scholarly journals MP34-17 A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF ENZALUTAMIDE IN PATIENTS WITH NONMETASTATIC CASTRATION-RESISTANT PROSTATE CANCER: POST HOC ANALYSIS OF PROSPER BY PROSTATE SPECIFIC-ANTIGEN PROGRESSION

2019 ◽  
Vol 201 (Supplement 4) ◽  
Author(s):  
Fred Saad* ◽  
Cora N. Sternberg ◽  
Eleni Efstathiou ◽  
Karim Fizazi ◽  
Katharina Modelska ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Controlled Study ◽  
Castration Resistant Prostate Cancer ◽  
Phase 3 ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Post Hoc Analysis ◽  
Castration Resistant ◽  
Post Hoc

Mixed 20-peptide cancer vaccine in combination with docetaxel and dexamethasone for castration-resistant prostate cancer: A randomized, double-blind, placebo-controlled, phase 2 trial.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 214-214 ◽  
Author(s):  
Masanori Noguchi ◽  
Gaku Arai ◽  
Shin Egawa ◽  
Chikara Ohyama ◽  
Seiji Naito ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Vaccine ◽  
Specific Antigen ◽  
Human Leukocyte ◽  
Phase 2 ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Phase 2 Trial ◽  
Castration Resistant

214 Background: A novel cancer vaccine consisting of 20 mixed peptides (KRM-20) was designed to induce cytotoxic T lymphocytes (CTL) against twelve different tumor-associated antigens. The aim of this phase 2 trial was to examine whether KRM-20 in combination with docetaxel and dexamethasone enhances anti-tumor effects in patients with castration-resistant prostate cancer (CRPC). Methods: In this double-blind, placebo-controlled, randomized, phase 2 study, we enrolled chemotherapy-naïve patients with progressive CRPC from 10 medical centers in Japan. Eligible patients were randomly assigned 1:1 centrally to either KRM-20 combined with docetaxel and dexamethasone or placebo with docetaxel and dexamethasone. Patients initially received 5 weekly subcutaneous KRM-20 (20 mg) or placebo injections with daily oral dexamethasone (1 mg) following 5 courses of docetaxel (70 mg/m2 every 3 weeks). The primary endpoint was to compare each treatment for prostate-specific antigen (PSA) decline. Results: Between Jul 31, 2013 and Jul 11, 2014, 51 patients were enrolled to the trial: 25 were assigned to the KRM-20 arm, and 26 were allocated to the placebo arm. Mean % PSA levels from baseline in the KRM-20 arm significantly decreased during the treatment compared witht those in the placebo arm ( P = 0.028, MANOVA). Human leukocyte antigen matched peptide-specific immunoglobulin G ( P = 0.018) and CTL ( P = 0.007) responses in the KRM-20 arm significantly increased after the treatment. The appearance of myeloid-derived suppressor cells in the KRM-20 arm significantly decreased after the treatment ( P = 0.007). The addition of KRM-20 did not result in increased toxicity. There was no between-group differences in progression-free or overall survival. Conclusions: These findings suggest potential clinical benefits for the combined use of KRM-20 with docetaxel and dexamethasone in patients with CRPC. Clinical trial information: UMIN000011028.

scholarly journals Personalized peptide vaccination for castration-resistant prostate cancer progressing after docetaxel: A randomized, double-blind, placebo-controlled, phase III trial

2020 ◽  
Author(s):  
Masanori Noguchi ◽  
Kiyohide Fujimoto ◽  
Gaku Arai ◽  
Hiroji Uemura ◽  
Katsuyoshi Hashine ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase Iii ◽  
Base Line ◽  
Castration Resistant Prostate Cancer ◽  
Peptide Vaccination ◽  
Phase 3 ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Castration Resistant ◽  
Docetaxel Chemotherapy

Abstract Background To develop a new treatment modality, we conducted a phase 3 randomized trial of personalized peptide vaccination (PPV) for human leukocyte antigen (HLA)-A24-positive patients with castration-resistant prostate cancer (CRPC) for whom docetaxel chemotherapy failed. Methods This randomized, double-blind, placebo-controlled, phase 3 trial was done at 68 medical centers in Japan. Eligible patients were aged 20 years or older, positive immunoglobulin G (IgG) responses to at least 2 of 12 warehouse peptides, an Eastern Cooperative Oncology Group performance status of 0 or 1, life expectancy of at least 12 weeks, serum testosterone level of ≤ 50 ng/dl, and satisfactory bone marrow function, hepatic function, and renal function. Patients were randomly assigned in a 2:1 ratio to receive PPV or placebo. Four of 12 warehouse peptides selected based on pre-existing peptide-specific IgG levels or the corresponding placebo were subcutaneously injected in 6 doses weekly and then bi-weekly following the maximum of 30 doses until disease progression. The primary end point was overall survival (OS). Efficacy analyses were by the full analysis set. Results Between August 2013 and April 2016, 310 patients were randomly assigned, and 306 patients were analyzed. Baseline characteristics were balanced between groups. The estimated median OS was 16.1 months (95% confidence interval [CI], 13–18.2) with PPV and 16.9 months (95% CI, 13.1–20.4) with placebo (hazard ratio [HR], 1.04, 95% CI, 0.80–1.37; p = 0.77). Grade ≥ 3 adverse events were observed in 41% in both groups. The analysis of treatment arm effects among subgroups revealed lower HRs for OS in favor of the PPV arm in patients with < 64% neutrophils (HR, 0.55, 95% CI, 0.33–0.93; p = 0.03) or ≥ 26% lymphocytes (HR, 0.70, 95% CI, 0.52–0.92; p = 0.02) at base line. Conclusions PPV did not prolong OS in HLA-A24-positive patients with CRPC progressing after docetaxel chemotherapy. Subgroup analysis suggested that the patients with a lower proportion of neutrophils or a higher proportion of lymphocytes at base line can receive survival benefits from PPV treatment.

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