Randomized Trial of Suicide Gene Therapy and Prostate Cancer
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms; Suicide
Intervention: Ad5-yCD/mutTKSR39rep-ADP; IMRT
Intervention description: Ad5-yCD/mutTKSR39rep-ADP (1 x 10^12 vp) on day 1 Plus Radiation - 40 x 2 Gy for a total dose of 80 Gy or 44 x 1.8 Gy for a total dose of 79.2 Gy Plus 2 week course (weekdays only) of 5-FC and vGCV prodrug therapy; 40 x 2 Gy for a total dose of 80 Gy or 44 x 1.8 Gy for a total dose of 79.2 Gy
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 44.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Prostatic Neoplasms; Prostate Cancer; Adenocarinomas; Tumors of the Prostate; Gene Therapy; IMRT

Summary:

      This is a randomized, controlled trial that will test the hypothesis that
      replication-competent adenovirus-mediated suicide gene therapy in combination with 80 Gy
      intensity modulated radiotherapy (IRMT)will improve freedom from failure (FFF) relative to 80
      Gy IMRT alone in patients with newly-diagnosed prostate cancer with an intermediate-risk
      profile.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Men with histologically-confirmed adenocarcinoma of the prostate within 180 days prior
             to registration. To be eligible, the subjects must have one of the following
             conditions:

               -  Stage T1 or T2, Gleason Score 7, PSA <= 20 ng/mL, Any number positive biopsy
                  cores

               -  Stage T1 or T2, Gleason Score 5 or 6, PSA >=10 ng/mL and <20 ng/mL, Any number
                  positive biopsy cores

               -  Stage T1 or T2, Gleason Score 5 or 6, PSA <10 ng/mL and >=50% positive biopsy
                  cores

          -  Negative lymph nodes as established by imaging, nodal sampling, or dissection within
             90 days prior to registration.

          -  No evidence of metastatic disease as evaluated by bone scan and CT scan of the abdomen
             and pelvis within 90 days prior to registration

          -  Karnofsky performance status >=70

          -  Subjects must have adequate baseline organ function, as assessed by the following
             laboratory values, within 30 days before initiating the study

          -  Adequate renal function with serum creatinine <=1.5 mg/dL or creatinine clearance >=45
             mL/min/m2.

          -  Platelet count > 100,000/μL.

          -  Absolute neutrophil count > 1,000/μL.

          -  Hemoglobin > 10.0 g/dL.

          -  Normal partial thromboplastin time (PTT) and prothrombin (PT).

          -  Bilirubin < 1.5 mg/dL; SGOT and SGPT < 2.5 times upper limit of normal (ULN).

          -  Men of child-producing potential must be willing to consent to use effective
             contraception while on treatment and for at least 3 months afterwards.

          -  Subjects must possess the ability to give informed consent and express a willingness
             to meet all of the expected requirements of the protocol for the duration of the
             study.

        Exclusion Criteria:

        Subjects with the following conditions will be excluded from the study:

          -  Stage >= T3.

          -  Prostate specific antigen (PSA) > 20 ng/mL.

          -  Gleason score >= 8.

          -  Prostate volume >120cc.

          -  Pathologically positive lymph nodes or nodes > 1.5 cm on imaging. Note: nodes > 1.5 cm
             but biopsy negative are allowed.

          -  Evidence of M1 metastatic disease.

          -  Prior invasive malignancy except for non-melanoma skin cancer within 5 years of
             enrollment.

          -  Prognosis for survival of < 5 years.

          -  Prior radical prostatectomy, cryosurgery for prostate cancer, or bilateral orchiectomy
             for any reason.

          -  Prior radiotherapy, including brachytherapy, to the region of the study cancer that
             would result in overlap of radiation fields.

          -  Prior or planned androgen suppression therapy or prior systemic chemotherapy for the
             study cancer. Note that prior chemotherapy for a different cancer is allowed; however,
             patients must be >2 years post-completion of chemotherapy at time of registration.
             Patients on Proscar therapy must stop to be eligible.

          -  Severe, active co-morbidity defined as:

          -  Unstable angina and/or congestive heart failure requiring hospitalization within the
             last 6 months.

          -  Transmural myocardial infarction within the last 6 months.

          -  Acute infection. Acute infection is defined by any viral, bacterial, or fungal
             infection that requires specific therapy within 72 hours of initiation of the study
             therapy.

          -  Positive serological test for HIV at baseline.

          -  Previous history of liver disease including hepatitis.

          -  Immunosuppressive therapy including systemic corticosteroids. Use of inhaled and
             topical corticosteroids is permitted.

          -  Impaired immunity or susceptibility to serious viral infections.

          -  Allergy to any product used in the protocol. (If the subject has an allergy to
             Ciprofloxacin, another antibiotic can be substituted at the discretion of the treating
             physician.

          -  Serious medical or psychiatric illness or concomitant medication, which, in the
             judgment of the principal investigator, might interfere with the subject's ability to
             respond to or tolerate the treatment or complete the trial.