177Lu Radiolabeled Monoclonal Antibody HuJ591 (177Lu-J591) and Ketoconazole in Patients With Prostate Cancer
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: 177Lu-J591; Ketoconazole; Hydrocortisone; 111In-J591
Intervention description: 177Lu-J591 70 mCi/m2 on day 29 (+/- 2 days) of treatment; Ketoconazole at a dose of 400 mg (two 200 mg tabs) to be taken orally (preferably on an empty stomach) three times per day (total daily dose of 1200 mg); Hydrocortisone at a dose of 20 mg orally each morning, 10 mg orally each evening (total daily dose of 30 mg); 111In-J591 at a dose of 5 mCi on day 29 (+/- 2 days) of treatment
Intervention MeSH terms: Ketoconazole; Hydrocortisone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 55.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Prostate

Summary:

      The purpose of this study is to test the effectiveness of the experimental drug, 177Lu-J591
      in combination with ketoconazole and hydrocortisone against prostate cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed adenocarcinoma of the prostate previously
             treated with surgery and/or radiotherapy.

          -  Biochemical progression (rising PSA) after medical or surgical castration

          -  High risk of systemic progression defined as:

               1. Rising PSA as defined above and either:

               2. Absolute PSA > 20 ng/mL AND/OR

               3. PSA doubling time < 8 months

          -  No evidence of local recurrence or distant metastases

          -  Age >18 years.

          -  Serum testosterone < 50 ng/ml

          -  Patients capable of fathering children must agree to use an effective method of
             contraception for the duration of the trial.

          -  Subjects on bisphosphonate therapy must be on a stable dose and must have started
             therapy > 4 weeks prior to protocol therapy.

          -  Ability to understand and the willingness to sign a written informed consent document.

        Exclusion Criteria:

          -  Use of red blood cell or platelet transfusions within 4 weeks of treatment

          -  Use of hematopoietic growth factors within 4 weeks of treatment

          -  Prior cytotoxic chemotherapy and/or radiation therapy within 4 weeks of treatment

          -  Prior radiation therapy encompassing >25% of skeleton (see Appendix C)

          -  Prior treatment with 89Strontium or 153Samarium containing compounds (e.g. Metastron®,
             Quadramet®)

          -  Platelet count <150,000/mm3 or known primary qualitative platelet disorder

          -  Absolute neutrophil count (ANC) <2,000/mm3

          -  Hematocrit <30 percent and Hemoglobin < 10 g/dL

          -  Abnormal coagulation profile (PT or INR, PTT > 1.3x ULN) unless on therapeutic
             anticoagulation - see concomitant meds section

          -  Serum creatinine >2.5 mg/dL

          -  AST (SGOT) >2x ULN

          -  Bilirubin (total) >1.5x ULN; subjects with Gilbert's syndrome will be allowed if
             direct bilirubin is within institutional normal limits

          -  Active serious infection

          -  Active angina pectoris or NY Heart Association Class III-IV

          -  ECOG Performance Status > 2

          -  Life expectancy <12 months

          -  History of deep vein thrombosis and/or pulmonary embolus within 1 month of study entry

          -  Other serious illness(es) involving the cardiac, respiratory, CNS, renal, hepatic or
             hematological organ systems which might preclude completion of this study or interfere
             with determination of causality of any adverse effects experienced in this study

          -  Prior investigational therapy (medications or devices) within 4 weeks of treatment.
             Furthermore, other investigational therapy is not permitted during the treatment
             phase.

          -  Prior use of ketoconazole for the purposes of prostate cancer therapy for greater than
             1 month

          -  Known history of HIV. The effects of J591 are unknown in this population. Furthermore,
             ketoconazole has many well-described drug-drug interactions which could affect
             antiviral therapy. If necessary, this population will be studied separately.

          -  Currently active other malignancy other than non-melanoma skin cancer. Patients are
             considered not to have "currently active" malignancy if they have completed any
             necessary therapy and are considered by their physician to be at less than 30% risk of
             relapse.

             - Known history of known myelodysplastic syndrome

          -  Adrenal hormone inhibitors (other than ketoconazole) within 4 weeks prior to study
             enrollment

          -  Finasteride (Propecia® or Proscar®) or dutasteride (Avodart®) within 4 weeks of
             enrollment

          -  Patients on corticosteroids prior to enrollment must have either discontinued and
             shown biochemical progression or have biochemical progression on a stable dose