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

• ClinicalTrials.gov Identifier: NCT02555397
• Recruitment Status: Active, not recruiting
• First Posted: September 21, 2015
• Last Update Posted: March 3, 2022
• Sponsor: Henry Ford Health System
• Information provided by (Responsible Party): Farzan Siddiqui, Henry Ford Health System

Tracking Information

• First Submitted Date: September 17, 2015
• First Posted Date: September 21, 2015
• Last Update Posted Date: March 3, 2022
• Actual Study Start Date: August 2015
• Actual Primary Completion Date: June 16, 2019 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: September 17, 2015): Dose-dependent toxicity and maximum tolerated dose (MTD) of adenovirus [ Time Frame: 30 days from date of adenovirus injection (defined as day 1) ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 17, 2015)

• PSA response [ Time Frame: 2 years ]
• Freedom from biochemical/clinical failure (FFF) [ Time Frame: 2 years ]
• PSA doubling time (PSADT) [ Time Frame: 2 years ]
• Disease-specific and overall survival [ Time Frame: 5 years ]
• Quality of life (QOL) [ Time Frame: 2 years ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures (submitted: September 17, 2015): Association between the primary and secondary outcomes and immunological endpoints including serum IL-12 and IFN-y levels and NK cell cytolytic activity [ Time Frame: 3 months ]
• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Phase 1 Trial of Interleukin 12 Gene Therapy for Locally Recurrent Prostate Cancer
• Official Title: Phase 1 Trial of Oncolytic Adenovirus-Mediated Cytotoxic and Interleukin 12 Gene Therapy for Locally Recurrent Prostate Cancer After Definitive Radiotherapy
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Prostate Cancer

Intervention

Biological: Ad5-yCD/mutTKSR39rep-hIL12

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

Study Arms

Experimental: Single

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

Intervention: Biological: Ad5-yCD/mutTKSR39rep-hIL12

• 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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: September 17, 2015): 15
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: February 14, 2023
• Actual Primary Completion Date: June 16, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02555397
• Other Study ID Numbers: Prostate Cancer (9829)
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Farzan Siddiqui, Henry Ford Health System
• Original Responsible Party: Hans Stricker, MD, Henry Ford Health System, Vice Chair - Urology
• Current Study Sponsor: Henry Ford Health System
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Henry Ford Health System
• Verification Date: February 2022