Clinical trial · Interventional
A Clinical Trial of AdNRGM Plus CB1954 in Prostate Cancer
Phase I Trial of Replicative Defective Type 5 Adenovirus Vector Expressing Nitroreductase & GMCSF Given Via Trans-perineal Template-guided Intra-prostatic Injection Followed by iv CB1954 in Locally Relapsed Prostate Cancer Patients
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
This is an open label, non-randomised, phase I, sequential group trial which will explore the safety and tolerability of ascending doses of AdNRGM, in combination with CB1954. Five groups of 3 patients each will be treated with escalating doses of AdNRGM (10\^10, 3x10\^10, 10\^11, 3x10\^11, 10\^12 vp) followed 2 days later by intravenous CB1954 at a fixed dose (24mg/m\^2). To ensure the coverage of the whole prostate the vector will be delivered by multiple, template-guided trans-perineal injections using an adaptation of standard prostate brachytherapy technique. Dose escalation will be dependent on safety and tolerability; at each dose-level, if dose-limiting toxicity (DLT) is seen in one patient, the cohort will be expanded to a maximum of 6 patients. If DLT is then observed in a second patient at that dose, no further patients will be recruited and the previous (lower) dose-level will be defined as the maximum tolerated dose (MTD). If DLT is seen in 0/3 or just 1/6 patients, dose escalation may continue.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Prostate Cancer | Malignant Prostate Neoplasm | CURATED_EXACT | 0.92 |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| AdNRGM | Genetic | — | UNRESOLVED |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- AdNRGM followed on day 2 by CB1954
- description
- The proposed dose levels for AdNRGM are 10\^10, 3x10\^10, 10\^11, 3x10\^11, 10\^12 vp while the prodrug CB1954 will be given at a standard dose of 24 mg/m\^2
- interventionNames
- Genetic: AdNRGM
Primary outcomes (1)
- measure
- 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
- timeFrame
- 12 months
- description
- * 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. * 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.
Secondary outcomes (1)
Eligibility
Eligibility (as posted)
- Sex
- Male
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: * Patients who present with biopsy-proven local recurrence of prostate cancer following radical radiotherapy and a rising PSA with or without androgen suppression with antiandrogens or LHRH agonist/antagonist therapy or after bilateral orchidectomy. A rising PSA is defined as 2 increases over 3 or 4 readings over a minimum period of 6 weeks, with time-points separated by at least 2 weeks. If the patient is on antiandrogens or LHRH agonist/antagonist therapy, this therapy should be continued. * Life expectancy greater than 3 months. * Aged at least 18 years. * Written informed consent. * World Health Organisation (WHO) performance status of 0-1. * PSA value ≥ 2 and ≤ 100 ng/ml at study entry. * Adequate hepatic function (i.e. bilirubin, AST, ALT all \< 1.5 x upper limit of normal for Institution). * Normal renal function (\<1.25 x upper normal limit for the Institution). * Adequate haematological function (i.e. haemoglobin \> 10g/dl, WCC \> 3x109/l, platelets \> 150x10\^9/l) and normal clotting (INR and APTT \<1.2). * Patients must agree not to father a child within 12 months following AdNRGM administration, and must use at least two methods of contraception, one of which is barrier, starting from the time of AdNRGM administration for at least 12 months. * No known immuno-incompetence. Exclusion Criteria: * Patients with a prostate or abnormal focus which is deemed clinically unsuitable for trans-perineal template-guided injection. * Patients who have previously been treated with prostate brachytherapy. * Patients who have previously been treated with AdNRGM and CB1954; or who have been administered any other human adenovirus type 5 vector within the last 5 years. * Patients who have received chemotherapy, radiotherapy or immunotherapy within 28 days of study entry. * Acute active infection (viral, bacterial, or fungal) which requires specific therapy. * Chronic hepatitis B or C infection, HIV positive patients. (Patients will be tested for HBV/HCV, but not HIV). * Concurrent severe medical illnesses incompatible with the treatment including psychiatric pathology likely to affect protocol compliance. * Tumours of other organs or tissues of high malignant potential still active or treated radically less than 3 years before (except that successfully treated, non-metastatic skin cancers or non-muscle invasive bladder cancers are not an exclusion criterion). * Concurrent corticosteroids, or any medication known to have significant immunosuppressive action. * Patients unable to travel for regular hospital assessments. * Evidence of adenovirus infection and/or shedding at baseline. * Clinical judgement by the Investigator that the patient should not participate in the study.
References
Publications (1)
- BACKGROUNDPatel P, Young JG, Mautner V, Ashdown D, Bonney S, Pineda RG, Collins SI, Searle PF, Hull D, Peers E, Chester J, Wallace DM, Doherty A, Leung H, Young LS, James ND. A phase I/II clinical trial in localized prostate cancer of an adenovirus expressing nitroreductase with CB1954 [correction of CB1984]. Mol Ther. 2009 Jul;17(7):1292-9. doi: 10.1038/mt.2009.80. Epub 2009 Apr 14. PMID 19367257