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

Phase 1

Completed

Conditions: Prostate Cancer

Interventions: Biological: Ad5-yCD/mutTKSR39rep-hIL12

Registration Number: NCT02555397

Lead Sponsor: Henry Ford Health System

Brief Summary: 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

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 15

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Single	Ad5-yCD/mutTKSR39rep-hIL12	Single intraprostatic injection of Ad5-yCD/mutTKSR39rep-hIL12 adenovirus at a dose of 1 x 10e10 to 1 x 10e12 viral particles.

Primary Outcome Measures

Name	Time	Method
Dose-dependent Toxicity	30 days from date of adenovirus injection (defined as day 1)

Secondary Outcome Measures

Name	Time	Method
Quality of Life (QOL)	2 years
PSA Doubling Time (PSADT)	2 years
Disease-specific and Overall Survival	5 years
PSA Response	2 years
Freedom From Biochemical/Clinical Failure (FFF)	2 years