metastatic hormone-sensitive prostate cancer MedDRA version: 20.0 Level: PT Classification code 10036909 Term: Prostate cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: YERVOY 5 mg/ml CONCENTRADO PARA SOLUCION PARA PERFUSION
Product Name: Ipilimumab
Product Code: BMS-734016
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: IP
Sponsors
SOGUG (Spanish Genitourinary Oncologic Group)
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Patients must be at least 18 years of age 2. Signed and dated written informed consent, obtained before the performance of any protocol-related procedure. 3. Histological or cytological diagnosis of prostate cancer with an elevated PSA level and radiologic evidence of metastatic disease. 4. ECOG performance-status score of 0, 1, or 2. Patients with a score of 2 are eligible if the decrement in functioning was due to prostate cancer. 5. Metastatic disease that has spread beyond the prostate or relapsed after local therapy, documented by body CT scan and/or bone scan, according to PCWG 3 criteria, with high volume according to criteria used in the CHAARTED study. 6. Radiological and scintigraphic studies to identify initial evaluable disease should be done as follows: • If ADT has not been initiated, CT scans and bone scan must be obtained within 6 weeks prior to the start of ADT. • If all required imaging had not been completed prior to starting ADT, any additional scan must be obtained after starting androgen deprivation but prior to randomization and the initiation of docetaxel (It is assumed that the scans of patients with high volume disease would not normalize in less than 120 days to the point that a patient would go from “high volume” to “low volume”). 7. Measurable or evaluable disease according to the PWGC 3. 8. Patients who started ADT for metastatic disease are eligible if ADT commenced within 120 days before randomization, they have not started docetaxel chemotherapy yet, and there was no evidence of clinical, radiological or biochemical progression after ADT. 9. Patients receiving ADT in the adjuvant and/or neoadjuvant setting for less than 30 months of therapy, AND the effect of the last depot injection had expired at least 12 months prior to documentation of metastatic disease, AND • They had no evidence of disease (PSA 1500/mm 3 • Platelet count > 100,000/mm 3 • Creatinine clearance (CrCl)> 30 mL/min calculated at screening using the Cockcroft- Gault formula: Creatinine clearance for mule (mL/min) = (140- age in years)(body weight in kg)/[72x(serum creatinine in mg/dl). • Total bilirubin < 1.5 ULN (< 3.0 mg/dl in patients with Gilbert´s Syndrome). • Prothrombin time or INR and PTT < 1.5 x ULN, except if on therapeutic anti- coagulation in which case the patient can be enrolled if stable and anti-coagulation levels are appropriate for their condition per good clinical practice. • ALT and AST < or = 3 x ULN (or < or = 5 if liver metastases) 11. At least 4 weeks should have passed after major surgery prior to randomization, and the patient should be recovered from all side effects and complications. 12. Men who are sexually active with WOCBP must agree to follow instructions for methods of contraception for the duration of treatment with study drug plus 5 half-lives of study drug plus 90 days (duration of sperm turnover) for a total of 31 weeks post-treatment completion. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years)
Exclusion criteria
Exclusion criteria: 1. Patients are not eligible if the PSA has risen from its lowest point, between the beginning of androgen deprivation therapy and the date of randomization, and met criteria for progression as defined in the protocol. 2. Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, PROSTVAC, Sipuleucel-T or any previous immunotherapy or vaccines for cancer. 3. Prior chemotherapy in the adjuvant or neoadjuvant setting. 4. Unable to receive docetaxel at full doses at investigator criteria. 5. Peripheral neuropathy grade > 1. 6. All toxicities attributed to prior anti-cancer therapy other than neuropathy, alopecia or fatigue must have resolved to Grade 1 (NCI CTCAE version 4) or baseline before administration of study drug. Subjects with toxicities attributed to prior surgery or radiotherapy, which are not expected to resolve and result in long-term lasting sequelae, are permitted to enrol. 7. History of hypersensitivity reaction to Docetaxel®, other drugs formulated with polysorbate 80, or monoclonal antibodies. 8. Prior hormone therapy or immunotherapy in the metastatic setting. 9. Prior palliative radiation therapy within 30 days of starting docetaxel. 10. Known acute or chronic HIV, Hepatitis B, or Hepatitis C. Past Hepatitis B infection with no signs of activity later, are allowed 11. Active brain metastases or leptomeningeal metastases, except if they have been treated and there is a magnetic resonance imaging (or CT scan if MRI were contraindicated) showing no evidence of progression for at least 4 weeks after the treatment 12. Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days previous to randomization. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. 13. Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are allowed. 14. Active cardiac disease defined as active angina, symptomatic congestive heart failure, or myocardial infarction within the previous six months 15. History of malignancy in the past 5 years except for basal cell and squamous cell carcinoma of the skin and non-muscle-invasive bladder cancer. Other more malignancies considered to have a low potential to progress may be enrolled if approved by study chair. 16. Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results. 17. Participation in another clinical trial within 30 days prior to randomization.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: whole objective: To evaluate if an addition of immunotherapy or other therapies to the standard treatment of ADT plus chemotherapy improves the overall survival [expressed as the hazard ratio (HR) of death between the experimental (E) and the control arm (C)] of patients with non-castrate high volume metastatic prostate cancer. Primary objectives of the pilot phase: • To assess the feasibility and toxicity of the new experimental arms (immunotherapy or other therapies plus ADT and docetaxel), by describing the incidence of expected and unexpected severe toxicities and adverse events/reactions. • To analyse the feasibility and applicability of immune-RECIST (iRECIST) criteria of response and progression for metastatic prostate cancer, within the concept of “clinical progression-free survival (PFS)” and “time to castration resistant prostate cancer (CRPC)”;Secondary Objective: Comparison among experimental arms and control arms of several endpoints;Primary end point(s): Overall Survival;Timepoint(s) of evaluation of this end point: Through the study and after treatment in the follow-up period | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. PSA response. 2. PSA progression-free survival (PSA-PFS). 3. Radiological progression-free survival (rPFS). 4. Clinical progression-free survival (cPFS). 5. Time to castration resistant prostate cancer (TCRPC). 6. Immune radiological progression-free survival (irPFS). 7. Immune clinical progression-free survival (icPFS). 8. Time to immune castration resistant prostate cancer (TiCRPC). 9. Symptomatic skeletal-related event free survival (SSREFS). 10. Toxicity 11. Quality of life (QOL).;Timepoint(s) of evaluation of this end point: Through the study and after treatment in the follow-up period | — |
Countries
Spain
Contacts
Public ContactSecretaría SOGUG
SOGUG (Spanish Genitourinary Oncologic Group)
Outcome results
None listed