Ensayos clínicos

Inclusion Criteria

• Must have histologically confirmed diagnosis of prostate cancer (adenocarcinoma of the prostate)
• Must have metastatic disease as evidenced by the presence of soft tissue and/or bone metastases on imaging studies (computed tomography [CT] of abdomen/pelvis, bone scintigraphy)
• Must have castrate-resistant disease, defined as
  • Received standard of care androgen deprivation treatment before trial entry (surgical castration versus gonadotropin-releasing hormone [GnRH] analogue or antagonist treatment)
  • If receiving GnRH analogue or antagonist must continue this treatment throughout the time on this study
  • Must have been treated previously with a nonsteroidal antiandrogen, with evidence of subsequent disease progression
  • Must be off use of anti-androgen for at least 4 weeks (for flutamide) or 6 weeks (for bicalutamide or nilutamide) prior to randomization
  • If demonstrates an anti-androgen withdrawal response, defined as a ≥ 25% decline in PSA within 4-6 week of stopping a nonsteroidal antiandrogen are not eligible until the PSA rises above the nadir observed after antiandrogen withdrawal
  • Must have castration levels of testosterone (< 50 ng/dL) within 4 weeks prior to randomization
• Must have progressive disease while receiving ADT as defined by any one of the following as per the Prostate Cancer Clinical Trials Working Group 2 (PCWG2)
  • At least two consecutive rises in serum PSA, obtained at a minimum of 1-week intervals, and each value ≥ 2.0 ng/mL
  • ≥ 50% increase in the sum of the cross products of all measurable lesions or the development of new measurable lesions by RECIST criteria version 1.1
  • The greatest diameter of a target lesion must be at least 1.0 cm by CT scan (1.5 cm in shortest axis for lymph nodes)
  • The appearance of two or more new areas of uptake on bone scan consistent with metastatic disease compared to previous imaging during castration therapy
    • The increased uptake of pre-existing lesions on bone scan will not be taken to constitute progression, and ambiguous results must be confirmed by other imaging modalities (e.g. X-ray, CT or magnetic resonance imaging [MRI])
• Must not have poor prognosis features suggested by the following required information
  • Presence of visceral (non-lymph node, non-bone) metastases
  • Poor performance status (Eastern Cooperative Oncology Group [ECOG] performance status [PS] of 2 or greater)
  • Alkaline phosphatase (IU/L) > 2 x institutional upper limit of normal
  • Lactate dehydrogenase (LDH) (U/L) > 2 x institutional upper limit of normal
• Must have an ECOG performance status of 0 or 1
• White blood cell (WBC) count ≥ 2000/mm^3
• Absolute neutrophil count (ANC) ≥ 1500/mm^3
• Platelet count ≥ 100,000/mm^3
• Creatinine ≤ 2.0 mg/dL
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 1.5 x institutional upper limit of normal (ULN)
• Total bilirubin < institutional upper limit of normal (ULN)
• Must have completed any prior treatments (apart from androgen deprivation as previously described) ≥ 4 weeks prior to randomization and have recovered (to < grade 2) from any acute toxicities attributed to this prior treatment
• Must agree to use an accepted and effective method of contraception prior to study entry and for the duration of study participation (or at least 4 months after the last vaccination in subjects receiving vaccine series)
• if patient impregnates a woman while participating in this study, he should inform his treating physician immediately
• Must not be receiving any other investigational agents or be receiving concurrent anticancer therapy other than ADT
• Must not have been treated with a prior anti-cancer vaccine (including sipuleucel-T, Provenge®)
• Must not have received treatment with any of the following medications within 4 weeks of randomization or while on study
  • Systemic corticosteroids (excluding prednisone and dexamethasone administered as part of study protocol)
    • Inhaled, intranasal or topical corticosteroids are acceptable
  • Steroid eye drops (contraindicated for 2 weeks prior to vaccination and for at least 4 weeks after vaccinia vaccination)
  • PC-SPES
  • Saw palmetto
  • Megestrol
  • Ketoconazole
  • 5-alpha-reductase inhibitors
    • If already taking 5-alpha-reductase inhibitors at least 28 days prior to randomization,  may stay on these agents throughout the course of therapy, but these should not be started while patients are on study
  • Diethyl stilbestrol
  • Any other hormonal agent or supplement with possible anti-cancer activity
• Must not have been treated with external beam radiation therapy within 4 weeks of randomization
• Must not have received prior radiation therapy to > 30% of bone marrow
• Must not have had surgery within 4 weeks of randomization
• Must not have received prior chemotherapy within 6 months of randomization
  • Prior and/or concurrent treatment with bisphosphonates, however, is permitted
• Must not have received prior chemotherapy for metastatic prostate cancer
• Cannot have a known history of human immunodeficiency virus (HIV) 1 or 2, human T-lymphotropic virus (HTLV)-1, hepatitis B, or hepatitis C (or any other potentially immunosuppressive infection)
  • Must have negative serologic testing for HIV, hepatitis B surface antigen, and hepatitis C
• Cannot have a history of autoimmune disease requiring active immunosuppressive therapy or have organ dysfunction ≥ grade 2 as a result of known autoimmune disease
• Must have antinuclear antibodies (ANA) titer < 1:320
• Must not have undergone splenectomy
• Must not have other active malignancies other than non-melanoma skin cancers or carcinoma in situ of the bladder
  • A history of other cancers adequately treated and recurrence-free for ≥ 3 years is eligible
• Cannot have a known allergy to eggs
• Cannot have a known intolerance or allergic reactions to docetaxel or compounds of similar chemical or biologic composition
• Cannot have a known history of allergy or intolerable reaction to a previous vaccinia virus vaccination (e.g., smallpox)
• Patient or those who share housing or have close physical contact with the patient cannot have close physical contact to persons with the following conditions within 3 weeks after potential vaccinia immunization
  • A history of eczema, active eczema or other acute, chronic or exfoliative skin conditions, including Darier's disease (e.g. atopic dermatitis, burns, impetigo, varicella zoster, severe acne, or open wounds)
  • Pregnant or nursing women
  • Children under 3 years of age
  • Immunodeficient or immunosuppressed persons (e.g. HIV, or treated for other diseases with immunosuppressive agents)
  • Any other moderate or severe acute illness until the illness resolves
  • Patients who would be unable to avoid these conditions for a 3-week period are not eligible
    • Should also refer to the patient instruction sheet for vaccinia virus
• Cannot have known brain metastases
• Cannot have a known history of recent (within 6 months) stroke, myocardial infarction, unstable angina, New York Heart Association class II-IV congestive heart failure, or significant cardiomyopathy requiring treatment
• Cannot take known strong inducers or inhibitors of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) within 2 weeks of beginning docetaxel through its discontinuation
  • Substrates of CYP3A4 with a narrow therapeutic/toxicity window may be used with caution, with prior approval of the study chair or institution's principal investigator (PI)