        OR

          -  PSA progression defined by sequence of rising values separated by >1 week (2 separate
             increasing values over a minimum of 2ng/ml (Prostrate Cancer Working Group 2 (PCWG2)
             PSA eligibility criteria). If patients had been on flutamide, PSA progression is
             documented 4 weeks or more after withdrawal. For patients on bicalutamide or
             nilutamide disease progression is documented 6 or more weeks after withdrawal. The
             requirement for a 4-6 week withdrawal period following discontinuation of flutamide,
             nilutamide or bicalutamide only applies to patients who have been on these drugs for
             at least the prior 6 months. For all other patients, they must stop bicalutamide,
             nilutamide or flutamide the day prior to enrollment.

          -  Patients must agree to continue to continuation of androgen deprivation therapy (ADT)
             with a gonadotropin-releasing hormone analogue/antagonist or bilateral orchiectomy

          -  Prior treatment with immunotherapy, hormonal therapy, radium 223, chemotherapy and/or
             other experimental therapy is allowed.

        EXCLUSION CRITERIA:

          -  Treatment with an investigational drug study within 28 days of before starting on
             study treatment.

          -  Subjects with concurrent cytotoxic chemotherapy or radiation therapy. There must be at
             least 28 days between any other prior chemotherapy (or radiotherapy) and study
             treatment. Prior antibody therapy must be discontinued 8 weeks prior to start of study
             treatment. Prior hormonal therapy can be discontinued 24 hours prior to start of study
             treatment.

          -  Any prior PSA, MUC1, and/or brachyury-targeted immunotherapy (e.g., vaccine) must have
             been discontinued at least 12 weeks before initiation of study treatment. Subjects
             must have recovered from all acute toxicities from prior treatment prior to screening
             for this study.

          -  Prior treatment with Adenovirus-Based vectors immunotherapy

          -  Known active brain or central nervous system metastasis, or seizures requiring
             anticonvulsant treatment, cerebrovascular accident, or transient ischemic attack (< 6
             months prior to enrollment).

          -  Subjects with a history of autoimmune disease (active or past), such as but not
             restricted to inflammatory bowel disease, systemic lupus erythematosus, ankylosing
             spondylitis, scleroderma, or multiple sclerosis. Autoimmune-related thyroid disease,
             type I diabetes and vitiligo are permitted if the condition is well controlled.

          -  Subjects with serious intercurrent chronic or acute illness, such as cardiac or
             pulmonary disease, hepatic disease, or other illness considered by the Investigator as
             high risk for investigational drug treatment.

          -  Subjects with a history of heart disease, such as congestive heart failure (class II,
             III, or IV defined by the New York Heart Association functional classification),
             history of unstable or poorly controlled angina, or history (< 1 year prior to
             enrollment) of ventricular arrhythmia.

          -  Subjects with a medical or psychological impediment that would impair the ability of
             the subject to receive therapy per protocol or impact ability to comply with the
             protocol or protocol-required visits and procedures.

          -  Presence of a known active acute or chronic infection, including human
             immunodeficiency virus (HIV, as determined by enzyme-linked immunosorbent assay
             [ELISA] and confirmed by western blot) and hepatitis B and hepatitis C virus (HBV/HCV,
             as determined by Hepatitis B surface antigen (HBsAg) and hepatitis C serology).

          -  Subjects on systemic intravenous or oral steroid therapy (or other immunosuppressive,
             such as azathioprine or cyclosporin A) are excluded on the basis of potential immune
             suppression. Subjects must have had at least 6 weeks of discontinuation of any steroid
             therapy (except that used as premedication for chemotherapy or contrast-enhanced
             studies) prior to enrollment. Physiologic (replacement) doses of steroids as well as
             nasal, topical or inhaled steroids are allowed.

          -  Subjects with known allergy or hypersensitivity to any component of the
             investigational product will be excluded.

          -  Subjects with acute or chronic skin disorders that will interfere with injection into
             the skin of the extremities or subsequent assessment of potential skin reactions will
             be excluded.

          -  Subjects vaccinated with a live (attenuated) vaccine (e.g., FluMist) or a killed
             (inactivated)/subunit vaccine (e.g., PNEUMOVAX, Fluzone) within 28 days or 14 days,
             respectively, of the first planned dose of ETBX vaccine.

          -  Patients with second malignancy within 3 years of enrollment; Patients curatively
             treated non-melanoma skin cancers or carcinoma in situ of the bladder, are not
             excluded.

          -  Use of herbal products that may decrease PSA levels (e.g. saw palmetto)

          -  Patients who have received radiation therapy, radionuclide therapy or undergone
             surgery within certain duration (4 weeks) of enrollment