CYT107 After Vaccine Treatment (Provenge®) in Patients With Metastatic Castration-Resistant Prostate Cancer
Condition: Castration Levels of Testosterone; Castration-Resistant Prostate Carcinoma; Metastatic Prostate Carcinoma; Stage IV Prostate Cancer
MeSH terms: Carcinoma; Prostatic Neoplasms
Intervention: Glycosylated Recombinant Human Interleukin-7; Laboratory Biomarker Analysis
Intervention description: Given SC; Correlative studies
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 54.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial studies how well glycosylated recombinant human interleukin-7
      (CYT107) after vaccine therapy works in treating patients with castration-resistant prostate
      cancer that has spread to other areas of the body or has not responded to at least one type
      of treatment. Biological therapies, such as glycosylated recombinant human interleukin-7, may
      stimulate the immune system in different ways and stop tumor cells from growing. Vaccines
      made from white blood cells mixed with tumor proteins may help the body build an effective
      immune response to kill tumor cells. It is not yet known whether glycosylated recombinant
      human interleukin-7 works better with or without vaccine therapy in treating prostate cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer
             (mCRPC)

          -  Patients must have successfully completed therapy with sipuleucel-T within 3-7 days of
             planned CYT107 study drug treatment

          -  Assessable disease with a positive bone scan and/or measurable disease on computed
             tomography (CT) scan and/or magnetic resonance imaging (MRI) of the abdomen and pelvis

          -  Prior orchiectomy or must be on ongoing luteinizing hormone-releasing hormone (LHRH)
             agonist or antagonist (e.g., degarelix) therapy

          -  No ongoing anti-androgen therapy; patients must be off anti-androgen therapy for at
             least 30 days

          -  Patients receiving any other hormonal therapy, including any dose of megestrol acetate
             (Megace), Proscar (finasteride), any herbal product known to decrease prostate
             specific antigen (PSA) levels (e.g. saw palmetto, PC-SPES), or any systemic
             corticosteroid, must discontinue the agent for at least 30 days prior to study
             treatment

          -  Absolute neutrophil count (ANC) >= 1500/uL

          -  Bilirubin < 1.5 x upper limit of normal (ULN)

          -  Hemoglobin >= 10 g/dL

          -  Platelets >= 100,000/mcL

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN

          -  Creatinine clearance >= 60 mL/min by the Cockcroft-Gault equation

          -  Testosterone =< 50 ng/dL (documented at any time while on LHRH agonist or antagonists
             or s/p orchiectomy)

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 or a Karnofsky
             performance status of >= 80%

          -  Life expectancy of at least 6 months

          -  Prior local radiation therapy must be completed at least 30 days prior to enrollment
             and the patient must have recovered from all toxicity

          -  Prior "systemic" radiopharmaceuticals (strontium, samarium, radium 223 dichloride)
             must be completed >= 8 weeks prior to enrollment

          -  Patients must agree to use 2 methods of adequate contraception for the duration of
             study participation, and for four months after discontinuing therapy

          -  Ability to understand and the willingness to sign a written informed consent document

        Exclusion Criteria:

          -  Prior chemotherapy for castration resistant prostate cancer; neoadjuvant chemotherapy
             and chemotherapy given for hormone sensitive prostate cancer are allowed

          -  Prior investigational immunotherapy

          -  Prostate cancer pain requiring regularly scheduled narcotics

          -  Pathologic long-bone fractures, imminent pathologic long-bone fracture (cortical
             erosion on radiography > 50%) or spinal cord compression

          -  Current treatment with systemic steroid therapy (inhaled/topical steroids are
             acceptable); systemic corticosteroids must be discontinued for at least 30 days prior
             to first CYT107 injection

          -  Known central nervous system metastases

          -  Documented cirrhosis or documented acute hepatitis; Note: a positive hepatitis B
             serology indicative of previous immunization (i.e., hepatitis B surface antibody
             [HBsAb] positive and hepatitis B core antibody [HBcAb] negative), or a fully resolved
             acute hepatitis B virus (HBV) infection is not an exclusion criterion

          -  History of severe asthma, as defined by prior or current use of systemic
             corticosteroids for disease control, with the exception of physiological replacement
             doses of cortisone acetate or equivalent, as defined by a dose of 10 mg or less

          -  Medical or psychiatric illness that would, in the opinion of the investigator,
             preclude participation in the study or the ability of patients to provide informed
             consent for themselves

          -  Cardiovascular disease that meets one of the following: congestive heart failure (New
             York Heart Association class III or IV), active angina pectoris, or recent myocardial
             infarction (within the last 6 months)

          -  Concurrent or prior malignancy except for the following:

               -  Adequately treated basal or squamous cell skin cancer

               -  Adequately treated stage I or II cancer from which the patient is currently in
                  complete remission

               -  Any other cancer from which the patient has been disease-free for 5 years

          -  Known human immunodeficiency virus (HIV) or other history of immunodeficiency
             disorder; HIV-positive patients on combination antiretroviral therapy are ineligible

          -  Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for
             treatment of either a psychiatric or medical (e.g. infectious) illness

          -  Any underlying medical or psychiatric condition, which in the opinion of the
             investigator will make the administration of CYT107 hazardous or obscure the
             interpretation of adverse events (AEs), such as a condition associated with frequent
             diarrhea

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to CYT107

          -  Patients who have received prior immunosuppressive therapy within 30 days prior to
             enrollment

          -  Active (as defined by requiring immunosuppressive therapy) or history of clinically
             significant autoimmune disease (as defined by previously requiring immunosuppressive
             therapy)

          -  Patients who have received hepatotoxic drugs less than 7 days prior to enrollment

          -  Patients who have received prior biologic agents less than 30 days prior to enrollment

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or
             psychiatric illness/social situations that would limit compliance with study
             requirements

          -  Patients who have a history of any hematopoietic malignancy

          -  History of pulmonary disease such as emphysema or chronic obstructive pulmonary
             disease (COPD), (forced expiratory volume [FEV] > 60% of predicted for height and age
             required in patients with prolonged smoking history or symptoms of respiratory
             dysfunction)