Castration-resistant prostate cancer (patients who have achieved response to first-line docetaxel chemotherapy). MedDRA version: 16.1 Level: PT Classification code 10062904 Term: Hormone-refractory prostate cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: MED-GX301-02
Product Code: MED-GX301-02
Pharmaceutical Form: Solution for injection/infusion
Product Name: Montanide ISA 51 VG
Product Code: Montanide ISA 51 VG
Pharmaceutical Form: Emu
Sponsors
Laboratoires Leurquin Mediolanum S.A.S.
Eligibility
Sex/Gender
Male
Inclusion criteria
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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range 120 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 120
Exclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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.;Secondary Objective: • 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.;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.;Timepoint(s) of evaluation of this end point: week 26 / day 180 | — |
Secondary
| Measure | Time frame |
|---|---|
| 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.;Timepoint(s) of evaluation of this end point: up to week 104 / day 720 | — |
Countries
Italy, Spain
Contacts
Public ContactProject Leader
Mediolanum Farmaceutici S.p.A.
Outcome results
None listed