E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Castration-resistant prostate cancer (patients who have achieved response to first-line docetaxel chemotherapy). |
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E.1.1.1 | Medical condition in easily understood language |
Castration-resistant prostate cancer (patients who have achieved response to first-line docetaxel chemotherapy). |
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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 | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10062904 |
E.1.2 | Term | Hormone-refractory prostate cancer |
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 |
To compare three different GX301 administration regimens in castration-resistant prostate cancer patients who have responded to first-line docetaxel, for the following co-primary outcomes:
• efficacy in inducing vaccine-specific immunological responses over a period of 6 months following randomisation;
• treatment safety and tolerability over the same period. |
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E.2.2 | Secondary objectives of the trial |
• To compare the three GX301 regimens for the following secondary outcomes:
- time-course of serum PSA;
- progression-free survival (censored at 18 months from randomisation);
- overall survival (censored at 24 months);
- treatment safety and tolerability beyond 6 months from randomisation.
• To investigate whether achievement of immunological response, irrespective of the assigned GX301 regimen, is related to progression-free and/or overall survival. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patient history
Eligible patients will have a documented history of the following:
Histologically confirmed diagnosis of prostate cancer, with an available Gleason score.
Diagnosis of progressive, castration-resistant prostate cancer (CRPC), leading to inception of first-line chemotherapy with a docetaxel-based regimen.
CRPC is defined as progression in PSA levels and/or in bone lesions or soft-tissue (visceral, nodal) lesions that has occurred during therapy with: front-line concurrent LHRH agonist and anti-androgen (maximal androgen blockade); or an anti-androgen added to front-line LHRH agonist following failure of the latter; or an LHRH-agonist replacing, or added to, front-line anti-androgen following failure of the latter.
Progression must have been observed: in all cases, in the presence of castrate serum testosterone levels (≤50 ng/dL or 1.7 nmol/L); in patients receiving anti-androgen therapy, following 6 or more weeks from discontinuation of the anti-androgen agent.
Completion of chemotherapy with a cumulative delivered dose of 300 to 825 mg/m2 docetaxel.
Current patient status
Age ≥18 years.
Ability to understand study-related patient information and provision of written informed consent for participation in the study.
Symptomatic or asymptomatic status (as for cancer-related symptoms).
ECOG performance status of 0 or 1.
Life expectancy of at least 6 months.
An interval ≥4 weeks elapsed from the last docetaxel administration.
Documented response to docetaxel chemotherapy. This is defined as post-chemotherapy PSA and imaging findings showing all of the following, as compared with the pre-chemotherapy documentation:
a) a PSA decrease ≥50% confirmed in two consecutive determinations obtained approximately 4 weeks apart;
b) absence of new bone lesions at radionuclide bone scan;
c) a status of soft-tissue (nodal, visceral) lesions meeting RECIST criteria for complete response or partial response.
Current castrate testosterone level (≤50 ng/dL or 1.7 nmol/L) due to current GnRH agonist or antagonist therapy or past orchiectomy.
Withdrawal of antiandrogen therapy, if any, for at least 4 weeks prior to randomization.
Haematology and blood chemistry values (central laboratory) complying with the following criteria:
- Total WBC count 3.0x109/L (to ensure that of a sufficient number of lymphocytes are available for the immunological tests)
- Platelets 100x109/L
- Serum bilirubin 1.5 times the upper normal limit (UNL)
- Alkaline phosphatase 3.0 times the UNL
- AST and ALT 2.5 times the UNL
- Creatinine 1.5 mg/dL (133 μmol/L).
Successful recovery from all acute toxicities from prior chemotherapy (except alopecia, grade 2 peripheral neuropathy and change in nails).
Confirmation from the immunology laboratory that the blood sample provided for baseline immunological tests is technically adequate. |
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E.4 | Principal exclusion criteria |
Known intolerance to Montanide or imiquimod. Montanide adjuvants are found as ingredients of experimental human vaccines. Imiquimod is the active ingredient of Aldara, a medicinal product for topical use.
Known presence of brain metastatic disease or spinal cord compression.
Radiotherapy within the past 4 weeks.
Concomitant presence of other primary malignancy except for non-melanomatous skin cancer, unless it was diagnosed and successfully treated ≥ 5 years ago with no subsequent evidence of recurrence.
Major surgery within 4 weeks prior to randomisation.
Cardiovascular illness or complication which, in Investigator’s judgment, compromises prognosis at 6 months or prevents the patient from following study procedures, including a recent history of stroke or myocardial infarction or presence of NYHA class III-IV heart failure or severe arrhythmia.
Serious (NCI CTCAE grade 3-4) uncontrolled infection.
Known presence of active autoimmune disease (e.g. rheumatoid arthritis, systemic lupus erythematosus, ulcerative colitis, Crohn's Disease, multiple sclerosis, ankylosing spondylitis).
Known presence of acquired, hereditary, or congenital immunodeficiency, (e.g. cellular immunodeficiencies, hypogammaglobulinemia, dysgammaglobulinemia).
HIV infection.
Current need for immunosuppressive drug therapy, including systemic corticosteroids. Previously exposed patients are eligible following a wash-out period ≥4 weeks before randomisation.
Current need for denosumab therapy. (Patients under bisphosphonate treatment are eligible).
Skin disease interfering with evaluation of local tolerance of GX301 injections.
Any condition which, in the judgment of the Investigator, would place the subject at undue risk or interfere with the results of the study.
Inability to regularly access centre facilities for logistical or other reasons.
Participation in any interventional drug or medical device study within 30 days prior to treatment start. |
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E.5 End points |
E.5.1 | Primary end point(s) |
proportion of patients achieving immunological response:
A panel of three immunological tests will be performed on blood samples taken at baseline and on Days 90 and 180 (or upon trial discharge if earlier than on Day 180). All tests will be performed at the central immunology laboratory. Operators will be unaware of the GX301 regimen assigned to each patient.
Immunological tests will be as follows: Elispot assay; intracellular staining and flow cytometry (for both CD4+ and CD8+ T cells); cytotoxic assay.
The immunological outcome of each patient will be represented by a 6-response matrix including positive responses, either absent at baseline or greater than twice the baseline, achieved in the three tests at Days 90 and 180. The outcome will be scored as the sum of positive responses in the matrix (score range: 0 to 6).
Patients will be classified as immunological responders if achieving a score ≥3. Assessable patients will be those in whom ≥3 positive responses or ≥4 negative responses have been shown. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Time-course of PSA (central laboratory).
Maximum PSA change from baseline occurring at any time of the observation period.
Changes from baseline in cancer-related symptoms, FACT-P functional assessment and consumption of analgesic drugs.
Time from randomisation to disease progression (progression-free survival).
Time from randomisation to patient death (overall survival), as derived from on-study and follow-up data. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.8.1.1 | Randomised | Yes |
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 | Yes |
E.8.2.3.1 | Comparator description |
three treatment regimens of the same IMP are tested |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 20 |
E.8.5 | The trial involves multiple Member States | No |
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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the trial ends with a follow up scheduled for week 104 / day 720. this does not imply a visit of the subject, but a contact to assess the vital status. the last subject last visit (LSLV) will be performed at week 78 / day 540. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |