AdUP: AdNRGM; VDEPT + GMCSF in locally recurrent prostate cancer

• Register: ISRCTN
• Last refreshed on: 13 June 2023
• Main ID: ISRCTN06254734
• Date of registration: 28/02/2013
• Prospective Registration: Yes
• Primary sponsor: University of Birmingham (UK)
• Public title: AdUP: AdNRGM; VDEPT + GMCSF in locally recurrent prostate cancer
• Scientific title: AdUP: A Phase I Clinical Trial of a replication defective type 5 adenovirus vector expressing nitroreductase and GMCSF (AdNRGM) given via trans-perineal, template-guided, intra-prostatic injection, followed by intravenous CB1954, in patients with locally relapsed hormone-refractory Prostate Cancer
• Date of first enrolment: 15/03/2013
• Target sample size: 15
• Recruitment status: Completed
• URL: https://www.isrctn.com/ISRCTN06254734
• Study type: Interventional
• Study design: Non-randomised interventional; Design type: Treatment (Treatment)
• Phase: Phase I

Countries of recruitment

England, United Kingdom

Contacts

• Name: Ann Pope

Key inclusion & exclusion criteria

Inclusion criteria: 1. Patients who present with biopsy proven local recurrence of prostate cancer following radical radiotherapy and a rising PSA while on androgen suppression with LHRH agonist therapy or after bilateral orchidectomy. A rising PSA is defined as 3 consecutive increases (measured by the same laboratory) over a minimum period of 6 weeks, with timepoints separated by at least 15 days. If the patient is on LHRH agonist therapy, this therapy should be continued.
2. Life expectancy greater than 3 months
3. Aged at least 18 years
4. Written informed consent
5. WHO performance status of 0-1 (Appendix 2)
6. PSA value = 4 and = 25 ng/ml at study entry
7. Adequate hepatic function (i.e. bilirubin, AST, ALT all < 1.5 x upper limit of normal for Institution)
8. Normal renal function (<1.25 x upper normal limit for the Institution)
9. Adequate haematological function (i.e. haemoglobin > 10g/dl, WCC > 3x109/l, platelets > 150x109/l) and normal clotting (INR and APTT <1.2)
10. Patients must agree not to father a child within 12 months following AdNRGM administration, and must practice a barrier method of contraception starting from the time of AdNRGM administration for at least 12 months
11. No known immunoincompetence
Exclusion criteria: 1. Patients with a prostate or tumour which is deemed clinically unsuitable for transperineal templateguided injection
2. Patients who have previously been treated with prostate brachytherapy
3. Patients who have received chemotherapy, radiotherapy or immunotherapy within 28 days of study entry
4. Acute active infection (viral, bacterial, or fungal) which requires specific therapy
5. Chronic hepatitis B or C infection, HIV positive patients (patients will be tested for HBV/HCV, but not HIV)
6. Concurrent severe medical illnesses incompatible with the treatment including psychiatric pathology likely to affect protocol compliance
7. Tumours of other organs or tissues still active or treated radically less that 3 years before (except that successfully treated, nonmetastatic skin cancers are not an exclusion criterion)
8. Concurrent corticosteroids, or any medication known to have significant immunosuppressive action
9. Patients unable to travel for regular hospital assessments
10. Evidence of adenovirus infection and/or shedding at prescreening

Age minimum:
Age maximum:
Gender: Male

Health Condition(s) or Problem(s) studied

Prostate cancer
Cancer
Malignant neoplasm of prostate

Intervention(s)

Current interventions as of 12/07/2016:
This is an open-label, non-randomised, phase I, sequential group trial which will explore the safety and tolerability of ascending doses of replication defective adenovirus type 5 vector expressing nitroreductase and GMCSF (AdNRGM), in combination with CB1954. Five groups of three patients each will be treated with escalating doses of AdNRGM (1010, 3x1010, 1011, 3x1011, 1012 vp) followed 2 days later by intravenous CB1954 at a fixed dose (24mg/m2). The AdNRGM is given via trans-perineal, template-guided, intra-prostatic injection. Patients will be monitored on days 1, 2 and 5-7 following AdNRGM administration, with telephone contact on days 3 and 4; then seen at weeks 2, 3 and 4, then monthly for 12 months or until PSA progression.

Previous interventions:
AdNRGM Administration, Template-guided prostate brachytherapy
CB1954 Infusion, Infusion of 24 mg/m2

Primary Outcome(s)

Current primary outcome measures as of 26/07/2016:
1. Safety and tolerability of escalating doses of AdNRGM, followed by iv CB1954 determined by assessing local effects on tumour etc. and number of participants with treatment related adverse events by CTCAE v4.0 (Time Frame: 12 months)
1.1. Safety will be assessed in terms of local effects on the tumour, the prostate gland and the lower urinary tract as well as in terms of systemic effects. The data will be summarised descriptively
1.2. Adverse events and side effects will be determined as changes of the relevant clinical parameters as well as changes of haematological and clinical biochemistry data

Previous primary outcome measures:
Toxicity; timepoint(s): up to end of Month 11 visit

Secondary Outcome(s)

Current secondary outcome measures as of 26/07/2016:
1. PSA levels and PSA kinetics following treatment with AdNRGM and CB1954 (time frame: 12 months). Changes in the level and kinetics of the serum PSA will be measured to provide an indication of changes in tumour burden, growth rate and possible anti-tumour activity of the treatment.

Other pre-specified outcome measures:
2. Evidence for local tumour destruction, and immune infiltration, in tumour biopsies taken after the treatment (time frame: 12 months). Treatment-induced immune responses will be assessed by measurement of T cell responses to prostate cancer antigens in blood samples collected at baseline and at intervals (2, 3, 4, and 8 weeks) following treatment.
3. Changes in cellular immune response to prostate cancer antigens following treatment with AdNRGM and CB1954 (time frame: 12 months). Evidence of tumour destruction and immune infiltration will be assessed by looking at patterns of tissue damage, residual tumour tissue and immune cell infiltrates detected by immunohistochemistry in post-treatment prostate biopsies

Previous secondary outcome measures:
PSA level and kinetics; timepoint(s): Up to end of Month 11

Secondary ID(s)

13599

2007-700341-13

NCT04374240

Source(s) of Monetary Support

Cancer Research UK (UK); Grant Codes: C198/A9699, Medical Research Council (MRC) (UK)

Ethics review

Status:
Approval date:
Contact:

Oxford A, 07/12/2012, ref: 12_SC_0660

Results

• Results available: Yes
• Date Completed: 31/07/2021