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

Prostate Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02555397
• Other study ID #: Prostate Cancer (9829)
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: August 2015
• Est. completion date: February 14, 2023

Study information

• Verified date: February 2022
• Source: Henry Ford Health System
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 15
• Est. completion date: February 14, 2023
• Est. primary completion date: June 16, 2019
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

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

Locations

Country	Name	City	State
United States	Henry Ford Health System	Detroit	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Henry Ford Health System

Country where clinical trial is conducted

United States, 

References & Publications (1)

Freytag SO, Barton KN, Zhang Y. Efficacy of oncolytic adenovirus expressing suicide genes and interleukin-12 in preclinical model of prostate cancer. Gene Ther. 2013 Dec;20(12):1131-9. doi: 10.1038/gt.2013.40. Epub 2013 Jul 11. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Primary	Dose-dependent toxicity and maximum tolerated dose (MTD) of adenovirus		30 days from date of adenovirus injection (defined as day 1)
Secondary	PSA response		2 years
Secondary	Freedom from biochemical/clinical failure (FFF)		2 years
Secondary	PSA doubling time (PSADT)		2 years
Secondary	Disease-specific and overall survival		5 years
Secondary	Quality of life (QOL)		2 years