Symptomatic Treatment With Lanreotide Microparticles in Inoperable Bowel Obstruction Resulting From Peritoneal Carcinomatosis: A Randomized, Double-Blind, Placebo-Controlled Phase III Study

2012 ◽  
Vol 30 (35) ◽  
pp. 4337-4343 ◽  
Author(s):  
Pascale Mariani ◽  
Joëlle Blumberg ◽  
Alain Landau ◽  
Daniela Lebrun-Jezekova ◽  
Estelle Botton ◽  
...  
Keyword(s):  
Peritoneal Carcinomatosis ◽  
Bowel Obstruction ◽  
Well Being ◽  
Symptomatic Treatment ◽  
Phase Iii ◽  
Primary Analysis ◽  
Open Label ◽  
Double Blind ◽  
Parallel Group ◽  
Intent To Treat

Purpose To investigate the somatostatin analog lanreotide as symptomatic treatment for inoperable bowel obstruction due to peritoneal carcinomatosis. Patients and Methods In all, 80 patients with peritoneal carcinomatosis, inoperable malignant digestive obstruction, and two or more vomiting episodes per day or nasogastric tube (NGT) who were previously treated with intravenous corticosteroids and proton pump inhibitors were randomly assigned to one 30-mg injection of lanreotide microparticles (n = 43) or placebo (n = 37) in a 10-day, double-blind, parallel-group phase. The primary end point was the proportion of patients responding on day 7 (one or fewer episodes of vomiting per day or no vomiting recurrence after NGT removal [for ≥ 3 consecutive days in both cases]). Vomiting frequency/NGT secretion volumes, nausea, abdominal pain, well-being, and safety were also assessed. Patients could then enter an open-label lanreotide-only phase. The study was conducted at 22 European hospitals. Results More patients receiving lanreotide than placebo were responders; this difference was not statistically significant for the intent-to-treat (ITT) population on the basis of diary cards (primary analysis; 41.9% [18 of 43] v 29.7% [11 of 37], respectively; odds ratio, 1.75; 95% CI, 0.68 to 4.49; P = .24) but was statistically significant for the corresponding supportive per protocol analysis (57.7% [15 of 26] v 30.4% [seven of 23]; P < .05) and ITT analysis, on the basis of investigators' assessments (50.0% [19 of 38] v 28.6% [10 of 35]; P < .05). Improvements in well-being were significantly greater with lanreotide on days 3, 6, and 7. No significant differences were observed for other secondary end points. Only two (mild/moderate) treatment-emergent adverse events were considered related to lanreotide. Conclusion These results show that lanreotide has some efficacy and is safe in the symptomatic treatment of patients with inoperable bowel obstruction due to peritoneal carcinomatosis.

Analysis of the effect of crossover from placebo (PBO) to darolutamide (DARO) on overall survival (OS) benefit in the ARAMIS Trial.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 240-240
Author(s):  
Neal D. Shore ◽  
Karim Fizazi ◽  
Teuvo Tammela ◽  
Murilo Luz ◽  
Manuel Philco Salas ◽  
...  
Keyword(s):  
Treatment Effect ◽  
Safety Profile ◽  
Final Analysis ◽  
Phase Iii ◽  
Sensitivity Analyses ◽  
Primary Analysis ◽  
Open Label ◽  
Double Blind ◽  
Secondary Endpoints ◽  
The Impact

240 Background: DARO is a structurally distinct androgen receptor inhibitor approved for the treatment of non-metastatic castration-resistant prostate cancer (nmCRPC) based on significantly prolonged metastasis-free survival compared with PBO (median 40.4 vs 18.4 months; hazard ratio [HR] 0.41; 95% confidence interval [CI] 0.34–0.50; P < 0.0001) and a favorable safety profile in the phase III ARAMIS trial. Following unblinding at the primary analysis, crossover from PBO to DARO was permitted for the subsequent open-label treatment phase. Sensitivity analyses were performed to assess the effect of PBO–DARO crossover on OS benefit. Methods: Patients (pts) with nmCRPC receiving androgen deprivation therapy were randomized 2:1 to DARO (n = 955) or PBO (n = 554). In addition to OS, secondary endpoints included times to pain progression, first cytotoxic chemotherapy, first symptomatic skeletal event, and safety. The OS analysis was planned to occur after approximately 240 deaths, and secondary endpoints were evaluated in a hierarchical order. Iterative parameter estimation (IPE) and rank-preserving structural failure time (RPSFT) analyses were performed as pre-planned sensitivity analyses to adjust for the treatment effect of PBO–DARO crossover. The IPE method used a parametric model for the survival times and iteratively determined the model parameter describing the magnitude of the treatment effect, whereas a grid search and non-parametric log-rank test were used for the RPSFT analysis. The IPE and RPSFT analyses both generated a Kaplan–Meier curve for the PBO arm that predicts what would have been observed in the absence of PBO–DARO crossover. Results: After unblinding, 170 pts (30.7% of those randomized to PBO) crossed over from PBO to DARO; median treatment duration from unblinding to the final data cut-off was 11 months. Final analysis of the combined double-blind and open label periods was conducted after 254 deaths (15.5% of DARO and 19.1% of PBO pts) and showed a statistically significant OS benefit for DARO vs PBO (HR 0.69; 95% CI 0.53–0.88; P = 0.003). Results from the IPE (HR 0.66; 95% CI 0.51–0.84; P < 0.001) and RPSFT (HR 0.68; 95% CI 0.51–0.90; P = 0.007) analyses were similar to those from the intention-to-treat population, showing that the impact of PBO–DARO crossover was small. Additional analyses accounting for the effect of PBO–DARO crossover will be presented. The safety profile of DARO continued to be favorable at the final analysis, and discontinuation rates at the end of the double-blind period remained unchanged from the primary analysis (8.9% with DARO and 8.7% with PBO). Conclusions: Early treatment with DARO in men with nmCRPC is associated with significant improvement in OS regardless of pts crossing over from PBO to DARO. The safety profile of DARO remained favorable at the final analysis. Clinical trial information: NCT02200614.

scholarly journals Long-Term Efficacy and Safety of Liquid Abobotulinumtoxina Formulation for Moderate-To-Severe Glabellar Lines: A Phase III, Double-Blind, Randomized, Placebo-Controlled and Open-Label Study

2021 ◽  
Author(s):  
Philippe Kestemont ◽  
Said Hilton ◽  
Bill Andriopoulos ◽  
Inna Prygova ◽  
Catherine Thompson ◽  
...  
Keyword(s):  
Patient Satisfaction ◽  
Neutralizing Antibodies ◽  
Well Being ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Open Label ◽  
Double Blind ◽  
Term Efficacy ◽  
Patient Reported

Abstract Background A ready-to-use liquid formulation of abobotulinumtoxinA (aboBoNT-A solution) has been developed. Objectives To assess long-term efficacy and safety of aboBoNT-A solution for glabellar lines (GL) treatment. Methods Multicenter, multinational, Phase III study (NCT02493946), with randomized double-blind placebo-controlled (DBPC; 2:1 aboBoNT-A solution 50 U: placebo) and open-label (OL; 4 cycles aboBoNT-A solution) periods; additional patients were recruited into the OL period. Patients were 18-65 years old; BoNT-naïve; dissatisfied/very dissatisfied with moderate/severe GLs at maximum frown. Investigator’s live assessment (ILA; primary endpoint)/subject’s self-assessment (SSA) of GL severity at maximum frown, patient satisfaction with GL appearance, and FACE-Q patient-reported scales (facial appearance overall, psychological well-being, aging) were assessed. Adverse events (AEs) were monitored. Analyses were performed on DBPC and long-term analysis (LTA; all patients receiving ≥ aboBoNT-A solution injection) populations. Results Mean ages of patients were 46.6–47.8 years, and 89.1–91.3% were female, across DBPC (N=190 [n=126 aboBoNT-A solution, n=64 placebo]) and LTA (N=595) populations. Responder rates for ILA, SSA and patient satisfaction were consistent at Day 29 post-injection across repeat LTA cycles (82.2–87.8%, 62.8–80.6% and 72.2–87.8%, respectively), with statistically significantly higher responder rates versus placebo (DBPC cycle; 81.6% versus 0.8%, 68.1% versus 2.3% and 83.1% versus 5.7%, respectively; all p&lt;0.0001). Consistent improvements on FACE-Q scales occurred with repeat cycles (aboBoNT-A solution versus placebo, p&lt;0.0001 [DBPC cycle]). No new or unexpected AEs, or neutralizing antibodies were observed. Conclusions Results support long-term efficacy and safety of aboBoNT-A solution, and its superiority over placebo, for GL treatment in adults.

Baseline demographics of the randomized, placebo-controlled, double-blind, phase III RADIANT-4 study of everolimus in nonfunctional gastrointestinal (GI) or lung neuroendocrine tumors (NET).

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 276-276 ◽  
Author(s):  
James C. Yao ◽  
Roberto Buzzoni ◽  
Carlo Carnaghi ◽  
Nicola Fazio ◽  
Simron Singh ◽  
...  
Keyword(s):  
Malignant Tumors ◽  
Performance Status ◽  
Progression Free Survival ◽  
The Body ◽  
Neuroendocrine Cells ◽  
Phase Iii ◽  
Somatostatin Analogue ◽  
Primary Analysis ◽  
Open Label ◽  
Double Blind

276 Background: NET are malignant tumors arising from neuroendocrine cells throughout the body. Everolimus (EVE), a mammalian target of rapamycin inhibitor, is approved for the treatment of advanced, well-differentiated pancreatic NET. There is an unmet medical need in GI and lung NET; targeted therapies, such as everolimus, are of particular interest. Methods: Patients with advanced nonfunctional NET of GI or lung origin with progressive disease (PD) within the past 6 months were randomized (2:1) to EVE 10 mg/d or placebo, both with best supportive care. Concomitant use of somatostatin analogue (SSA) was not allowed during the study, except for control of emergent carcinoid symptoms not manageable by standard therapy. Patients were stratified based on tumor sites, prior SSA exposure, and WHO performance status (PS) at baseline. Primary endpoint was progression-free survival (PFS) as assessed by central radiology review using modified RECIST 1.0 criteria. Primary analysis is planned after ~176 PFS events. Crossover to open label EVE after progression would not be allowed prior to the primary analysis. Overall survival was the key secondary endpoint. Results: Recruitment is completed. Of 388 patients screened, 302 were randomized (planned, 285). Median age was 63 years, 53% were females, and majority of them (76.2%) were white. The most common tumor sites were lung (29.8%), ileum (23.5%), and rectum (13.2%). WHO PS was 0 in 219 (72.5%) patients and 1 in 82 (27.2%) patients; 52% had received SSA prior to study entry. As of Sep 16, 2013, 173 (57.3%) patients remain on treatment, 127 (42.1%) discontinued treatment and 2 (0.7%) were not treated. PD (24.2%) and adverse events (10.6%) were the most common reasons for treatment discontinuation. Results of primary analysis are expected by early 2015. Conclusions: RADIANT-4 is the first phase III study to assess the efficacy and safety of EVE in patients with nonfunctional NET of GI or lung origin. Non-crossover design and prospective stratification of the population based on known prognostic factors should minimize confounding in the estimation of the treatment effect. Clinical trial information: NCT01524783.

scholarly journals The Efficacy and Safety of Bilastine in the Treatment of Perennial Allergic Rhinitis in Patients with Moderate and Severe Forms of the Disease. Comparison of bilastine 20 mg with desloratadine 5 mg Сергей

2019 ◽  
pp. 58-67
Author(s):  
S. Ryazantsev ◽  
I. Gogunska ◽  
I. Lymar ◽  
L. Romanyuk ◽  
B. Bil ◽  
...  
Keyword(s):  
Symptomatic Treatment ◽  
Phase Iii ◽  
Comparable Efficacy ◽  
Open Label ◽  
Prick Test ◽  
Treatment Groups ◽  
Persistent Symptoms ◽  
Parallel Group ◽  
Significant Difference ◽  
Rhino Conjunctivitis

Background: Bilastine is a new non-sedating H1 antihistamine approved for the symptomatic treatment of allergic rhinoconjunctivitis (ARC) and urticaria in adults and children over 12 years of age. In this paper, bilastine was compared with desloratadine in the treatment of various forms of allergic rhino-conjunctivitis classified according to the ARIA recommendations.Materials and Methods: This was an international, multi-centre, open-label, prospective randomized, parallel-group, phase III study which enrolled a total of 226 patients with ARC. The diagnosis of the allergic rhino-conjunctivitis was established on the basis of nasal and non-nasal symptoms and confirmed by the skin prick test. Patients were randomized to one of the two treatment groups: bilastine 20 mg daily or desloratadine 5 mg daily.Results: The results for the primary and secondary endpoints showed a comparable reduction in TSS, NSS, and NNSS from the baseline to the end of the treatment between the treatment groups, with slightly better effects for bilastine. Additional tests carried out in the subgroup of patients with moderate / severe persistent (MSP) ARC demonstrated comparable results for the bilastine and desloratadine groups regarding the mean change in TSS from the baseline until the 28th day, except for the sneezing score, for which bilastine showed the higher response (-1.60 ± 0.60 vs. -1.39 ± 0.63), and a statistically significant difference between the treatment groups regarding AUC for TSS ( -26.07 [95% CI: -48.6, -3.53] p = 0.024), NNSS (-10.51 [95% CI:-19.42, -1.59] p = 0.021), the sneezing score (-4.79 [95% CI:-9.06, -0.51] p = 0.028) and the ocular redness score (-5.50 [95% CI: -8.91, -2.08] p = 0.02).Conclusion: In general, bilastine and desloratadine showed a comparable efficacy profile in the treatment of ARC; however, the results obtained in the subgroup of patients with moderate / severe persistent symptoms indicate that bilastine has a stronger therapeutic effect 

Multicenter, randomized, double-blind, ondansetron (ond)-controlled, dose-ranging, parallel group trial of the neurokinin-1 receptor antagonist (NK-1 RA) casopitant mesylate for chemotherapy-induced nausea/vomiting (CINV) in patients (pts) receiving moderately emetogenic chemotherapy (MEC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 8512-8512 ◽  
Author(s):  
W. Arpornwirat ◽  
I. Albert ◽  
V. L. Hansen ◽  
M. A. Russo ◽  
G. A. Ross ◽  
...  
Keyword(s):  
Complete Response ◽  
Trend Test ◽  
Primary Analysis ◽  
Double Blind ◽  
Positron Emission ◽  
Primary Endpoints ◽  
Parallel Group ◽  
Armitage Trend Test ◽  
Neurokinin 1 ◽  
Intent To Treat

8512 Background: Casopitant mesylate is a potent, selective, oral NK-1 RA, which has shown activity in preventing CINV in preclinical studies. Based on phase I positron emission tomography (PET) studies, casopitant doses from 50–150 mg result in 70–95% saturation of NK-1 receptors. This phase II trial evaluated the addition of casopitant to standard prophylaxis (ond + dexamethasone [dex]) in pts receiving MEC. Methods: MEC regimens included ≥ 1 of the following (in mg/m2): cyclophosphamide (ctx) 500–1,500 with other MEC; ctx alone 750–1,500; oxaliplatin ≥ 85; doxorubicin ≥ 60; epirubicin ≥ 90; or carboplatin AUC ≥ 5. Pts were stratified by gender and taxane use. Pts in the first 5 arms received ond 8 mg BID days (D) 1–3 + dex 8 mg IV D1 with either placebo, casopitant 50 mg QD D1–3, casopitant 100 mg QD D1–3, casopitant 150 mg QD D1–3, or casopitant 150 mg D1. Arm 6 received a different ond regimen (16 mg QD D1–3) + dex 8 mg IV D1 + casopitant 150 mg QD D1–3. Primary endpoints were rates of complete response (CR [no vomiting, retching, rescue meds or premature withdrawal]) and no significant nausea (SN, assessed by visual analogue scale) during the first 120 h after initiation of MEC. Arms 5/6 were exploratory and not included in primary analysis. Planned enrollment was 118 pts/arm for intent-to-treat (ITT) analysis. Results: ITT group includes 719 pts (60% male, 40% female). CR rate (120h) was 70% with ond control; 81% for casopitant 50mg; 79% for 100mg; and 85% for 150mg (p=.012, Cochran-Armitage trend test). CR rates (24h) and no SN (120h) were similar among all groups. CR and no SN rates in the exploratory arms were 80% and 66%, respectively, in arm 5 and 84% and 70% in arm 6. Adverse events were similar across all arms, with nausea, fatigue, and neutropenia (≤ 24%) as most common. All casopitant doses were generally well tolerated. Conclusions: Casopitant demonstrated activity in control of CINV at all doses, with the 1-day dose of particular interest, when added to a standard ond + dex regimen in both male and female pts receiving a variety of MEC regimens. [Table: see text]

Efficacy of lanreotide 30 mg as symptomatic treatment in patients with inoperable bowel obstruction due to peritoneal carcinomatosis: A randomized double-blind, placebo-controlled study.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 242-242 ◽  
Author(s):  
P. Mariani ◽  
J. Blumberg ◽  
L. Chauvenet
Keyword(s):  
Peritoneal Carcinomatosis ◽  
Bowel Obstruction ◽  
Response Rate ◽  
Clinical Symptoms ◽  
Group Analysis ◽  
Well Being ◽  
Controlled Study ◽  
Concomitant Treatment ◽  
Double Blind ◽  
Significant Difference

242 Background: Somatostatin analogues in previous open label studies improved symptoms due to bowel obstruction in patients with peritoneal carcinomatosis. This study assessed the efficacy and safety of lanreotide microparticles 30 mg as treatment of clinical symptoms in inoperable patients. Methods: Eighty cancer patients with inoperable digestive obstruction of malignant origin (mean age 62.3 years, 82.5% female) were randomized to receive one intramuscular injection either of lanreotide microparticles 30 mg (N=43) or placebo (N=37). The primary location of cancer was mostly genital (ovary 37.5%, uterus 13.8%) or digestive (colon 16.3%, stomach 11.3%, pancreas 6.3%). Most patients were fed by central parenteral route (80%) and were severely impaired (63.8% ECOG 3 or 4). The primary endpoint was the response rate at day 7 (responders defined as patients with ≤ 1 vomiting episode per day or no vomiting recurrence after removal of the NGT, for at least 3 consecutive days) assessed in a diary card in the intention to treat (ITT) population. Per protocol (PP) population mainly excludes concomitant treatment and inclusion criteria deviations defined during a blinded data review meeting. Results: In the ITT analysis, 41.9% of lanreotide 30mg treated patients were responders versus 29.7% for placebo. This difference was not statistically significant (odds ratio (OR) = 1.75 (95% CI [0.68; 4.49], p = 0.24, logistic regression). The predefinedPP (n= 49) sub group analysis did show a statistically and clinically significantly higher response rate in the lanreotide group (OR 3.60 (95% CI [1.03, 12.62], p = 0.045). There was no significant difference between the 2 treatment groups in secondary efficacy endpoints assessment but there were significant differences in favor of lanreotide in well-being using a visual analogue scale at D3 (p = 0.04), D6 (p = 0.04) and D7 (p = 0.01). No drug-related serious adverse event (SAE) or unexpected event was reported. Conclusions: Lanreotide 30 mg may decrease clinical symptoms and improve well-being in patients with inoperable bowel obstruction due to peritoneal carcinomatosis. [Table: see text]

Sign in / Sign up

Export Citation Format

Share Document