Final analysis of relapse-free survival in a multicenter, double-blind, placebo-controlled trial of seviprotimut-L polyvalent melanoma vaccine after resection of high-risk melanoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 10017-10017
Author(s):  
Craig L. Slingluff ◽  
Brent A. Blumenstein ◽  
Karl D. Lewis ◽  
Robert Hans Ingemar Andtbacka ◽  
John Robert Hyngstrom ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Controlled Trial ◽  
Hazard Ratio ◽  
Phase Iii ◽  
P Value ◽  
Relapse Free Survival ◽  
Support Design ◽  
Double Blind ◽  
Free Survival ◽  
Double Blind Placebo

10017 Background: Seviprotimut-L is a vaccine prepared from antigens of 3 human melanoma cell lines, administered with alum. Prior formulations induced T cell and antibody responses and improved survival in a small phase II clinical trial. Part B1 of MAVIS (Melanoma Antigen Vaccine Immunotherapy Study, a three part, Phase III clinical program), was a multicenter, double-blind, placebo-controlled trial to assess efficacy of seviprotimut-L, with the primary endpoint of relapse-free survival (RFS). The goal of Part B1 was to guide design of the pivotal Part B2. Methods: Patients with AJCC v7 stage IIB-III cutaneous melanoma, after surgical resection, age 18-75, ECOG PS 0-1, were randomized 2:1 to seviprotimut-L 40 mcg or placebo, injected subcutaneously every 2 weeks x 5, then monthly x 4, then every 3 months x 9. Patients were stratified by stage (IIB/C, IIIA, IIIB/C). Target enrollment was 325. The study was powered for assessment of RFS, with target hazard ratio (HR) of 0.625, one-sided alpha of 0.10, and power 80%. Final data are presented. Results: 347 patients were randomized. Arms were well-balanced. Treatment-related adverse events (AEs) led to discontinuation in 0.4% and 0%, respectively, for vaccine and placebo arms. There were no treatment-related SAEs. By intent-to-treat (ITT) analysis, RFS was not significantly longer for seviprotimut-L in the full study population but trended toward benefit (HR 0.88). Subgroup analysis based on planned stratification revealed the hazard ratio (HR) for the Stage IIB/IIC subset (randomization stratum, n=111) to be 0.65 (95% CI [0.37, 1.17]), favoring seviprotimut-L. Age can decrease immune competence: RFS was longer with vaccine for patients age <60 overall (N = 191, HR = 0.64 [0.38, 1.08]) and among Stage IIB/C patients (N = 52, HR = 0.32 [0.12, 0.86]). The effect modification interaction p value for age for stage IIB/IIC patients was 0.056. In a multivariable RFS model, for IIB/IIC patients <60 with ulceration (n=38), HR = 0.209 [0.07,0.61]. For overall survival, for patients < 60, HR = 0.41 [0.33,1.14] (n=191, 19 deaths) and for those ≥60, HR = 0.92 [0.39,2.12] (n = 156, 24 deaths). Conclusions: Seviprotimut-L is very well-tolerated. Subgroup efficacy analyses identified populations who may benefit from Seviprotimut-L: those with Stage IIB/IIC melanoma and those under age 60. These data support design of the definitive part B2 of the MAVIS phase III trial to test seviprotimut-L for stage IIB/C patients, with stratification by age and ulceration. Clinical trial information: NCT01546571.

FLORA-5: Front-line chemoimmunotherapy (Paclitaxel-Carboplatin-Oregovomab [PCO] versus chemotherapy (Paclitaxel-Carboplatin-Placebo [PCP]) in patients with advanced epithelial ovarian cancer (EOC)—Phase III double-blind placebo controlled multinational study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS5606-TPS5606
Author(s):  
Angeles Alvarez Secord ◽  
Sunil Gupta ◽  
Cathy Reddick ◽  
Jyoti Chauhan ◽  
Sarah Gill ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Antigen Processing ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Target Antigen ◽  
Controlled Clinical Trial ◽  
Front Line ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Post Surgery

TPS5606 Background: Oregovomab binds tumor-associated CA125 rendering the target antigen CA125 more immunogenic or “neoantigen-like” through altered and enhanced antigen processing and presentation to specific T cells. This phenomenon is hypothesized to bypass tumor-associated immune suppression when administered in combination with chemotherapy. In a randomized phase II study, immunization with oregovomab in a schedule-dependent combination with paclitaxel and carboplatin induced tumor immunity and demonstrated significant improvement in PFS (median (months) 41.8 PCO vs 12.3 PCP, HR 0.44 p = 0.0027, and OS median N.E. PCO vs 43.2 PCP HR O.34 (p = 0.0077)) in patients with previously untreated EOC. The FLORA-5, the definitive confirmatory global registration trial, is currently recruiting patients in the front-line setting. Methods: The study is a phase 3, multicenter, double-blind, placebo-controlled clinical trial. Optimally debulked patients with FIGO III/IV EOC and serum CA125 > 50 U/ml receiving adjuvant (Cohort 1) or neoadjuvant (Cohort 2) chemotherapy will be randomized post-surgery to paclitaxel and carboplatin with or without oregovomab. Patients with germline BRCA1/2 mutations will be excluded. Chemotherapy will be administered every 3 weeks in both cohorts. Oregovomab/placebo is administered simultaneously at cycles 1, 3, and 5 of chemotherapy with a single maintenance dose at 12 weeks following cycle 5 in Cohort 1. Neoadjuvant patients (Cohort 2) will be administered oregovomab/placebo post interval debulking surgery at cycles 4 and 6 with maintenance doses at 6- and 18-weeks following cycle 6. No other post front-line maintenance therapy is permitted. The primary objective is PFS determined by RECIST 1.1 criteria. Cohort 1 will recruit 372 patients with a 90% power to detect a difference with an alpha of 0.025 and a hazard ratio of 0.65 when 252 PFS events have been observed. Cohort 2 will be analyzed separately recruiting 232 patients with a 90% power to detect a difference with an alpha of 0.025 and a hazard ratio of 0.60 when 165 PFS events have been observed. An interim analysis for futility will be performed. Secondary objectives include OS, frequency and severity of adverse events, and quality of life. Exploratory objectives include iRECIST, TFST, TSST, PFS2, and evaluation of potential biomarkers. The study is actively enrolling in the US with 9 patients enrolled at time of submission. Centers in Europe, South America and Asia are expected to begin accruing shortly. Clinical trial information: NCT04498117.

scholarly journals A 36-week multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3 clinical trial of sodium oligomannate for mild-to-moderate Alzheimer’s dementia

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Shifu Xiao ◽  
Piu Chan ◽  
Tao Wang ◽  
Zhen Hong ◽  
Shuzhen Wang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trial ◽  
Controlled Trial ◽  
Drug Effects ◽  
Disease Assessment ◽  
Phase 3 ◽  
Double Blind ◽  
Double Blind Placebo ◽  
The Difference

Abstract Background New therapies are urgently needed for Alzheimer’s disease (AD). Sodium oligomannate (GV-971) is a marine-derived oligosaccharide with a novel proposed mechanism of action. The first phase 3 clinical trial of GV-971 has been completed in China. Methods We conducted a phase 3, double-blind, placebo-controlled trial in participants with mild-to-moderate AD to assess GV-971 efficacy and safety. Participants were randomized to placebo or GV-971 (900 mg) for 36 weeks. The primary outcome was the drug-placebo difference in change from baseline on the 12-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog12). Secondary endpoints were drug-placebo differences on the Clinician’s Interview-Based Impression of Change with caregiver input (CIBIC+), Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale, and Neuropsychiatric Inventory (NPI). Safety and tolerability were monitored. Results A total of 818 participants were randomized: 408 to GV-971 and 410 to placebo. A significant drug-placebo difference on the ADAS-Cog12 favoring GV-971 was present at each measurement time point, measurable at the week 4 visit and continuing throughout the trial. The difference between the groups in change from baseline was − 2.15 points (95% confidence interval, − 3.07 to − 1.23; p < 0.0001; effect size 0.531) after 36 weeks of treatment. Treatment-emergent adverse event incidence was comparable between active treatment and placebo (73.9%, 75.4%). Two deaths determined to be unrelated to drug effects occurred in the GV-971 group. Conclusions GV-971 demonstrated significant efficacy in improving cognition with sustained improvement across all observation periods of a 36-week trial. GV-971 was safe and well-tolerated. Trial registration ClinicalTrials.gov, NCT02293915. Registered on November 19, 2014

Lithium vs valproate in the maintenance treatment of bipolar I disorder: A post- hoc analysis of a randomized double-blind placebo-controlled trial

2019 ◽  
Vol 54 (3) ◽  
pp. 298-307
Author(s):  
Mehar G Kang ◽  
Hong Qian ◽  
Kamyar Keramatian ◽  
Trisha Chakrabarty ◽  
Gayatri Saraf ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Atypical Antipsychotic ◽  
Maintenance Treatment ◽  
Atypical Antipsychotics ◽  
Controlled Trial ◽  
Hazard Ratio ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Post Hoc Analysis ◽  
Post Hoc

Objective: Lithium and valproate are commonly used either in monotherapy or in combination with atypical antipsychotics in maintenance treatment of bipolar I disorder; however, their comparative efficacy is not well understood. This study aimed to compare the efficacy of valproate and lithium on mood stability either in monotherapy or in combination with atypical antipsychotics. Methods: We performed a post hoc analysis using data from a 52-week randomized double-blind, placebo-controlled trial, that recruited 159 patients with recently remitted mania during treatment with lithium or valproate and adjunctive atypical antipsychotic therapy. Patients were randomized to discontinue adjunctive atypical antipsychotic at 0, 24 or 52 weeks. Results: No significant differences in efficacy were observed between valproate and lithium (hazard ratio: 0.99; 95% confidence interval: [0.66, 1.48]) in time to any mood event. Valproate with 24 weeks of atypical antipsychotic was significantly superior to valproate monotherapy in preventing any mood relapse (hazard ratio: 0.46; 95% confidence interval: [0.22, 0.97]) while lithium with 24 weeks of atypical antipsychotic was superior to lithium monotherapy in preventing mania (hazard ratio: 0.27; 95% confidence interval: [0.09, 0.85]) but not depression. Conclusion: Overall, this study did not find significant differences in efficacy between the two mood-stabilizing agents when used as monotherapy or in combination with atypical antipsychotics. However, study design and small sample size might have precluded from detecting an effect if true difference in efficacy existed. Further head-to-head investigations with stratified designs are needed to evaluate maintenance therapies.

scholarly journals Efficacy of aspirin for stage III colorectal cancer: a randomized double-blind placebo-controlled trial (JCOG1503C, EPISODE-III trial)

2019 ◽  
Vol 49 (10) ◽  
pp. 985-990 ◽  
Author(s):  
Kenichi Miyamoto ◽  
Atsuo Takashima ◽  
Junki Mizusawa ◽  
Yuya Sato ◽  
Yasuhiro Shimada ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Adverse Events ◽  
Curative Resection ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Stage Iii ◽  
Double Blind ◽  
Free Survival ◽  
Double Blind Placebo

Abstract Adjuvant chemotherapy is the current standard treatment for stage III colorectal cancer after curative resection. However, the prognosis of stage III colorectal cancer is still poor even after curative resection and adjuvant chemotherapy. Several observational studies suggested that the anti-tumor effect of aspirin. Therefore, we planned a randomized double-blind placebo-controlled phase III trial, which commenced in Japan in March 2018, to confirm the superiority of aspirin over placebo added to adjuvant chemotherapy in terms of disease-free survival (DFS) for stage III colorectal cancer patients after curative resection. A total of 880 patients will be accrued from 20 Japanese institutions within 3 years. The primary endpoint is DFS and the secondary endpoints are overall survival, relapse-free survival, relative dose intensity, adverse events, and serious adverse events. This trial has been registered at Japan Registry of Clinical Trials as jRCTs031180009 (https://jrct.niph.go.jp/detail/589).

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