Docetaxel and PROSTVAC for Metastatic Castration-Sensitive Prostate Cancer
Condition: Prostate Cancer; Prostate Neoplasms; Neoplasms, Prostatic
MeSH terms: Prostatic Neoplasms; Neoplasms
Intervention: PROSTVAC-V; PROSTVAC-F; Docetaxel
Intervention description: It is a recombinant vaccinia virus vector vaccine containing the genes for human prostate-specific antigen (PSA) and three co-stimulatory molecules (cluster of differentiation 80 (B7.1), intercellular adhesion molecule 1 (ICAM-1), and lymphocyte function-associated antigen 3 (LFA-3). It will be given subcutaneously, 2x10(8) infectious units.; It is a recombinant fowlpox virus vector vaccine containing the genes for human prostate-specific antigen (PSA) and three co-stimulatory molecules (cluster of differentiation 80 (B7.1), intercellular adhesion molecule 1 (ICAM-1), and lymphocyte function-associated antigen 3 (LFA-3). It will be given subcutaneously, 1x10(9) infectious units.; It is commercially available. It will be administered at 75 mg/m(2) intravenously.
Intervention MeSH terms: Docetaxel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 74.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: PSA; Vaccine; Immunotherapy; Immune Response; Androgen Deprivation Therapy

Summary:

      Background:

      Metastatic castrate-sensitive prostate cancer is cancer that has spread beyond the prostate
      area. It can be controlled by lowering the amount of testosterone in the body. This is called
      androgen deprivation therapy (ADT). The vaccine PROSTVAC might help the immune system kill
      cancer cells. Researchers want to add PROSTVAC and docetaxel chemotherapy to ADT. They think
      this may work better against prostate cancer than ADT alone.

      Objective:

      To test if adding PROSTVAC and docetaxel to ADT works better against prostate cancer than ADT
      alone.

      Eligibility:

      Men ages 18 years and over with metastatic castrate-sensitive prostate cancer

      Design:

      Participants will be screened with:

      Physical exam

      Medical history

      Blood tests

      Possible computed tomography (CT), magnetic resonance imaging (MRI), or bone scan:
      Participants lie in a machine. The machine takes pictures of the body.

      Electrocardiogram: Soft electrodes are stuck to the skin to record heart signals.

      Participants will have 2 optional tumor biopsies during the study.

      Participants will join 1 of 2 groups. Both groups will get:

      ADT

      Docetaxel by vein

      Steroids by mouth or vein before each docetaxel infusion

      PROSTVAC injection

      Both groups first have ADT. One to 4 months after, they have:

      Group A:

      Docetaxel every 3 weeks for 6 cycles

      PROSTVAC 3 weeks after the last infusion

      Booster injections 2 weeks later and then every 3 weeks, for 6 boosters total

      Group B:

      PROSTVAC

      Booster 2 weeks later

      Docetaxel hours later

      Docetaxel and the booster every 3 weeks for 6 cycles

      Participants will have a visit 4-5 weeks after the last treatment. They will then have visits
      every 12 weeks.

      Participants will be followed for up to 15 years. This includes physical exams every year for
      5 years.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

          -  Documented histopathological confirmation of prostate cancer-from a Clinical
             Laboratory Improvement Amendments (CLIA) certified laboratory.

          -  Patients must have metastatic disease, defined as at least one lesion on bone scan or
             at least one lesion that are measurable per Response Evaluation Criteria in Solid
             Tumors (RECIST) 1.1. (Patients who have metastatic disease by these criteria prior to
             ADT, but then have changes after androgen deprivation therapy (ADT) that diminish the
             size of these lesions or changes on bone scan are still eligible.)

          -  Patients must have a performance status of 0 to 2 according to the Eastern Cooperative
             Oncology Group (ECOG) criteria

          -  Patients must have adequate bone marrow, hepatic, and renal function with:

               -  Absolute neutrophil count (ANC) greater than or equal to 1500/microL, without
                  cerebrospinal fluid (CSF) support

               -  Platelets greater than or equal to 100,000/microL

               -  Aspartate aminotransferase (AST)/Serum glutamic-oxaloacetic transaminase (SGOT)
                  less than or equal to 2.5 times upper limit of normal (ULN);

               -  Alanine aminotransferase (ALT)/Serum glutamic-pyruvic transaminase (SGPT) less
                  than or equal to 2.5 times upper limit of normal (ULN);

               -  Total serum bilirubin less than or equal to 1.5 times upper limit of normal
                  (ULN), OR in patients with Gilbert's syndrome, a total bilirubin less than or
                  equal to 3.0)

               -  Serum albumin greater than or equal to 2.8 g/dL

               -  Lipase < 2.0 times the upper limit of normal and no radiologic or clinical
                  evidence of pancreatitis

               -  Creatinine less than or equal to 1.5 times institutional upper limits of normal

        OR

        Creatinine clearance of greater than or equal to 50 ml/min/1.73 m(2) for patients with
        creatinine levels above institutional normal by 24-hour urine.

          -  Willing to travel to the National Institutes of Health (NIH) for follow-up visits

          -  18 years of age or older.

          -  Able to understand and sign informed consent.

          -  May have had up to 24 months of ADT (testosterone suppression therapy in the
             nonmetastatic setting) and are at least 12 months removed from treatment

          -  Men treated or enrolled on this protocol must also agree to use adequate
             contraception, prior to the study, for the duration of study participation, and 4
             months after completion. Sexually active subjects and their female partners must agree
             to use medically accepted barrier methods of contraception (e.g., male or female
             condom) during the course of the study and for 4 months after the last dose of study
             drug(s), even if oral contraceptives are also used. All subjects of reproductive
             potential must also agree to use both a barrier method and a second method of birth
             control during the course on the study and for 4 months after the last dose of study
             drug(s). Should a woman become pregnant or suspect she is pregnant while her partner
             is participating in this study, she should inform her treating physician immediately.

          -  Must have started ADT for metastatic disease within 134 days (for Arm A and B) or
             within 28 days (for Arm C).

        EXCLUSION CRITERIA:

          -  Immunocompromised status due to:

               -  Human immunodeficiency virus (HIV) positivity.

               -  Active autoimmune diseases such as Addison's disease, Hashimoto's thyroiditis,
                  systemic lupus erythematosus, Sjogren's syndrome, scleroderma, myasthenia gravis,
                  Goodpasture syndrome or active Grave's disease. Patients with a history of
                  autoimmunity that has not required systemic immunosuppressive therapy or does not
                  threaten vital organ function including central nervous system (CNS), heart,
                  lungs, kidneys, skin, and gastrointestinal (GI) tract will be allowed.

               -  Other immunodeficiency diseases

          -  Chronic administration (defined as daily or every other day for continued use > 14
             days) of corticosteroids deemed systemic by investigator within 28 days before the
             first planned dose of PROSTVAC. Use of inhaled steroids, nasal sprays, and topical
             creams for small body areas is allowed.

          -  Evidence of rising prostate-specific antigen (PSA) on ADT

          -  Serious intercurrent medical illness that, in the judgment of the investigator, would
             interfere with patient's ability to carry out the treatment program.

          -  Other medications used for urinary symptoms including 5-alpha reductase inhibitors
             (finasteride and dutasteride) and alternative medications known to alter PSA (e.g.
             phytoestrogens and saw palmetto)

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to poxviral vaccines (e.g., vaccinia vaccine)

          -  Known allergy to eggs, egg products, aminoglycoside antibiotics (for example,
             gentamicin or tobramycin).

          -  History of atopic dermatitis or active skin condition (acute, chronic, exfoliative)
             that disrupts the epidermis

          -  Previous serious adverse reactions to smallpox vaccination

          -  Unable to avoid close contact or household contact with the following high-risk
             individuals for three weeks after the Day 1 vaccination: (a) children less than or
             equal to 3 years of age, (b) pregnant or nursing women, (c) individuals with prior or
             concurrent extensive eczema or other eczemoid skin disorders, or (d) immunocompromised
             individuals, such as those with human immunodeficiency virus (HIV).

          -  Receipt of an investigational agent within 28 days (or 60 days for an antibody-based
             therapy) before the first planned dose of study drugs.

          -  Patients who test positive for hepatitis B virus (HBV) or hepatitis C virus (HCV)

          -  Uncontrolled hypertension (systolic blood pressure (SBP)>170/ diastolic blood pressure
             (DBP)>105)

          -  Patients who have had prior chemotherapy for prostate cancer.

          -  The subject has had evidence within 2 years of the start of study treatment of another
             malignancy which required systemic treatment (with the exception of nonmelanoma skin
             cancers or carcinoma in situ of the bladder).

          -  The subject has active brain metastases or epidural disease.

          -  Patients with greater than or equal to grade 2 peripheral neuropathy at baseline.

          -  Patients with history of splenectomy