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

Sponsor

Henry Ford Health System (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02555397

Collaborator

(none)

Enrollment

Location

Arm

90.5

Anticipated Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Biological: Ad5-yCD/mutTKSR39rep-hIL12	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

15 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Aug 1, 2015

Actual Primary Completion Date :

Jun 16, 2019

Anticipated Study Completion Date :

Feb 14, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Single 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 Single intraprostatic injection of Ad5-yCD/mutTKSR39rep-hIL12 on day 1

Arm

Intervention/Treatment

Experimental: Single

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

Single intraprostatic injection of Ad5-yCD/mutTKSR39rep-hIL12 on day 1

Outcome Measures

Primary Outcome Measures

Dose-dependent toxicity and maximum tolerated dose (MTD) of adenovirus [30 days from date of adenovirus injection (defined as day 1)]

Secondary Outcome Measures

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]

Other Outcome Measures

Association between the primary and secondary outcomes and immunological endpoints including serum IL-12 and IFN-y levels and NK cell cytolytic activity [3 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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