E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Male diseases of the urinary and reproductive systems [C12] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10007113 |
E.1.2 | Term | Cancer of prostate |
E.1.2 | System Organ Class | 100000004864 |
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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 is to investigate whether a vaccination regimen with multiple subcutaneous (SC) administrations of RV001 Vaccine 0.1 mg/mL (RV001V) can reduce prostate-specific antigen (PSA) progression compared to the control group. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are:
- To evaluate the safety and tolerability of RV001 Vaccine 0.1 mg/mL (RV001V) following SC administrations to patients who have a biochemical relapse following definitive local therapy prostatectomy or radiation therapy due to prostate cancer.
- To evaluate whether the vaccination regimen can delay the time to subsequent antineoplastic therapy initiation and substantiate other clinical benefits compared to the control group. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Men aged 18 and above with an earlier histologic diagnosis of prostatic adenocarcinoma.
2. Able to understand the study procedures and willing to provide IC.
3. Able and willing to comply with study requirements and complete all visits.
4. Biochemical recurrence (BCR) in compliance with the following 3 conditions:
-after having finished last definitive treatment (including those who have received RP/RT followed by any modality of salvage therapy),
-no distant metastasis by standard CT imaging with bone scintigraphy or a normal PET-CT and
-no locoregional recurrence (including lymph nodes). Locoregional recurrence will be assessed by multi-parametric magnetic resonance imaging (MRI) in all patients treated with curative RT and should be confirmed with image guided prostatic gland biopsy in case of suspicious lesions. Any prostatic biopsy performed should be negative.
5. Prior definitive treatment with RP or RT. In case the patient was subjected to a RP, all the following will apply:
a. PSA ≥0.2 ng/mL,
b. PSA Doubling Time (PSADT)a >3 months and <12 months,
c. History of Gleason 7 (4 + 3) or higher.
Conversely, if the patient was treated with definitive RT and not prior RP, all the following will apply:
a. PSA >nadira + 2 ng/mL,
b. PSADTa >3 months and <12 months,
c. History of Gleason score of 7 (4 + 3) or higher.
6. Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
7. Laboratory values obtained ≤30 days prior to first vaccination
a. Hemoglobin ≥5.6 mmol/L (0.72 g/L)
b. Absolute granulocyte count ≥1.5 x 109 /L.
c. Platelets ≥100 x 109 /L.
d. Total bilirubin ≤1.5 x upper limit of normal (ULN).
e. Creatinine ≤1.5 x ULN.
f. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) ≤2.5 x ULN.
aNote: Instructions for PSADT calculation: All PSA values used in the calculation should be ≥0.20 ng/ml and follow a rising trend. PSA values need not be consecutively rising and all values obtained over a maximum period of 12 months should be included in the calculation. The maximum period of the past 12 months is recommended to reflect the patient’s current disease activity, since in some men PSADT may change over time. Minimum requirements for the calculation are 3 PSA values obtained over 3 months with a minimum of 4 weeks between measurements. For PSADT calculation after prior RT: A nadir subtraction approach will be applied, wherein the nadir PSA concentration, defined as the lowest PSA value observed following RT, is subtracted from the post‐RT PSA concentrations before calculating PSADT[1].
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E.4 | Principal exclusion criteria |
1. Patients who are receiving androgen-deprivation therapy (ADT) or considered a candidate for immediate ADT or are candidate to any local therapy according to applicable clinical guidelines or judged by the investigator.
2. Patients who have received prior ADT are not eligible with the exception of those that received ADT ≤36 months in duration and ≥9 months before randomization and administered only in the neoadjuvant/adjuvant setting.
3. Patient is planned for salvage therapy.
4. Castrate level of serum testosterone <50 ng/dL at screening.
5. PSA >10 ng/mL.
6. Small-cell, signet cell and neuroendocrine variants of adenocarcinomas.
7. An active malignancy likely to interfere with protocol treatment or FU.
8. Patients who have undergone major surgery or have had major bleeding within the last month prior to the first vaccination.
9. Prior treatment with any therapeutic cancer vaccine(s).
10. Participants with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization. Inhaled or topical steroids, and adrenal replacement steroid doses >10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
11. History of alcohol or substance abuse within the last 5 years.
12. Patients receiving any investigational drug(s) or treatment within 30 days prior to inclusion in this trial.
13. History of significant autoimmune disease such as Inflammatory Bowel Disease, Systemic Lupus Erythematosus, Ankylosing Spondylitis, Scleroderma, Multiple Sclerosis.
14. Severe medical conditions, such as but not limited to severe asthma/chronic obstructive pulmonary disease (COPD), New York Heart Association (NYHA) grading 3 or above, poorly regulated insulin dependent diabetes, any significant organ damage as judged by the Investigator.
15. Other medications, conditions or laboratory results that in the Investigator's opinion would contraindicate study participation for safety reasons or interfere with the interpretation of study results.
16. History of known allergy/hypersensitivity to any component of the study drug (such as Montanide ISA 51), or intolerance to SC injection.
17. Patients with a prior solid organ / stem cell transplantation
18. Patients with known acquired immunodeficiency disorder (AIDS) or any inherited immunodeficiency disorder
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the study is the time to PSA progression is defined as the time from randomization to doubling of PSA from the baseline value, clinical recurrence or death from any cause, whichever occurs first. The time to doubling will be estimated from a log-linear regression of PSA values as dependent variable and considering time as the independent variable in the model. Estimated time to doubling will be calculating as 1/β where β is the slope of the log- linear regression. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The end-of-treatment is within 30 days after the final dose of study treatment. Follow-up visits will begin 12 weeks after end-of-treatment visit, and then every 12 weeks until the patient reaches primary endpoint, or until primary analysis. When the patient reaches a primary endpoint he will move into extended follow up for safety monitoring until the study is terminated 36 months after first patient’s first injection. |
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E.5.2 | Secondary end point(s) |
•The safety will be evaluated with frequency and severity of adverse events (AEs). The numbers and proportions of patients with any treatment-emergent adverse event (TEAE), and any serious TEAE will be summarized. Immune-related AEs (irAEs) will be reported, evaluated and managed following the procedure detailed in Section 9. Safety monitoring and review.
•Time to initiation of a subsequent antineoplastic therapy.
•Proportion of patients initiating a subsequent antineoplastic therapy.
•PSA doubling time (PSADT) based on uncensored data.
•Proportion of patients showing a PSA response from baseline (50% and 30%, best and at 26 weeks):
a.50% PSA response is defined as a decrease in PSA level of at least 50% (compared to baseline PSA) at 26 weeks (Visit 12) after baseline.
b.30% PSA response is defined as a decrease in PSA level of at least 30% (compared to baseline PSA) at 26 weeks (Visit 12) after baseline.
c.Best PSA response is defined as the proportion of patients who have at least a 30% or 50% decrease in PSA level (compared to baseline PSA) at any time point post-randomization.
•Disease-free survival (DFS) is defined as time from randomization to documented clinical recurrence (distant or local), or death from any cause, censoring at date of last follow-up (FU).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The end-of-treatment is within 30 days after the final dose of study treatment. Follow-up visits will begin 12 weeks after end-of-treatment visit, and then every 12 weeks until the patient reaches primary endpoint, or until primary analysis. When the patient reaches a primary endpoint he will move into extended follow up for safety monitoring until the study is terminated 36 months after first patient’s first injection. |
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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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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 | Yes |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 7 |