E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
advanced metastatic castration-resistant prostate cancer |
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E.1.1.1 | Medical condition in easily understood language |
metastatic prostate cancer |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10036909 |
E.1.2 | Term | Prostate cancer metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this clinical trial is to evaluate the safety of the combination of DCVAC/PCa with ONCOS-102 primed with cyclophosphamide (CPO) in men with castration-resistant advanced metastatic prostate cancer, who have progressed following initial therapy with either hormonal manipulation (eg,abiraerone and enzalutamide) or chemotherapy |
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E.2.2 | Secondary objectives of the trial |
• To evaluate time to disease progression demonstrated by prostate-specific antigen (PSA) levels
• To evaluate radiographic progression-free survival by radiographic evidence of disease progression per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1
• To evaluate overall survival
• To evaluate the objective response rate
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Males 18 years of age and older
2. Histologically or cytologically confirmed adenocarcinoma of the prostate
3. Radiographically documented metastatic disease (presence of skeletal or soft-tissue/visceral/nodal metastases) with evidence of disease according to the following criteria:
- Measurable lymph nodes (short axis ≥ 15 mm) or visceral lesion measurable per RECIST v 1.1 or
- Two or more lesions on bone scan/imaging and with at least one soft tissue or visceral lesion being accessible for intratumoral administration of ONCOS-102 and biopsy.
4. ECOG performance status 0-1
5. PSA ≥2 ng/mL
6. Rising PSA levels after previous treatment failure.
7. Surgically or medically castrate with serum testosterone levels ≤1.7 nmol/L. Patients who have not had bilateral orchiectomy must be maintained on standard dosing of GnRH/LHRH analog therapy at appropriate frequency for the duration of the clinical trial.
8. Laboratory criteria:
a. White blood cell count (WBC) greater than 4,000/mm3 (4.0×109/L)
b. Platelet count of at least 100,000/mm3 (100×109/L)
c. Total bilirubin within normal limits (benign hereditary hyper-bilirubinemias, eg, Gilbert’s syndrome, are permitted)*
d. Serum alanine aminotransferase, aspartate aminotransferase, and creatinine <1.5×ULN *
*If the patient has liver metastases, these parameters might not be applicable and the decision on inclusion of the patient into the study is to be made by the Investigator after discussion with the Sponsor’s Medical Monitor.
9. Patients who have progressed following:
a. at least initial therapy (chemotherapy or treatment with a hormonal agent known to impact survival such as abiraterone and enzalutamide); or
b. one first-line chemotherapy regimen and one additional hormonal agent known to impact survival such as abiraterone and enzalutamide; or
c. failure of two lines of chemotherapy; or
d. failure of pre-chemotherapy abiraterone or enzalutamide and subsequent chemotherapy
10. Life expectancy of at least 12 months based on the Investigator’s judgement
11. Signed Informed Consent Form |
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E.4 | Principal exclusion criteria |
1. Patients with neuroendocrine or small cell cancer of the prostate
2. History of other malignant disease (with the exception of the primary prostate cancer and non-melanoma skin tumors) in the past 5 years
3. Systemic immunosuppressive therapy apart from corticosteroids at a dose of less than 10 mg/day
4. Administration of experimental therapy within the last 4 weeks before start of screening
5. Treatment with immunotherapy within the last 3 months before start of screening
6. Treatment with radiopharmaceutical drugs within 8 weeks before start of screening
7. Patient significant co-morbidities (cardiovascular diseases, eg, unstable angina pectoris, uncontrolled hypertension, myocardial infarction, ventricular arrhythmia, or stroke within a 6-month period before the Baseline visit; congestive heart failure or cardiac arrhythmia not controlled by treatment; active severe infections; uncontrolled metabolic disorders; etc.)
8. Known hypersensitivity or allergic reaction (other than local inflammatory reaction or irritation at injection site) to DCVAC/PCa or its constituents, ie, CryoStor CS10 freeze medium (Biolife Solutions) containing 10% dimethyl sulfoxide
9. Uncontrolled co-morbidities including social conditions which in the Investigator’s opinion would prevent participation in/completion of the clinical trial
10. Patients known to be HIV positive or syphilitic
11. Known active (infectious) hepatitis B and active hepatitis C
12. Known central nervous malignancies such as glioma and brain metastases
13. Receipt of oncolytic virus treatment or vaccination with a live virus within 4 weeks of study start
14. History of organ transplantation
15. Any autoimmune diseases, therapies with monoclonal antibodies, any psychiatric disease, medical history of active TBC and any allogeneic stem cell transplantations in the last 5 years |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety profile as measured by adverse events (AEs), serious adverse events (SAEs), laboratory abnormalities, and vital signs
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
after the last visit of the last patient enrolled in the clinical trial. |
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E.5.2 | Secondary end point(s) |
• Time to PSA progression demonstrated by a rising PSA value as defined by the Prostate Cancer Working Group 2, ie, 25% or greater increase and an absolute increase of 2 ng/mL or more from the nadir, which is confirmed by a second value (also 25% or greater increase and an absolute increase of 2 ng/mL or more from the nadir) obtained 3 to 6 weeks later
• Radiographic progression-free survival (per RECIST v 1.1), a composite of:
o radiographic progression of bone lesions
o radiographic progression of soft tissue lesions
o death due to any cause
• Overall survival
• Objective response rate (per RECIST v 1.1)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
after the last visit of the last patient enrolled in the clinical trial. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |