None listed
Conditions
Brief summary
The purpose of this study is to learn whether injecting Pexa-Vec directly into the prostate cancer or into the blood stream is a safe and useful treatment for patients with prostate cancer, before they undergo standard surgery to remove the prostate gland. Who is it for? You may be eligible for this study if you are aged 18 years or older, have been recently diagnosed with prostate cancer and you haven't received any previous cancer treatments, including surgery, androgen deprivation therapy, chemotherapy or radiotherapy. Study details Participants in this study will have a small sample of prostate tissue (biopsy) taken before they receive any treatment. The first 10 participants will have a single dose of Pexa-Vec modified viral treatment injected directly into their prostate gland while they are in an MRI scanner, at least 4 weeks prior to prostate removal surgery. The second 10 participants will have two doses of Pexa-Vec treatment injected directly into their prostrate gland while they are in an MRI scanner, the first dose will be 6 weeks prior to surgery and the second dose at least 4 weeks prior to surgery. The last 10 participants will have two doses of Pexa-Vec treatment injected into their blood stream, the first dose will be at least 5 weeks prior to surgery and the second dose at least 4 weeks prior to surgery. All participants will undergo prostate removal surgery as scheduled by their doctor and will be asked to attend a series of follow-up appointments for up to 90 days after surgery to discuss their health and any complications they might have had. It is hoped this research may be used to improve health outcomes for future patients with prostate cancer by determining whether Pexa-Vec is safe and effective at changing the appearance of tumour and immune cells, while possibly reducing tumour cell growth prior to prostate removal surgery.
Interventions
Arm 1: MRI-guided intratumoural (IT) Pexastimogene Devacirepvec (Pexa-Vec) (1x109 PFU) x 1 dose (Day 1). Radical prostatectomy will be performed 29-43 days following the IT injection. The MRI-guided injection will be performed by a specialised radiologist with previous experience and training in this procedure. Overall study duration for participants in this arm is 119-133 days.
Arm 2: MRI-guided intratumoural Pexastimogene Devacirepvec (Pexa-Vec) (1x109 PFU) x 2 doses (Day 1, 15). Radical pro
Arm 1: MRI-guided intratumoural (IT) Pexastimogene Devacirepvec (Pexa-Vec) (1x109 PFU) x 1 dose (Day 1). Radical prostatectomy will be performed 29-43 days following the IT injection. The MRI-guided injection will be performed by a specialised radiologist with previous experience and training in this procedure. Overall study duration for participants in this arm is 119-133 days. Arm 2: MRI-guided intratumoural Pexastimogene Devacirepvec (Pexa-Vec) (1x109 PFU) x 2 doses (Day 1, 15). Radical prostatectomy will be performed 43-57 days after the first IT injection. The MRI-guided injection will be performed by a specialised radiologist with previous experience and training in this procedure. Overall study duration for participants in this arm is 133 - 147 days. Arm 3: Systemic intravenous (IV) infusion Pexastimogene Devacirepvec (Pexa-Vec) (1x109 PFU) x 2 doses (Day 1, 8). The IV infusion will be performed by a medical oncologist and clinical research coordinator. Radical prostatectomy will be performed 36-50 days after the first IV infusion. Overall study duration for participants in this arm is 126-140 days. For all arms of the study adherence to the intervention will be monitored by the Data and Safety Monitoring Committee and central medical review of source documents. Laboratory tests and clinical reviews will be performed 7 days after each treatment.
Sponsors
Royal Melbourne Hospital
Study design
Allocation
Non-randomised trial
Intervention model
Other
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
Male
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patient has provided written informed consent 2. Patients with histologically confirmed prostate adenocarcinoma 3. Age greater than or equal to 18 years 4. Suitable for radical prostatectomy in the opinion of the treating surgeon, following results of all screening investigations, including PSMA PET/CT scan 5. Disease detectable on MRI 6. Patient has adequate organ function within 7 days prior to registration as defined as: White blood cell count (WCC) greater than or equal to 2 x 109/L Absolute neutrophil count (ANC) greater than or equal to 1 x 109/L Haemoglobin greater than or equal to 90 g/L Platelet count greater than or equal to 100 x 109/L Activated partial thromboplastin time (aPTT) less than or equal to 1.5 ULN International Normalized Ratio (INR) less than or equal to 1.5 ULN Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 2.5 x ULN unless liver metastases are present, in which case it must be less than or equal to 5 x ULN Serum sodium 130-150mmol/L Serum potassium 3.0-5.5mmol/L Serum Corrected Calcium 2.0-2.9 mmol/L Serum Creatinine less than or equal to 1.5 ULN or estimated glomerular filtration rate greater than 30mL/min/1.73m2 Oxygen saturation (SaO2) by pulse oximetry greater than 90% at rest 7. For patients who are sexually active with partners of childbearing potential: willing to use double barrier contraception method for at least 6 weeks after each treatment of Pexa-Vec 8. Willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations during both the treatment and follow-up phases
Exclusion criteria
1. Prior anti-cancer therapy for prostate cancer 2. High volume metastatic disease on imaging including PSMA PET/CT as defined by one or more of the following criteria: a. The presence of visceral metastases b. greater than or equal to 4 bone lesions, including greater than or equal to 1 beyond the vertebral bodies and pelvis 3. Low-risk prostate cancer as defined by all of the following criteria a. PSA < 20ng/ml b. Gleason score 3+4=7 or equal to or less than 6 c. Clinor equal toical stage < T2c 4. Known immunodeficiency due to underlying illness (e.g., human immunodeficiency virus [HIV] / acquired immune deficiency syndrome [AIDS]) and/or long-term immune-suppressive medication including high-dose corticosteroids (defined as >10 mg/day prednisone or equivalent) 5. Known myeloproliferative disorders requiring systemic therapy 6. History of severe inflammatory or exfoliative skin condition (e.g. eczema or ectopic dermatitis) requiring systemic therapy 7. Tumour in location that would potentially result in significant clinical adverse effects if post-treatment tumour swelling were to occur 8. Tumour invading a major vascular structure or other key anatomical structure 9. Severe or unstable cardiovascular disease, including but not limited to significant coronary artery disease (e.g., myocardial infarction or other coronary artery disease requiring angioplasty or stenting) or congestive heart failure within the preceding 12 months 10. Inability to suspend treatment with anti-hypertensive medication (including but not limited to: diuretics, beta-blockers, angiotensin converting enzyme [ACE] inhibitors, aldosterone antagonists, etc.) for 48 hours prior to and 48 hours after all Pexa-Vec treatments 11. Use of anti-viral medications 12. Use of anti-platelet, or anti-coagulation medication that cannot be safely suspended prior to IT injections 13. Medical conditions that place the patient at risk should tachycardia, hypotension or volume loading occur during or following treatment with Pexa-Vec 14. Experienced a severe systemic reaction or side-effect as a result of a previous smallpox vaccination 15. Other medical condition or laboratory abnormality or active infection that in the judgment of the Investigator may increase the risk associated with study participation or may interfere with interpretation of study results and/or otherwise make the patient inappropriate for entry into this study 16. Prior malignancy except for cancer from which the patient has been disease-free for 3 years, or the following: adequately treated basal or squamous cell skin cancer, in situ carcinoma (including cervical, breast and superficial bladder cancer) 17. Prior or planned organ transplant 18. Use of interferon/pegylated interferon (PEG-IFN) or ribavirin that cannot be discontinued within 14 days prior to any Pexa-Vec dose 19. Known active Hepatitis B or Hepatitis C 20. Patients must not receive live vaccines, other than Pexa-Vec, within 30 days of planned start of Pexa-Vec, during the study, and for a minimum of 15 weeks after the last dose of Pexa-Vec 21. Clinically significant and/or rapidly accumulating ascites, pericardial and/or pleural effusions 22. Inability to avoid direct physical contact with household contacts who are at high risk if exposed to Pexa-Vec. High risk patients include any of the following: a. pregnant or breastfeeding women b. children <12 months of age c. immunocompromised individuals (e.g., organ transplant recipients, HIV-positive individuals, or those receiving chronic immunosuppressive medication) d. individuals with ongoing severe inflammatory skin condition requiring medical treatment or history of severe eczema requiring medical treatment
Outcome results
None listed