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A Clinical Trial of AdNRGM Plus CB1954 in Prostate Cancer (AdUP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT04374240
Recruitment Status : Active, not recruiting
First Posted : May 5, 2020
Last Update Posted : January 19, 2021
Janssen, LP
Department of Health, United Kingdom
Medical Research Council
Information provided by (Responsible Party):
University of Birmingham

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Prostate Cancer Genetic: AdNRGM Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: AdNRGM plus CB1954
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : March 19, 2013
Estimated Primary Completion Date : April 2021
Estimated Study Completion Date : April 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: AdNRGM followed on day 2 by CB1954
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
Genetic: AdNRGM

AdNRGM is an E1-E3 deleted, replication deficient type 5 adenovirus which contains the E. coli NTR gene regulated by the CMV promoter, an internal ribosomal entry site (IRES) and the human GMCSF gene.

CB1954 [5-(aziridin-1-yl)-2,4-dinitrobenzamide]

Other Name: CB1954

Primary Outcome Measures :
  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 ]
    • 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 Outcome Measures :
  1. Measuring PSA levels following treatment with AdNRGM and CB1954 [ Time Frame: 12 months ]
    Changes in the level (ng/ml) of the serum PSA will be measured in to provide an indication of changes in tumour burden, growth rate and possible anti-tumour activity of the treatment.

Other Outcome Measures:
  1. To assess the evidence for local tumour destruction, and immune infiltration, in tumour biopsies taken after the treatment [ Time Frame: 8 weeks post treatment ]
    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.

  2. To investigate 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 .

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04374240

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United Kingdom
Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust
Birmingham, West Midlands, United Kingdom, B15 2GW
Sponsors and Collaborators
University of Birmingham
Janssen, LP
Department of Health, United Kingdom
Medical Research Council
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Principal Investigator: Prashant Patel, FRCS Ed University of Birmingham
Additional Information:
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Responsible Party: University of Birmingham Identifier: NCT04374240    
Other Study ID Numbers: RG_06-226
ISRCTN06254734 ( Registry Identifier: ISRCTN )
2007-007041-13 ( EudraCT Number )
First Posted: May 5, 2020    Key Record Dates
Last Update Posted: January 19, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by University of Birmingham:
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Prostatic Diseases
Antineoplastic Agents