Phase 1 Trial of Interleukin 12 Gene Therapy for Locally Recurrent Prostate Cancer

Study Overview
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Brief Summary
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The primary purpose of this phase 1 study is to determine the dose-dependent toxicity and maximum tolerated dose (MTD) of oncolytic adenovirus-mediated cytotoxic and IL-12 gene therapy in men with locally recurrent prostate cancer after definitive radiotherapy

Official Title
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Phase 1 Trial of Oncolytic Adenovirus-Mediated Cytotoxic and Interleukin 12 Gene Therapy for Locally Recurrent Prostate Cancer After Definitive Radiotherapy

Conditions
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Prostate Cancer

Intervention / Treatment
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* Biological: Ad5-yCD/mutTKSR39rep-hIL12


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Biopsy-proven local recurrence of prostate cancer at least one year after the completion of definitive radiation therapy Evidence of biologically active disease as demonstrated by an unequivocally rising serum PSA level that is ≥ 2 ng/mL above the nadir PSA < 100 ng/mL Age ≥ 18 years Karnofsky performance status ≥ 70 Negative lymph nodes as established by imaging (pelvic CT or pelvic MRI) No evidence of metastatic disease, as evaluated by bone scan and CT scan of the abdomen and pelvis. Subjects must have adequate baseline organ function as assessed by the the following laboratory values: Adequate renal function with serum creatinine ≤ 1.5 mg/dL Platelet count > 100,000/µL Absolute neutrophil count > 1,000/µL Hemoglobin > 10.0 g/dL Bilirubin > 1.5 mg/dL AST/SGOT and ALT/SGPT < 3.0 times upper limit of normal (ULN) Men of child-producing potential must be willing to consent to use effective contraception for at least 3 months after the gene therapy 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: PSA ≥ 100 ng/mL Prostate volume > 100 cc Pathologically positive lymph nodes or nodes > 1.0 cm on imaging (nodes > 1.0 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. Subjects must be disease-free for > 5 years Prior radical prostatectomy, cryosurgery for prostate cancer, or bilateral orchiectomy for any reason If the subject had prior androgen deprivation therapy (ADT), the subject exhibited biochemical failure while on ADT Prior systemic chemotherapy for the study cancer (prior chemotherapy for a different cancer is allowed; however, subjects must be > 2 years post-completion of chemotherapy at the time of registration. Subjects on Proscar therapy must stop to be eligible) Major surgery planned within 3 months of registration Severe, active co-morbidity defined as: New York Health Association Class II or greater congestive heart failure or active ventricular arrhythmia requiring medication Chronic obstructive pulmonary disease (COPD) exacerbation or other respiratory illness requiring hospitalization within last 3 months or precluding study therapy at the time of registration Acute infection 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 Ciproflaxin, another antibiotic can be substituted at the discretion of the treating physician Serious medical or psychiatric illness or concomitant medication, which, in the judgement of the principal investigator, might interfere with the subject's ability to respond to or tolerate the treatment or complete the trial

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single<br>Single intraprostatic injection of Ad5-yCD/mutTKSR39rep-hIL12 adenovirus at a dose of 1 x 10e10 to 1 x 10e12 viral particles. | Biological: Ad5-yCD/mutTKSR39rep-hIL12<br>* Single intraprostatic injection of Ad5-yCD/mutTKSR39rep-hIL12 on day 1<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-dependent toxicity and maximum tolerated dose (MTD) of adenovirus |  | 30 days from date of adenovirus injection (defined as day 1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PSA response |  | 2 years | 
| Freedom from biochemical/clinical failure (FFF) |  | 2 years | 
| PSA doubling time (PSADT) |  | 2 years | 
| Disease-specific and overall survival |  | 5 years | 
| Quality of life (QOL) |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prostate Cancer, Locally Recurrent, Gene Therapy, IL-12, Adenovirus