Vector Delivery of the IL-12 Gene in Men With Prostate Cancer

This study is designed to determine the safety of IL-12 gene therapy for patients with recurrence of prostate cancer after radiation therapy and those with or without metastatic disease with a prostate gland intact. These, of course, would include recurrent prostate cancer after definitive radiation therapy. The prostate cancer will be treated with a prostatic injection of a replication-defective adenovirus vector delivering the IL-12 gene. Following virus injection, patients will be hospitalized for 23 hours for observation. Only one course of therapy will be administered. Each patient will be carefully monitored for toxic effects. Three to five patients will be tested with a low dose of virus and if there are no serious adverse side effects, the dose will be slowly escalated in subsequent groups of 3-5 patients or until unacceptable toxicity is reached. Effectiveness will be monitored by serum prostate-specific antigen (PSA), transrectal ultrasound of the prostate, prostate biopsy and comparison of survival times to historical survival times for patients with radiation recurrent prostate tumors. The primary objective of this initial study is to determine whether the treatment is associated with significant toxicity.

Sex

Male

Minimum age

18 Years

Inclusion Criteria:

* Men who have biopsy-proven local recurrence or persistence of cancer in the prostate gland with or without metastatic disease after the hormone therapy, cryosurgery, and/or the completion of definitive radiation therapy for at least one year.
* Patients must have evidence of biologically active local recurrence of tumor as demonstrated by a rising serum PSA level on at least 3 separate occasions at least 2 weeks apart, and that the serum PSA be below 50 ng/ml.
* The patient will possess the ability to give informed consent and express a willingness to meet all the expected requirements of the protocol for the duration of the study. (Informed Consent Document).
* Patients must have adequate baseline organ function as assessed by the following laboratory values before initiating the protocol.

  1. Adequate renal function with serum creatinine less than 1.5 mg/dl or creatinine clearance greater than 45 ml/min/m2.
  2. Platelet count greater than 100,000 platelets/mm3.
  3. Absolute neutrophil count greater than 1000/mm3.
  4. Hemoglobin greater than 8.5 mg/dl
  5. Normal partial thromboplastin time (PTT) and Pro-Thrombin Time (PT).
  6. Bilirubin less than 2.5 mg/dl, SGOT and SGPT less than 2.0x normal.

Exclusion Criteria:

* Acute infection: Acute infection is defined as any viral, bacterial or fungal infection, which requires specific therapy.
* Symptomatic metastasis.
* Metastatic lesions in the CNS/spinal cord or organs that could become life or function threatening within 3 months.

• BACKGROUNDShalev M, Kadmon D, Teh BS, Butler EB, Aguilar-Cordova E, Thompson TC, Herman JR, Adler HL, Scardino PT, Miles BJ. Suicide gene therapy toxicity after multiple and repeat injections in patients with localized prostate cancer. J Urol. 2000 Jun;163(6):1747-50. PMID 10799174
• BACKGROUNDFujita T, Timme TL, Tabata K, Naruishi K, Kusaka N, Watanabe M, Abdelfattah E, Zhu JX, Ren C, Ren C, Yang G, Goltsov A, Wang H, Vlachaki MT, Teh BS, Butler EB, Thompson TC. Cooperative effects of adenoviral vector-mediated interleukin 12 gene therapy with radiotherapy in a preclinical model of metastatic prostate cancer. Gene Ther. 2007 Feb;14(3):227-36. doi: 10.1038/sj.gt.3302788. Epub 2006 Oct 5. PMID 17024109