A Biomarker Study in Men With Localized Prostate Cancer Treated With Aglatimagene Besadenovec

Official title

A Biomarker Study in Men With Localized, Favorable, Intermediate-risk Prostate Cancer Treated With Aglatimagene Besadenovec

Overview

Phase 2a, open-label, multi-center study evaluating biomarkers and biodistribution of aglatimagene besadenovec plus valacyclovir in men with localized, intermediate-risk prostate cancer who are planning to receive external beam radiation therapy (EBRT).

Detailed description

This is a phase 2a, open-label, multi-center study evaluating aglatimagene besadenovec plus prodrug in men with localized, intermediate-risk prostate cancer who are planning to receive external beam radiation therapy (EBRT). Aglatimagene besadenovec is a replication-deficient adenoviral vector encoding the herpes simplex virus thymidine kinase (HSV-tk) gene. When combined with an oral antiviral prodrug (valacyclovir), this approach induces targeted tumor cell death and stimulates a systemic immune response. The study aims to characterize:

* Viral shedding and biodistribution of CAN-2409 genomes in blood, urine, and semen using validated qPCR assays. * Immune activation biomarkers, including lymphocyte subsets, cytokine profiles, and circulating tumor-related proteins.

Approximately 30 patients with intermediate risk prostate cancer will be recruited to the treatment arm and receive 3 courses of aglatimigene besadenovec by intraprostatic injection followed by orally administered valacyclovir. EBRT will start following the second injection. Biospecimens (blood, urine, semen) will be collected at specifed timepoints before and after each injection to assess biodistribution and immune response.

Approzimately 15 patients with intermediate risk prostate cancer will be recruited to the control arm receiving EBRT alone. Biospecimens (blood, urine, semen) will be collected at specified timepoints to assess immune response.

Safety will be monitored continuously. Frequency of treatment-emergent adverse events (TEAEs) and laboratory values will be evaluated for patients in the treatment arm. Patients in the control arm will be monitored for treatment-emergent serious adverse events suspected to be related to the collection of biospecimens.

Interventions

• Biological aglatimagene besadenovec + valacyclovir
  aglatimagene besadenovec: a genetically modified replication-defective adenoviral vector expressing the herpes simplex virus (HSV) thymidine kinase (tk) gene. Patients in the treatment arm will receive 3 intraprostatic injections of aglatimagene besadenovec, with each injection followed by a 14-day course of valacyclovir. Patients will have aglatimagene besadenovec administered either transrectally or transperineally.
• Radiation External Beam Radiation Therapy (EBRT)
  Standard of care standard or moderately hypofractionated prostate-only external beam radiation therapy (EBRT)

Primary outcome measures

• Biodistribution of aglatimagene besadenovec [Time frame: Up to 3 months post last injection of aglatimagene besadenovec.]

Secondary outcome measures (4)

• Biomarkers of immune activation and tumor burden [Time frame: Up to 3 months post last injection of aglatimagene besadenovec.]
• Biomarkers of immune activation and tumor burden [Time frame: Up to 3 months post last injection of aglatimagene besadenovec.]
• Biomarkers of immune activation and tumor burden [Time frame: Up to 3 months post last injection of aglatimagene besadenovec.]
• Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) [Time frame: Up to 3 months post last injection of aglatimagene besadenovec.]

Eligibility criteria

Inclusion criteria

• Participants must give study-specific informed consent prior to enrollment
• Histologically confirmed adenocarcinoma of the prostate
• Participants meeting National Comprehensive Cancer Network (NCCN) intermediate-risk criteria
• Participants must be planning and medically able to undergo standard or moderate hypofractionated prostate-only EBRT (treatment and control group) and able to tolerate multiple transrectal ultrasound guided injections (treatment group only)
• 18 years of age or older
• Performance status must be Eastern Cooperative Oncology Group 0-2
• The following laboratory criteria must be met (treatment group only):

• Aspartate aminotransferase (AST) < 3 x upper limit of normal
• Serum creatinine < 2 mg/dL
• Calculated creatinine clearance > 30 mL/min
• White blood cells > 3000/mm3
• Platelets >100,000/mm3

Exclusion criteria

• Active liver disease, including known cirrhosis or active hepatitis
• Participants on systemic corticosteroids (> 10 mg prednisone per day) or other immunosuppressive drugs
• Known HIV+ participants
• Regional lymph node involvement or distant metastases
• Participants planning to receive whole pelvic irradiation
• Other current malignancy (except squamous or basal cell skin cancers)
• Other serious co-morbid illness or compromised organ function that, in the opinion of the Investigator, would interfere with treatment or follow-up. For example, participants with diseases that preclude radiation therapy to the prostate such as severe prostatitis and inflammatory bowel disease.
• Prior treatment for prostate cancer except transurethral resection of the prostate (TURP). If prior TURP, participants must be deemed able to receive multiple intra-prostatic injections by the Investigator.
• Participants who had or plan to have orchiectomy as the form of hormonal ablation
• Known sensitivity or allergic reactions to acyclovir or valacyclovir (treatment group only)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Basic science

Study locations

United States · 7 centers

• Academic Urology and Urogynecology of Arizona — Peoria
• Colorado Clinical Research — Lakewood
• Urology Associates — Littleton
• Chesapeake Urology Research Associates — Towson
• Sheldon Freedman, MD Ltd. — Las Vegas
• Summit Health — Saddle Brook
• START Carolinas — Myrtle Beach

Identifiers

NCT: NCT07332000 · PrTK05

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗