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

NCT02555397 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: Prostate Cancer (9829)
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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

Conditions

Prostate Cancer

Keywords

Prostate Cancer; Locally Recurrent; Gene Therapy; IL-12; Adenovirus

Outcome Measures

Primary Outcomes (1)

• Dose-dependent Toxicity

  30 days from date of adenovirus injection (defined as day 1)

Secondary Outcomes (5)

• 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 Outcomes (1)

• 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

Study Arms (1)

Single

EXPERIMENTAL

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

Interventions

Ad5-yCD/mutTKSR39rep-hIL12 BIOLOGICAL

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

Single

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Henry Ford Health System: lead

Study Sites (1)

Henry Ford Health System

Detroit, Michigan, 40202, United States

Location

Related Publications (2)

• 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.

  PMID: 23842593 BACKGROUND

• Nyati S, Stricker H, Barton KN, Li P, Elshaikh M, Ali H, Brown SL, Hwang C, Peabody J, Freytag SO, Movsas B, Siddiqui F. A phase I clinical trial of oncolytic adenovirus mediated suicide and interleukin-12 gene therapy in patients with recurrent localized prostate adenocarcinoma. PLoS One. 2023 Sep 15;18(9):e0291315. doi: 10.1371/journal.pone.0291315. eCollection 2023.

  PMID: 37713401 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms; Adenoviridae Infections

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; DNA Virus Infections; Virus Diseases; Infections

Results Point of Contact

• Title: Shyam Nyati
• Organization: Henry Ford Health System

snyati1@hfhs.org

734-272-1751

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Staff Physician

Study Record Dates

• First Submitted: September 17, 2015
• First Posted: September 21, 2015
• Study Start: August 1, 2015
• Primary Completion: June 16, 2019
• Study Completion: January 22, 2024
• Last Updated: October 10, 2024
• Results First Posted: October 10, 2024

Record last verified: 2024-07

Locations

US (1)