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

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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Biological: Ad5-yCD/mutTKSR39rep-hIL12

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Detroit, Michigan, United States, 40202
      • Henry Ford Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Other Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Henry Ford Health System

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2015
• Primary Completion (Actual): June 16, 2019
• Study Completion (Anticipated): February 14, 2023

Study Registration Dates

• First Submitted: September 17, 2015
• First Submitted That Met QC Criteria: September 17, 2015
• First Posted (Estimate): September 21, 2015

Study Record Updates

• Last Update Posted (Actual): March 3, 2022
• Last Update Submitted That Met QC Criteria: February 17, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Gene Therapy; Prostate Cancer; Adenovirus; Locally Recurrent; IL-12
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: Prostate Cancer (9829)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No